Arylquinazolines

Abstract

The invention relates to novel compounds of the formula (I) which can be used for the inhibition of serine-threonine protein kinases and for the sensitization of cancer cells to anticancer agents and/or ionizing radiation.

Claims

1. A compound of formula (III) ##STR00530## in which R.sup.6 is Hal, LA, oxo, CN, NH.sub.2 or Het.sup.2; R.sup.6 is H, Hal, LA, oxo, CN, NH.sub.2 or Het.sup.2; - - - - denotes the presence or absence of double bonds in Cyc; X is CH, CF, S or N, Y is CH, S or N, n is 1 or 2, where if n=1, XS, and if n=2, both XCH, or the X linked to the pyrimidine ring is CF and the X not linked to the pyrimidine ring is CH, or one X is CH and the other X is N; m is 1 or 2, where if m=1, YS, and if m=2, both YCH, or one Y is CH and the other Y is N; R.sup.1 and R.sup.2, independently of one another, are H, Hal, CN, OH, CONH.sub.2, CONH(LA) or LA; R.sup.3 is Hal, CN, OH, CONH.sub.2, CONH(LA) or LA; R.sup.5 is H, Hal, CN or CCH; Cyc is phenyl, which may be mono- or disubstituted, independently of one another, by R.sup.6, or is Het.sup.1; Het.sup.1 is a mono- or bicyclic, 5-10-membered heterocycle, having 1-3 N, O or S atoms, or 1-4 N atoms, which may be mono-, di- or trisubstituted, independently of one another, by R.sup.6, or may be monosubstituted by Het.sup.2; LA is unbranched or branched alkyl having 1-5 C atoms, which may be saturated or partially unsaturated, in which 1-3 H atoms may be replaced by Hal, or one H atom may be replaced by CN or Het.sup.2, or one or two CH.sub.2 groups may be replaced by O, NH, N(CH.sub.3) or CO; Het.sup.2 is a 3-5-membered aliphatic homo- or heterocycle having 0, 1, 2 or 3 N, O or S atoms, which is unsubstituted; and Hal is F, Cl, Br or I; wherein any H, C, N, O, P, F, and Cl can be in the form of a heavier isotope thereof; or physiologically acceptable salts, tautomers or stereoisomers thereof, including mixtures thereof in all ratios.

2. The compound according to claim 1, wherein said compound is of formula (IIIa) ##STR00531## in which R.sup.3 is Hal, CN, OH, CONH.sub.2, CON(LA) or LA; R.sup.6 is Hal, LA, oxo, CN, NH.sub.2 or Het.sup.2; R.sup.6 is H, Hal, LA, oxo, CN, NH.sub.2 or Het.sup.2; X.sup.1 is CH, CF or N; X.sup.2 is CH or N, where X.sup.1, X.sup.2 are not simultaneously N; Y is CH or N; and - - - - denotes the presence or absence of double bonds in Cyc; or physiologically acceptable salts, tautomers or stereoisomers thereof, including mixtures thereof in all ratios.

3. The compound according to claim 1, wherein said compound is of formula (IIIb) ##STR00532## in which R.sup.3 is Hal, CN, OH, CONH.sub.2, CON(LA) or LA; R.sup.6 is Hal, LA, oxo, CN, NH.sub.2 or Het.sup.2; R.sup.6 is H, Hal, LA, oxo, CN, NH.sub.2 or Het.sup.2; Y is CH or N; and - - - - denotes the presence or absence of double bonds in Cyc; or physiologically acceptable salts, tautomers or stereoisomers thereof, including mixtures thereof in all ratios.

4. The compound according to claim 2, in which in the case of sub-formula (IIIa-B) R.sup.1 is F; or in the case of sub-formula (IIIa-C) X.sup.1, X.sup.2 is CH; or in the case of sub-formula (IIIa-D) X.sup.1 is CH, and R.sup.5 is H; or in the case of sub-formula (IIIa-E) R.sup.3 is OH; or in the case of sub-formula (IIIa-F) X.sup.1 is CH, and R.sup.3 is OH; or in the case of sub-formula (IIIa-G) X.sup.1 is CH, and Y is CH; or in the case of sub-formula (IIIa-H) X.sup.1 is CH, and Cyc is pyridine, pyrazine or pyridazine, or pyrazolo[1,5-a]pyrimidinyl or imidazo[1,2-b]pyridazinyl; or in the case of the sub-formula (IIIa-J) Cyc is pyridine, pyrazine, pyridazine, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-b]pyridazinyl, furo[2,3-c]pyridinyl, furo[2,3-d}pyridazinyl, thieno[2,3-d}-pyridazinyl, thieno[2,3-d}pyrimidinyl or imidazo[4,5-c]pyridinyl, each of which may be mono- or disubstituted by methoxy, methyl, oxo, Cl or CHF.sub.2O; or in the case of sub-formula (IIIa-K) R.sup.1 is F or Cl, R.sup.3 is OH, R.sup.5 is H, and X.sup.1, X.sup.2 is CH; or in the case of sub-formula (IIIa-L) R.sup.1 is F, R.sup.3 is OH, and R.sup.5 is H; or in the case of sub-formula (IIIa-M) R.sup.1 is F or Cl, R.sup.3 is OH, R.sup.5 is H, X.sup.1, X.sup.2 is CH, and Cyc is pyridine, pyrazine or pyridazine, or pyrazolo[1,5-a]pyrimidinyl or imidazo[1,2-b]pyridazinyl; or in the case of sub-formula (IIIa-N) R.sup.1 is F, R.sup.3 is OH, R.sup.5 is H, and Cyc is pyridine, pyrazine, pyridazine, pyrazolo[1,5-a]pyrimidinyl, imidazo[1,2-b]pyridazinyl, furo[2,3-c]pyridinyl, furo[2,3-d}pyridazinyl, thieno[2,3-d}-pyridazinyl, thieno[2,3-d}pyrimidinyl or imidazo[4,5-c]pyridinyl, each of which may be mono- or disubstituted by methoxy, methyl, oxo, Cl or CHF.sub.2O; or in the case of sub-formula (IIIa-O) R.sup.1 is F, R.sup.3 is OH, R.sup.5 is H, and Cyc is 5-methoxypyridazin-3-yl, imidazo[1,2-b]pyridazin-6-yl, 3-chloro-6-methoxypyrazin-2-yl, 3-chloropyrazin-2-yl, pyridazin-4-yl, 3-methoxypyrazin-2-yl, 6-methoxypyridazin-3-yl, 3-difluoromethoxypyridin-2-yl, 3-methylpyrazin-2-yl, thieno[2,3-d}pyrimidin-4-yl, 1-methyl-1H-pyridin-2-one-6-yl, 1H-pyridazin-6-one-3-yl, furo[2,3-d}pyridazin-7-yl, thieno[2,3-d}pyridazin-7-yl, 3,5-dimethylpyrazin-2-yl, furo[2,3-d}pyrimidin-4-yl, 3-methyl-3H-imidazo[4,5-c]pyridin-4-yl, or physiologically acceptable salts, tautomers or stereoisomers thereof, including mixtures thereof in all ratios.

5. The compound according to claim 3, in which in the case of sub-formula (IIIb-Q) R.sup.1 is F or Cl, R.sup.3 is OH, R.sup.5 is H, and Y is CH; or in the case of sub-formula (IIIb-R) R.sup.1 is F, R.sup.3 is OH, R.sup.5 is H, and Y is CH; or in the case of sub-formula (IIIb-S) Cyc is pyridine, pyrazine or pyridazine; or in the case of sub-formula (IIIb-T) R.sup.1 is F or Cl, R.sup.3 is OH, R.sup.5 is H, and Cyc is pyridine, pyrazine or pyridazine; or in the case of sub-formula (IIIb-U) R.sup.1 is F, R.sup.3 is OH, R.sup.5 is H, and Cyc is pyridine, pyrazine, pyridazine or 3-methylpyrazin-2-yl; or or physiologically acceptable salts, tautomers or stereoisomers thereof, including mixtures thereof in all ratios.

6. The compound according to claim 1, wherein said compound is selected from the following: (R)-(3-Chloropyrazin-2-yl)-[4-fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]methanol, (R)-[4-Fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(3-methyl pyrazin-2-yl)methanol, (R)-[4-Fluoro-3-(7-morpholin-4-ylpyrido[3,2-d}pyrimidin-4-yl)phenyl]-(3-methylpyrazin-2-yl)methanol, or (R)-[4-Fluoro-3-(5-fluoro-7-morpholin-4-ylquinazolin-4-yl)phenyl]-(3-methylpyrazin-2-yl)methanol; or physiologically acceptable salts, tautomers or stereoisomers thereof, including mixtures thereof in all ratios.

7. A pharmaceutical composition comprising, as active compound, an effective amount of at least one compound according to claim 1 or physiologically acceptable salts, tautomers or stereoisomers thereof, including mixtures thereof in all ratios, together with pharmaceutically tolerated adjuvants.

8. The pharmaceutical composition according to claim 7, further comprising an effective amount of at least one anticancer agent.

9. A kit comprising separate packs of (a) an effective amount of at least one compound according to claim 1 or physiologically acceptable salts, tautomers or stereoisomers thereof, including mixtures thereof in all ratios, and (b) an effective amount of at least one anticancer agent.

Description

EXAMPLES

(1) An overview of the working examples is given by Tables 1-7.

(2) The following ranges apply to the biological data reproduced therein:

(3) DNA-PK (enzymatic):

(4) A: IC.sub.50<3 nM

(5) B: 3 nMIC.sub.50<7 nM

(6) C: 7 nMIC.sub.50<30 nM

(7) D: 30 nMIC.sub.50

(8) pDNA-PK (cellular):

(9) A: IC.sub.50<0.5 M

(10) B: 0.5 MIC.sub.505 M

(11) C: 5 MIC.sub.50<10 M

(12) D: 10 MIC.sub.50<30 M

(13) Kv11.1 hERG:

(14) A: K.sub.i>25 WI

(15) B: 25 MK.sub.i>15 M

(16) C: 15 MK.sub.i>10 M

(17) D: 10 MK.sub.i

(18) Analysis

(19) NMR (.sup.1H) was carried out with the following parameters.

(20) Instruments: Bruker Avance DRX 500, Bruker Avance 400, Bruker DPX 300

(21) Reference: TMS

(22) TD (time domaine=number of data points or digital resolution): 65536

(23) Solvent: DMSO-d6

(24) NS (number of scans=frequency of scanning): 32

(25) SF (spectrometer frequence=transmission frequency): 400 or 500 MHz

(26) TE (temperature): 303 K, 363 K or 393 K

(27) Coupling constants (J) are indicated in hertz (Hz)

(28) HPLC: high performance chromatography with UV detector

(29) LC-MS: high performance chromatography with UV and MS detector

(30) SFC: supercritical fluid chromatography with UV detector

(31) Identification of Synthesis Intermediates and Synthesis Final Products by Means of LC-MS:

(32) LC-MS method A:

(33) Column: Chromolith SpeedROD RP-18e 50-4.6 mm, flow rate: 2.4 ml/min., wavelength: 220 nm, eluent A: water+0.05% by vol. of formic acid, eluent B: acetonitrile+0.4% by vol. of formic acid, gradient: 4% by vol.-100% by vol. of eluent B in 2.8 min, then 100% of eluent B for a period of 0.5 min.

(34) LC-MS method B:

(35) Column: Chromolith SpeedROD RP-18e 50-4.6 mm, flow rate: 2.4 ml/min., wavelength: 220 nm, eluent A: water+0.1% by vol. of trifluoroacetic acid, eluent B: acetonitrile+0.1% by vol. of trifluoroacetic acid, gradient: 4% by vol.-100% by vol. of eluent B in 2.8 min, then 100% by vol. of eluent B for a period of 0.5 min.

(36) Separation of Stereoisomeric Mixtures by Means of HPLC and SFC:

(37) HPLC: firstly, a column screening is carried out for each stereoisomeric mixture, with the following columns: Chiralpak AD-H, Chiralpak AS-H, Chiralpak IA, Chiralpak IB, Chiralpak IC, Chiralcel OD-H, Chiralcel OJ-H, Lux Cellulose-2, Lux-Amylose-2, all columns: 250-4.6 mm.

(38) The most suitable column is used for the further measurements (for example determination of the enantiomeric ratio). Flow rate: 0.8 ml/min, wavelength: variable, is adapted corresponding to the extinction maximum and the eluents used. Eluent: the following solvents or solvent mixtures are used for the eluents: n-heptane, n-hexane, ethanol, methanol, 2-propanol, acetonitrile, ethyl acetate, dichloromethane; the following can be used as eluent additive: 0.01-0.5% by vol. of formic acid, 0.01-0.5% by vol. of diethylamine; gradients or isocratic measurement conditions are used as required.

(39) SFC: firstly, a column screening is carried out for each stereoisomeric mixture, with the following columns: Chiralpak AD-H, Chiralpak AS-H, Chiralpak IA, Chiralpak IB, Chiralpak IC, Chiralcel OD-H, Chiralcel OJ-H, Lux Cellulose-2, Lux-Amylose-2, all columns: 250-4.6 mm. The most suitable column is used for the further measurements (for example determination of the enantiomeric ratio). Flow rate: 5 ml/min, wavelength: variable, is adapted corresponding to the extinction maximum and the eluents used. Eluent: liquid carbon dioxide (>70 bar), co-eluent: the following solvents or solvent mixtures are used for the co-eluents: ethanol, methanol, isopropanol, acetonitrile, ethyl acetate, dichloromethane. The following can be used as eluent additive: 0.01-0.5% by vol. of formic acid, 0.01-0.5% by vol. of diethylamine. Gradients or isocratic measurement conditions are used as required.

(40) Biological Testing

(41) A) DNA-PK Assay (Biochemical)

(42) The kinase assay was carried out in streptavidin-coated 348-well microtitre flashplates. To this end, 1.5 g of DNA-PK/protein complex and 100 ng of biotinylated substrate, such as, for example, PESQEAFADLWKK-biotin-NH2 (biotin-DNA-PK peptide), were incubated for 90 min at room temperature in a total volume of 36.5 l (34.25 mM HEPES/KOH; 7.85 mM Tris HCl; 68.5 mM KCl; 5 M ATP; 6.85 mM MgCl.sub.2; 0.5 mM EDTA; 0.14 mM EGTA; 0.69 mM DTT; pH 7.4) with 500 ng of DNA from calf thymus, 0.1 Ci of 33P-ATP and 1.8% of DMSO per well with and without the test compound. The reaction was stopped using 50 l/well of 200 mM EDTA. After incubation for a further 30 min at room temperature, the liquid was removed. Each well was washed three times with 100 l of 0.9% saline solution. A nonspecific reaction (blank value) was determined using 10 M of an innate kinase inhibitor. The radioactivity measurement was carried out using a TopCount. IC.sub.50 values were calculated in RS1.

(43) Literature: Kashishian et al. (2003) Molecular Cancer Therapeutics 1257.

(44) B) DNA-PK Phosphorylation at Serine 2056 (Cellular)

(45) HCT116 cells were cultivated at 37 C. and 10% CO2 in MEM alpha medium with 10% of foetal calf serum and 2 mM glutamine. The cells were detached from the base of the culture vessels with the aid of trypsin/EDTA, centrifuged off in centrifuge tubes, taken up in fresh medium, and the cell density was determined. 100,000 cells were shown in 1 ml of culture medium per cavity of a 24-well cell culture plate and cultivated overnight. Next day, 10 M bleomycin (DNA intercalator and inductor of DNA double-strand breaks) and test substances in fresh culture medium were added to the cells, and these were cultivated for a further six hours. Cell lysis was subsequently carried out, and the cell lysates were added to a blocked 96-well ELISA plate coated with DNA-PK-specific antibodies (Sigma-Aldrich WH0005591M2: total DNA-PK; Abcam ab18192 or Epitomics EM09912: phospho-serine 2056 DNA-PK) and incubated at 4 C. overnight. The 96-well ELISA plates were subsequently treated with a detection antibody (Abcam ab79444: total DNA-PK) and a streptavidin-HRP conjugate. The development of the enzymatic reaction was carried out with the aid of a chemiluminescent reagent, the chemiluminescence was measured with the aid of a Mithras LB940. The signals with the phospho-DNA-PK-specific antibody were standardised to the signal with the antibody against the total protein DNA-PKc. The determination of IC50 values or of percentage values was carried out by referencing to the signal level of the bleomycin-treated vehicle control group (100% of the control). The DMSO control was used as blank.

(46) C) Kv11.1 (hERG) ION Channel Activity (Patch Clamp Assay)

(47) Method for the detection and characterisation of test substances which interfere with the Kv11.1 (hERG) channel: Kv11.1 (hERG, human ether a-go-go related gene) is a potassium channel which plays a central role for repolarisation of the cells in the ventricular cardiomyocytes.

(48) The patch-clamp measurement was carried out at room temperature in whole-cell configuration on human embryonic kidney cells (HEK293) which have been transfected in a stable manner with the hERG gene.

(49) The whole-cell configurations were carried out using an automated patch clamp device (Patchliner, Nanion Technologies, Munich). This is a glass chip-based system with which automated whole-cell measurements on up to 8 cells simultaneously are possible. The glass chip has a hole of defined size to which the cell is transferred into the Gigaseal by application of a reduced pressure and brought into the whole-cell configuration. Buffer, cell suspension and test substances were added to microchannels of the chip using a Teflon-coated pipette.

(50) The cells were clamped to a holding potential of 80 mV. For measurement of substance-promoted inhibition of the Kv11.1 channel, the following voltage protocol was applied at 10-second intervals: 51 ms/80 mV, 500 ms/+40 mV, 500 ms/40 mV, 200 ms/80 mV. The leakage current is subtracted by means of the P4 method. The cells were resuspended in extracellular buffer (EC) and applied to the chip. After the cell had been collected, the seal was improved by addition of a seal enhancer buffer. As soon as the whole-cell configuration had been reached, the seal enhancer buffer was washed out and replaced by extracellular buffer. The measurement started in EC for 1.5 min. DMSO (vehicle control, 0.1% of DMSO) was then applied, and the control current was recorded for 3 min. The test substance was subsequently added twice in the same concentration, and the potassium current was measured for 3.5 min in each case.

(51) If the measurement result of a test substance at an initial concentration of 10 M was smaller than ()50% effect (threshold value) (for example ()60% effect), the test substance was, in order to determine a dose/action relationship, added cumulatively in increasing concentration, where each concentration was measured for 5 min.

(52) The reference substance used was the Kv11.1 (hERG) ion channel blocker quinidine. The effects of test substances and quinidine were standardised to the associated vehicle control. The effect on the Kv11.1 (hERG) channel activity was assessed from the potassium current at 40 mV. For the calculation, the current was evaluated for the respective final trace. A test-substance-induced inhibition of the Kv11.1 (hERG) channel was standardised to the vehicle control (0.1% of DMSO).

(53) During the measurement, an aliquot of the test substance was taken for concentration determination. The sample was measured immediately by HPLC, and the final concentration was determined from a calibration curve.

(54) If the measurement result of a test substance at an initial concentration of 10 M is greater than or equal to ()50% effect (threshold value) (for example ()30% effect, i.e. 30% inhibition at 10 M), the K.sub.i is calculated in accordance with the following formula: K.sub.i=1.0E-5(100+% effect)/(% effect), [M].

(55) The measurement result of ()30% effect at a test substance concentration of 10 M gives a K.sub.i of 23 M.

(56) D) Kv11.1 Ion Channel Binding Assay

(57) Kv11.1 (hERG=human ether a go-go related enzyme) is a cardiac K.sup.+ channel which should if possible not interact with the test substances. This interaction is determined quantitatively with the aid of the Predictor hERG Fluorescence Polarizations (FP) Assays from Life Technologies. In the case of this assay principle, cardiomyocyte cell membranes having a certain proportion of Kv11.1 channels are isolated. A dye-labelled Kv11.1 binding partner gives a high fluorescence polarisation signal by interaction with the Kv11.1. In the case of displacement of the dye, a reduction in the fluorescence polarisation signal occurs.

(58) The assay is carried out automatically as follows: 15 nl of the test substances (highest concentration: 10 mM, 10 concentrations: dilution factors 1:3.16, DMSO) are transferred into an empty microtitre plates having 384 wells by means of an acoustic pipetter. 3 l of the isolated membranes are subsequently added. Membranes and test substances are incubated at 22 C. for 15 min (+/5 min). In the next step, the dye-labelled binding partner is added, followed by incubation at 22 C. After incubation for two hours, the measurement of the fluorescence polarisation is carried out on an Envision multimode Reader. Measured raw data are standardised with the aid of Genedata Assay Analyzer. The IC50 and % effect values are calculated in Genedata Condoseo.

(59) Chemical Synthesis

(60) Above and below, all temperatures are indicated in C.

(61) The stereochemical configuration assignments of enantiomeric Examples 27, 72, 82, 83, 135, 136, 185, 234, 251, 455 and 456 were confirmed by X-ray structural analyses. For Examples 234 and 251, the identification was carried out by crystallisation and X-ray structural analysis of a precursor.

(62) The other compounds denoted as chiral in the tables (asterisk on the asymmetrical C atom) were obtained by chromatography on a chiral solid phase. The enantiomer eluted first under the respective conditions was given the name Ena1, the enantiomer eluted second was given the name Ena2.

Examples 1 and 2

(3,5-Difluoropyridin-4-yl)-[4-fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]methanol (1) (4-Chloro-5-fluoropyridin-3-yl)-[4-fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]methanol (2)

(63) ##STR00012##

(64) (3-Bromo-4-fluorophenyl)acetonitrile (4.00 g, 18.32 mmol), bis(pinacolato)diboron (5.22 g, 20.15 mmol), potassium acetate (55.86 mmol) and bis(triphenylphosphine)palladium(II) chloride (15.2% of Pd) (393.53 mg, 0.55 mmol) were dissolved in oxygen-free 1,4-dioxane (40 ml, max. 0.005% of water) under argon. The reaction mixture was subsequently heated at a temperature of 130 C. for 90 min. When the reaction conversion was complete, the mixture was filtered through kieselguhr. The filtrate was diluted with dichloromethane (200 ml) and water (50 ml) and extracted. The organic phase was dried over sodium sulfate, subsequently filtered and evaporated to dryness in vacuo, giving [4-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetonitrile as oil (7.59 g, purity 81%, MS: 262.2 [M+H.sup.+), which was reacted further without further work-up.

(65) ##STR00013##

(66) 4-Fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetonitrile (7.60 g, 23.53 mmol), 1,4-dioxane (85.6 ml, max. 0.005% of water), 4-chloro-7-morpholin-4-ylquinazoline (5.00 g, 20.02 mmol), bis(tricyclohexylphosphine)palladium(II) dichloride (597.24 mg, 0.80 mmol) and sodium carbonate solution (2.0 M, 30 ml, 60.07 mmol) were initially introduced in a three-necked flask. The suspension obtained was heated at a temperature of 140 C. under a nitrogen atmosphere with stirring for a period of 2.5 h. When the reaction was complete, the mixture was cooled to room temperature and filtered through kieselguhr. The filtrate was diluted with ethyl acetate (250 ml) and water (100 ml) and extracted. The aqueous phase was rinsed twice with ethyl acetate (75 ml in each case). The combined organic phases were dried over sodium sulfate, subsequently filtered and evaporated to dryness in vacuo. For further work-up, the residue was suspended in methyl tert-butyl ether, filtered off and rinsed twice with further methyl tert-butyl ether (30 ml in each case). The filter cake was dried overnight in vacuo, giving [4-fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]acetonitrile (4.91 g, 13.49 mmol, MS: 349.1 [M+H.sup.+], 67% yield) as yellow solid.

(67) ##STR00014##

(68) [4-Fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]acetonitrile (400 mg, 1.12 mmol), 4-chloro-3,5-difluoropyridine (189.9 mg, 1.23 mmol) were dissolved in oxygen-free, degassed tetrahydrofuran (8 ml, max. 0.0075% of water) under a dry argon atmosphere. Potassium tert-butoxide (263.9 mg, 2.35 mmol) was subsequently added to the reaction mixture, during which a dark-red solution formed, which was stirred at room temperature for a further 30 min. When the reaction was complete, the mixture was diluted with saturated ammonium chloride solution (20 ml) and water (50 ml). The aqueous phase was subsequently extracted twice with dichloromethane (60 ml in each case). The organic phase was dried over sodium sulfate, filtered off and evaporated to dryness in vacuo in a rotary evaporator. The residue was purified by flash column chromatography (gradient: dichloromethane/0-4% by vol. of ethanol), giving a mixture (420 mg, about 5:3) of the oils (3,5-difluoropyridin-4-yl)-[4-fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]acetonitrile (263 mg, 0.57 mmol, MS: 462.1 [M+H.sup.+], 50% yield) and (4-chloro-5-fluoropyridin-3-yl)-[4-fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]acetonitrile (157 mg, 0.33 mmol, MS: 478.1/480.1 [M+H.sup.+], 29% yield).

(69) ##STR00015##

(70) The mixture (420 mg, about 5:3) of (3,5-difluoropyridin-4-yl)-[4-fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]acetonitrile and (4-chloro-5-fluoropyridin-3-yl)-[4-fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]acetonitrile was dissolved in acetonitrile (12.7 ml). Potassium tert-butoxide (80.90 mg, 0.72 mmol) was added to the reaction solution with stirring, during which a dark-red solution formed. After stirring for 15 min, the mixture was cooled to 0 C., and 30% hydrogen peroxide solution (276 l, 2.70 mmol) was subsequently added dropwise. The cooling bath was removed after stirring for 5 min at 0. The reaction solution was stirred at room temperature for a further 1 h. When the reaction conversion was complete, 10% sodium thiosulfate solution (5 ml) was added, and the mixture was diluted with water (25 ml). The aqueous solution was extracted twice with dichloromethane (50 ml in each case). The combined organic phases were dried over sodium sulfate, filtered off and evaporated to dryness in vacuo. The residue was purified by flash column chromatography (gradient: dichloromethane/0-4% by vol. of ethanol), giving a mixture (310 mg, about 3:1) of the oils (3,5-difluoropyridin-4-yl)-[4-fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]methanone (233 mg, 0.50 mmol, MS: 451.1 [M+H.sup.+]) and (4-chloro-5-fluoropyridin-3-yl)-[4-fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]methanone (77 mg, 0.16 mmol, MS: 467.1/469.1 [M+H.sup.+]).

(71) ##STR00016##

(72) The mixture (310 mg, about 3:1) of (3,5-difluoropyridin-4-yl)-[4-fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]methanone and (4-chloro-5-fluoropyridin-3-yl)-[4-fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]methanone was dissolved in methanol (15 ml). Sodium borohydride (30.4 mg, 0.80 mmol) was subsequently added (evolution of gas). The reaction solution was stirred at room temperature for 45 min. When the reaction was complete, the mixture was diluted with saturated ammonium chloride solution (5 ml) and water (15 ml). The aqueous phase was subsequently extracted three times with dichloromethane (20 ml in each case). The combined organic phases were dried over sodium sulfate, filtered off and evaporated to dryness in vacuo in a rotary evaporator. The residue was dissolved in dimethyl sulfoxide (4.8 ml) and purified by chromatography by means of preparative HPLC (gradient: water/1-50% by vol. of acetonitrile over 21 min, flow rate 50 ml/min). The product fractions were combined, diluted with saturated sodium hydrogencarbonate solution (5 ml in each case) and extracted twice with dichloromethane (40 ml in each case). The organic phases were evaporated in vacuo, the residues were subsequently taken up in 1,4-dioxane (5 ml) and water (30 ml) and freeze-dried, giving pure (3,5-difluoropyridin-4-yl)-[4-fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]methanol (EXAMPLE 1, 42.50 mg, 0.09 mmol, MS: 453.1 [M+H.sup.+]) and (4-chloro-5-fluoropyridin-3-yl)-[4-fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]methanol (EXAMPLE 2, 28.40 mg, 0.06 mmol, MS: 469.1/471.1 [M+H.sup.+]) as solids.

Example 37

(3-Chloropyrazin-2-yl)-[4-fluoro-3-(6-morpholin-4-ylthieno[3,2-d}pyrimidin-4-yl)phenyl]-methanol (37)

(73) ##STR00017##

(74) Sodium hydride (60% suspension in paraffin oil, 1.41 g, 35.0 mmol) was suspended in dry tetrahydrofuran (25 ml) under argon in a glass vessel. 4-Methoxyphenylmethanol (4.21 g, 30.0 mmol), dissolved in dry tetrahydrofuran (5 ml), was subsequently slowly added dropwise with stirring, and the mixture was stirred at room temperature for 1 h. A suspension of 4-chlorothieno[3,2-d}pyrimidine (4.00 g, 23.4 mmol) in dry tetrahydrofuran (20 ml) was then added slowly, and the mixture was stirred for a further hour. When the reaction conversion was complete, methanol (15 ml) was carefully added, the mixture was subsequently evaporated in vacuo and diluted with a mixture of water (100 ml) and ethyl acetate (150 ml). The aqueous phase was extracted three times with ethyl acetate (100 ml in each case), dried over sodium sulfate, filtered off with suction, and the filtrate was evaporated in vacuo. The solvent-free residue was taken up in ethanol (40 ml) and carefully stirred at about 5 C. for 16 h. The crystals which precipitated out overnight were filtered off with suction, rinsed with a little cold ethanol and dried at room temperature, giving 4-(4-methoxybenzyloxy)thieno[3,2-d]pyrimidine (4.15 g, 15.24 mmol, MS: 273.0 [M+H.sup.+]), 65% yield) as crystalline solid.

(75) ##STR00018##

(76) 4-(4-Methoxybenzyloxy)thieno[3,2-d}pyrimidine (2.60 g, 9.55 mmol) was dissolved in dry tetrahydrofuran (35 ml) and cooled to ()55 C. A freshly prepared lithium diisopropylamide solution (21 mmol, prepared from diisopropylamine [2.13 g, 21 mmol] and n-BuLi [15% solution from n-hexane, 13.13 ml, 21 mmol in dry tetrahydrofuran [35 ml] at []10 C.) was added dropwise at ()55 C. over 10 min. The suspension obtained was stirred further. 1,2-dibromoethane (10.76 g, 6.0 mmol) was subsequently added. After a further 10 min, the mixture was warmed to ()20 C. and stirred for 1 h. With the reaction complete, the reaction solution was added to a 50% aqueous sodium hydrogencarbonate/sodium thiosulfate solution (volume ratio 1:1, 120 ml). The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, subsequently dried over sodium sulfate, filtered and evaporated to dryness in a rotary evaporator. The residue was purified by means of flash column chromatography (gradient cyclohexane/0-18% by vol. of ethyl acetate, CombiFlash Rf 200, 80 g silica column, flow rate=50 ml/min., =220 nm), giving 6-bromo-4-(4-methoxybenzyloxy)thieno[3,2-d}pyrimidine (1.39 g, 3.95 mmol, MS: 351.0/353.0 [M+H.sup.+]), 41% yield) as solid.

(77) ##STR00019##

(78) 6-Bromo-4-(4-methoxybenzyloxy)thieno[3,2-d}pyrimidine (1.38 g, 3.93 mmol), morpholine (1.03 g, 11.79 mmol), sodium tert-butoxide (1.13 g, 11.79 mmol), (S)-()-2,2-bis(diphenylphosphino)-1,1-binaphtyl (S-BINAP, 122.3 mg, 0.196 mmol) and tris(dibenzylideneacetone)dipalladium (179.9 mg, 0.196 mmol) was dissolved in toluene (20 ml) under nitrogen in a microwave vessel. The reaction solution was heated at 95 C. for 4 h. The mixture was subsequently diluted with water (60 ml) and dichloromethane (60 ml). The aqueous phase was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and evaporated in a rotary evaporator. The residue was purified by means of flash chromatography (gradient dichloromethane/5-25% by vol. of [dichloromethane/ethanol 9:1], CombiFlash Rf 200, 80 g silica column, =220 nm). The suitable product fractions were combined, and the solvents were removed in a rotary evaporator, giving 4-(4-methoxybenzyloxy)-6-morpholin-4-ylthieno[3,2-d}pyrimidine (756.0 mg, 2.12 mmol, MS: 358.2 [M+H.sup.+]) 54% yield) as solid.

(79) ##STR00020##

(80) 4-(4-Methoxybenzyloxy)-6-morpholin-4-ylthieno[3,2-d}pyrimidine (923 mg, 2.58 mmol) was dissolved in tetrahydrofuran (5 ml) and methanol (5 ml). Pd/C (5%, 1.9 g) was added in portions (at the beginning of the reaction, after a further 7 h and 24 h), and the mixture was hydrogenated at a maximum hydrogen pressure of 5 bar (H.sub.2, purity 3.0, 57.9 g) for 36 h. The solution obtained was filtered through kieselguhr and evaporated in a rotary evaporator. The residue was purified by means of flash column chromatography (gradient: dichloromethane/10-20% by vol. of [methanol/ammonia 10:1], CombiFlash Rf 200, 24 g silica column, =220 nm). The suitable product fractions were combined, and the solvents were removed in a rotary evaporator, giving 6-morpholin-4-yl-3H-thieno[3,2-d}pyrimidin-4-one (361.0 mg, 1.521 mmol, MS: 238.0 [M+H.sup.+], 59% yield) as solid.

(81) ##STR00021##

(82) 6-Morpholin-4-yl-3H-thieno[3,2-d}pyrimidin-4-one (206 mg, 0.87 mmol) was suspended in phosphoryl chloride (1.67 g, 10.89 mmol). N-Ethyldiisopropylamine (56.1 mg, 0.43 mmol) was subsequently added to the suspension. The reaction mixture was stirred overnight at room temperature. For work-up, a mixture of saturated sodium hydrogencarbonate solution (30 ml) and dichloromethane (20 ml) was added. The resultant solution was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate, filtered and evaporated to dryness in vacuo, giving 4-chloro-6-morpholin-4-ylthieno[3,2-d}-pyrimidine (127 mg, 0.497 mmol, MS: 256.0/258.0 [M+H.sup.+], 57% yield) as solid.

(83) ##STR00022##

(84) Starting from 4-chloro-6-morpholin-4-ylthieno[3,2-d}pyrimidine, (3-chloropyrazin-2-yl)-[4-fluoro-3-(6-morpholin-4-ylthieno[3,2-d}pyrimidin-4-yl)phenyl]methanol (EXAMPLE 37) was prepared analogously to the synthesis sequence described for Examples 1 and 2.

(85) Compounds which were prepared in accordance with Examples 1, 2 and 37 can be found in Table 1 below.

(86) TABLE-US-00001 TABLE 1 Compounds of the formula (I) IC.sub.50 IC.sub.50 K.sub.i DNA- pDNA- [Kv1.11 Example Structural formula Name PK PK hERG] 1 (3,5-Difluoro-pyridin-4- yl)-[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol B B B MS: 453.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 8.50 (s, 2H), 7.65-7.60 (m, 2H), 7.55-7.48 (m, 2H), 7.45-7.40 (m, 1 H), 7.20 (d, J = 2.1, 1H), 6.62 d, J = 4.6, 1H), 6.23 (d, J = 4.6, 1H), 3.80-3.75 (m, (4H), 3.47-3.42 (m, 4H) 2 (4-Chloro-5-fluoro- pyridin-3-yl)-[4-fluoro-3- (7-morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol B A C MS: 469.1/471.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), (Cl isotopy, rel. peak 8.70 (s, 1H), 8.66 (s, 1H), 7.64-7.59 (m, 2H), 7.55- intensity ratio [%] 100:37) 7.48 (m, 2H), 7.44-7.39 (m, 1H), 7.20 (d, J = 2.2, 1H), 6.56 (d, J = 4.4, 1H), 6.12 (d, J = 4.5, 1H), 3.81- 3.74 (m, 4H), 3.47-3.40 (m, 4H) 3 [2-Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (4-methoxy-pyridazin-3- yl)methanol B B A MS: 504.1/506.1 (M + Na.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.13 (s, 1H), (Cl isotopy, rel. peak 8.96 (d, J = 6.0, 1H), 8.04 - 8.01 (m, 1H), 7.65 - intensity ratio [%] 100:35) 7.60 (m, 2H), 7.56 (dd, J = 9.4, 2.5, 1H), 7.32 (d, J = 6.0, 1H), 7.22 (d, J = 2.5, 1H), 6.46 (d, J = 6.2, 1H), 6.39 (d, J = 6.3, 1H), 3.96 (s, 3H), 3.81 - 3.75 (m, 4H), 3.50 - 3.43 (m, 4H) 4 [2-Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (5-methoxy-pyridazin-3- yl)methanol A A A MS: 482.1/484.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.07 (s, 1H), (Cl isotopy, rel. peak 8.88 (d, J = 4.7, 1H), 7.71 (d, J = 9.5, 1H), 7.59 (dd, intensity ratio [%] 100:34) J = 4.7, 0.9, 1H), 7.54 (d, J = 7.6, 1H), 7.52-7.50 (m, 2H), 7.21-7.17 (m, 1H), 6.46 (d, J = 5.1, 1H), 6.15 (d, J = 5.2, 1H), 4.01 (s, 3H), 3.81-3.74 (m, 4H), 3.48-3.41 (m, 4H) 5 3-{[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- hydroxymethyl}-1H- pyrazin-2-one D D B MS: 434.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 7.69-7.59 (m, 2H), 7.56-7.50 (m, 2H), 7.39- 7.28 (m, 3H), 7.20 (d, J = 2.1, 1H), 6.00 (s, 1H), 5.87-5.75 (m, 1H), 3.81-3.74 (m, 4H), 3.44 (t, J = 5.0, 4H) 6 [2-Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (6-chloro-5-methoxy- pyridazin-3-yl)methanol A A C MS: 516.1/518.1/520.1 1H NMR (500 MHz, DMSO-d6) ppm = 9.07 (s, 1H), (M + H.sup.+) (Cl.sub.2 isotopy, rel. 7.75 (d, J = 1.0, 1H), 7.72 (d, J = 9.5, 1H), 7.56 (d, peak intensity ratio [%] J = 7.6, 1H), 7.51 (dd, J = 9.5, 2.5, 1H), 7.47 (dd, 100:71:14) J = 9.4, 2.9, 1H), 7.19 (d, J = 2.4, 1H), 6.59 (d, J = 5.0, 1H), 6.13-6.10 (m, 1H), 3.98 (s, 3H), 3.80-3.74 (m, 4H), 3.48-3.41 (m, 4H) 7 (3-Chloro-6-methoxy- pyridazin-4-yl)-[4-fluoro- 3-(7-morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol B A B MS: 482.1/484.1 (M + H + ) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), (Cl isotopy, rel. peak 7.62-7.57 (m, 2H), 7.55-7.47 (m, 3H), 7.43- intensity ratio [%] 100:39) 7.39 (m, 1H), 7.20 (d, J = 2.4, 1H), 6.58 (d, J = 4.5, 1H), 5.88 (d, J = 4.4, 1H), 4.04(s, 3H), 3.80-3.75 (m, 4H), 3.46-3.42 (m, 4H) 8 0 [2-Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (6-chloro-4-methoxy- pyridazin-3-yl)methanol C B C MS: 516.1/518.1/520.1 1H NMR (500 MHz, DMSO-d6) ppm = 9.13 (s, 1H), (M + H.sup.+) (Cl.sub.2 isotopy, rel. 8.01-7.99 (m, 1H), 7.65-7.59 (m, 3H), 7.56 (dd, peak intensity ratio [%] J = 9.5, 2.5, 1H), 7.22 (d, J = 2.5, 1H), 6.52 (d, J = 6.2, 100:72:16) 1H), 6.39 (d, J = 6.2, 1H), 4.02 (s, 3H), 3.80-3.76 (m, 4H), 3.48-3.44 (m, 4H) 9 (6-Chloro-5-methoxy- pyridazin-3-yl)-[4-fluoro- 3-(7-morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol B A D MS: 482.1/484.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), (Cl isotopy, rel. peak 7.88 (d, J = 1.0, 1H), 7.63-7.58 (m, 2H), 7.55- intensity ratio [%] 100:38) 7.47 (m, 2H), 7.42-7.35 (m, 1H), 7.20 (d, J = 2.3, 1H), 6.46 (d, J = 4.3, 1H), 5.85-5.82 (m, 1H), 4.00 (s, 3H), 3.81-3.74 (m, 4H), 3.48-3.41 (m, 4H) 10 (6-Chloro-4-methoxy- pyridazin-3-yl)-[4-fluoro- 3-(7-morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol B A A MS: 482.1/484.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), (Cl isotopy, rel. peak 7.64-7.60 (m, 2H), 7.53-7.51 (m, 3H), 7.40- intensity ratio [%] 100:38) 7.35 (m, 1H), 7.21-7.19 (m, 1H), 6.29 (d, J = 5.3, 1H), 6.18 (d, J = 4.3, 1H), 3.93 (s, 3H), 3.80-3.75 (m, 4H), 3.46-3.42 (m, 4H) 11 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (5-methoxy-pyridazin-3- yl)methanol (Ena 1) B A C MS: 448.2 (M + H.sup.+); R.sub.t see racemate 6.1 min (SFC, Chiracel OJ- H, CO.sub.2/15% by vol. of methanol, 0.5% by vol. of diethylamine) 12 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (5-methoxy-pyridazin-3- yl)methanol (Ena 2) A B B MS: 448.2 (M + H.sup.+); R.sub.t see racemate 8.72 min (SFC, Chiracel OJ-H, CO.sub.2/15% by vol. of methanol, 0.5% by vol. of diethylamine) 13 (3-tert-Butoxy-pyrazin- 2-yl)-[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol D D C MS: 490.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.14 (d, J = 2.7, 1H), 8.08 (d, J = 2.7, 1H), 7.63- 7.56 (m, 2H), 7.54-7.47 (m, 2H), 7.40-7.35 (m, 1H), 7.21-7.18 (m, 1H), 5.97 (d, J = 6.0, 1H), 5.91 (d, J = 6.1, 1H), 3.81-3.75 (m, 4H), 3.47-3.41 (m, 4H), 1.47 (s, 9H) 14 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (3-pyrrolidin-1-yl- pyrazin-2-yl)methanol B B A MS: 487.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm =9.09 (s, 1H), 7.99 (d, J = 2.4, 1H), 7.80 (d, J = 2.5, 1H), 7.58- 7.52 (m, 4H), 7.38-7.32 (m, 1H), 7.21-7.17 (m, 1H), 6.18-6.13 (m, 1H), 6.09-6.01 (m, 1H), 3.78 (t, J = 4.9, 4H), 3.68-3.56 (m, 4H), 3.44 (t, J = 4.9, 4H), 1.96-1.81 (m, 4H) 15 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (3-methoxy-pyrazin-2- yl)methanol (Ena 2) A A B MS: 448.2 (M + H.sup.+); Rt see racemate 19.73 min, (HPLC, Chiracel OJ-H, methanol) 16 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (3-methoxy-pyrazin-2- yl)methanol (Ena 1) C B A MS: 448.2 (M + H.sup.+); R.sub.t see racemate 7.55 min, (HPLC, Chiracel OJ-H, methanol) 17 (3,5-Dichloro-pyridin-4- yl)-[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol B B C MS: 485.1/487.1/489.1 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), (M + H.sup.+) (Cl.sub.2 isotopy, rel. 8.62 (s, 2H), 7.58-7.48 (m, 4H), 7.43-7.37 (m, peak intensity ratio [%] 1H), 7.19 (d, J = 2.2, 1H), 6.70-6.65 (m, 1H), 6.52 100:64:11) (d, J = 4.7, 1H), 3.81-3.74 (m, 4H), 3.48-3.40 (m, 4H) 18 0 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (4-methoxy-pyridazin-3- yl)methanol A B B MS: 448.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11-9.08 (m, 1H), 8.99-8.95 (m, 1H), 7.65-7.59 (m, 2H), 7.55-7.50 (m, 2H), 7.40-7.34 (m, 1H), 7.27 (d, J = 5.9, 1H), 7.22-7.18 (m, 1H), 6.24-6.18 (m, 2H), 3.88 (s, 3H), 3.81-3.74 (m, 4H), 3.48-3.40 (m, 4H) 19 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (5-methoxy-pyridazin-3- yl)methanol A A A MS: 448.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11-9.08 (m, 1H), 8.94-8.90 (m, 1H), 7.80-7.77 (m, 1H), 7.59-7.55 (m, 2H), 7.51 (qd, J = 9.4, 2.5, 2H), 7.41- 7.35 (m, 1H), 7.20 (d, J = 2.3, 1H), 6.34-6.31 (m, 1H), 5.87 (d, J = 4.2, 1H), 4.01 (s, 3H), 3.8 -3.74 (m, 4H), 3.48-3.40 (m, 4H) 20 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- imidazo[1,2-b]pyridazin- 6-ylmethanol (Ena 2) C C A MS: 475.2 (M + H.sup.+); R.sub.t see racemate 15.12 min (HPLC, Chiralpak AD-H, n-heptane/2-propanol, 1:9 vol./vol.) 21 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- imidazo[1,2-b]pyridazin- 6-ylmethanol (Ena 1) A A A MS: 475.2 (M + H.sup.+); R.sub.t - see racemate 8.05 min (HPLC, Chiralpak AD-H, n-heptane/2-propanol, 1:9 vol./vol.) 22 (2-Chloro-5-methoxy- pyridin-3-yl)-[4-fluoro-3- (7-morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol A A D MS: 481.2/483.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), (Cl isotopy, rel. peak 8.28 (d, J = 2.6, 1H), 7.62-7.55 (m, 3H), 7.55- intensity ratio [%] 100:30) 7.49 (m, 2H), 7.41-7.32 (m, 1H), 7.21-7.18 (m, 1H), 6.16 (d, J = 6.1, 1H), 6.03 (d, J = 6.1, 1H), 3.85 (s, 3H), 3.80-3.75 (m, 4H), 3.47-3.42 (m, 4H) 23 (3-Chloro-pyrazin-2-yl)- [4-fluoro-3-(6- morpholin-4-yl-thieno- [3,2-d}pyrimidin-4-yl)- phenyl]methanol (Ena 1) C C A MS: 458.1/460.1 (M + H.sup.+) identical to enantiomer (24) (Cl isotopy, rel. peak intensity ratio [%] 100:41); R.sub.t 4.96 min (SFC, Chiracel OD-H, CO.sub.2/30% by vol. methanol) 24 (3-Chloro-pyrazin-2-yl)- [4-fluoro-3-(6- morpholin-4-yl-thieno- [3,2-d}pyrimidin-4-yl)- phenyl]methanol (Ena 2) A A B MS: 458.1/460.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 8.88 (s, 1H), (Cl isotopy, rel. peak 8.68 (d, J = 2.4, 1H), 8.47 (d, J = 2.4, 1H), 7.73 (dd, intensity ratio [%] 100:40); J = 7.0, 2.3, 1H), 7.66-7.61 (m, 1H), 7.39 (dd, R.sub.t 7.13 min (SFC, Chiracel J = 10.3, 8.6, 1H), 6.52 (s, 1H), 6.39 (d, J = 5.7, 1H), OD-H, CO.sub.2/30% by vol. 6.21 (d, J = 5.7, 1H), 3.78-3.71 (m, 4H), 3.44- methanol) 3.37 (m, 4H). 25 (6-Chloro-3-methoxy- pyrazin-2-yl)44-fluoro- 3-(7-morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol B A D MS: 482.1/484.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, 1H), (Cl isotopy, rel. peak 8.30 (s, 1H), 7.65-7.60 (m, 2H), 7.57-7.51 (m, intensity ratio [%] 100:36) 2H), 7.43-7.36 (m, 1H), 7.22-7.19 (m, 1H), 6.18 (s, 1H), 6.06-6.02 (m, 1H), 3.94 (s, 3H), 3.81- 3.75 (m, 4H), 3.47-3.43 (m, 4H) 26 (3-Chloro-6-methoxy- pyrazin-2-yl)44-fluoro- 3-(7-morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol A A A MS: 482.1/484.1 (M + H + ) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), (Cl isotopy, rel. peak 8.11 (s, 1H), 7.73-7.68 (m, 2H), 7.54-7.50 (m, intensity ratio [%] 100:35) 2H), 7.44-7.38(m, 1H), 7.21-7.19 (m, 1H), 6.31 (d, J = 5.7, 1H), 6.11 (d, J = 5.8, 1H , 3.89 (s, 3H), 3.80-3.75 (m, 4H), 3.47-3.41 (m, 4H) 27 (R)-(3-Chloro-pyrazin-2- yl)-[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol A A A MS: 452.1/454.1 (M + H.sup.+) see racemate (Cl isotopy, rel. peak intensity ratio [%] 100:40); R.sub.t 67.12 min, (HPLC, ChiralPak AD-H, ethanol) 28 0 (S)-(3-Chloro-pyrazin-2- yl)-[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol C C B MS: 452.1/454.1 (M + H.sup.+) see racemate (Cl isotopy, rel. peak intensity ratio [%] 100:40); R.sub.t 37.09 min, (HPLC, ChiralPak AD-H, ethanol) 29 [2-Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- pyridazin-3-ylmethanol (Ena 2) C D B MS: 452.1/454.0 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.14 (dd, (Cl isotopy, rel. peak J = 4.9, 1.7, 1H), 9.11 (s, 1H), 7.88 (d, J = 7.7, 1H), intensity ratio [%] 100:35); 7.80 (dd, J = 8.6, 1.7, 1H), 7.72-7.66 (m, 2H), 7.58 R.sub.t 5.61 mm (SFC, (dd, J = 9.4, 3.3, 1H), 7.53 (dd, J = 9.5, 2.5, 1H), 7.21 ChiralPak IA, CO.sub.2/40% (d, J = 2.4, 1H), 6.71 (d, J = 5.0, 1 H), 6.32 (d, J = 4.9, by vol. of 2-propanol, 1H), 3.80-3.75 (m, 4H), 3.47-3.43 (m, 4H) 0.5% by vol. of diethylamine) 30 [2-Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- pyridazin-3-ylmethanol (Ena 1) A A B MS: 474.1/476.1 (M + Na.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.14 (dd, (Cl isotopy, rel. peak J = 4.9, 1.7, 1H), 9.11 (s, 1H), 7.88 (d, J = 7.7, 1H), intensity ratio [%] 100:34); 7.80 (dd, J = 8.6, 1.7, 1H), 7.73-7.66 (m, 2H), 7.58 R.sub.t 2.87min (SFC, (dd, J = 9.4, 3.3, 1H), 7.53 (dd, J = 9.5, 2.5, 1H), 7.21 ChiralPak IA, CO.sub.2/40% (d, J = 2.4, 1H), 6.71 (d, J = 5.0, 1H), 6.32 (d, J = 4.9, by vol. of 2-propanol, 1H), 3.80-3.75 (m, 4H), 3.48-3.42 (m, 4H) 0.5% by vol. of diethylamine) 31 (3-Chloro-5-methoxy- pyridin-2-yl)-[4-fluoro-3- (7-morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol A A C MS: 481.1/482.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), (Cl isotopy, rel. peak 8.28 (d, J = 2.6, 1H), 7.62-7.55 (m, 3H), 7.55- intensity ratio [%] 100:30) 7.49 (m, 2H), 7.41-7.32 (m, 1H), 7.21-7.18 (m, 1H), 6.16 (d, J = 6.1, 1H), 6.03 (d, J = 6.1, 1H), 3.85 (s, 3H), 3.80-3.75 (m, 4H), 3.47-3.42 (m, 4H) 32 [4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- [3-(oxetan-3-yloxy)- pyrazin-2-yl]methanol C C B MS: 490.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.24 (d, J = 2.7, 1H), 8.09 (d, J = 2.8, 1H), 7.71- 7.64 (m, 2H), 7.54-7.51 (m, 2H), 7.42-7.36 (m, 1H), 7.22-7.19 (m, 1H), 6.15-6.11 (m, 2H), 5.63- 5.58 (m, 1H), 4.88-4.83 (m, 2H), 4.58-4.52 (m, 2H), 3.80-3.75 (m, 4H), 3.47-3.41 (m, 4H) 33 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- pyrazin-2-ylmethanol C D D MS: 418.1 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 8.89 (d, J = 1.5, 1H), 8.59-8.53 (m, 2H), 7.71- 7.65 (m, 2H), 7.57-7.50 (m, 2H), 7.44-7.37 (m, 1H), 7.21-7.19 (m, 1H), 5.94(s, 1H), 3.81-3.75 (m, 4H), 3.49-3.44 (m, 4H) 34 [2-Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- pyrazin-2-ylmethanol C C B MS: 452.1/454.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, 1H), (CI isotopy, rel. peak 8.86 (d, J = 1.3, 1H), 8.58-8.55 (m, 2H), 7.88 (d, intensity ratio [%] 100:36) J = 7.7, 1H), 7.66 (d, J = 9.5, 1H), 7.60-7.52 (m, 2H), 7.21 (d, J = 2.3, 1H), 6.62 (d, J = 4.9, 1H), 6.19 (d, J = 4.8, 1H), 3.80-3.75 (m, 4H), 3.49-3.42 (m, 4H) 35 (3,6-Dichloro-pyrazin-2- yl)-[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol A A C MS: 486.1/488.1/490.0 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), (M + H.sup.+) (Cl.sub.2 isotopy, rel. 8.63 (s, 1H), 7.68-7.64 (m, 2H), 7.55-7.51 (m, peak intensity ratio [%] 2H), 7.45-7.40 (m, 1H), 7.20 (d J = 2.1, 1H), 6.51 100:65:15) (d, J = 5.5, 1H), 6.18 (d, J = 5.5, 1H , 3.81-3.75 (m, 4H), 3.48-3.41 (m, 4H) 36 [2-Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- pyridazin-4-ylmethanol A A A MS: 452.1/454.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.27-9.25 (Cl isotopy, rel. peak (m, 1H), 9.19 (dd, J = 5.3, 1.2, 1H), 9.11 (s, 1H), intensity ratio [%] 100:33) 7.89 (d, J = 7.6, 1H), 7.72 (d, J = 9.5, 1H), 7.62- 7.56 (m, 2H), 7.53 (dd, J = 9.4, 2.5, 1H), 7.21 (d, J = 2.4, 1H), 6.72 (s, 1H), 6.13 (s, 1H), 3.81-3.75 (m, 4H), 3.48-3.43 (m, 4H) 37 (3-Chloro-pyrazin-2-yl)- [4-fluoro-3-(6- morpholin-4-ylthieno- [3,2-d}pyrimidin-4-yl)- phenyl]methanol A A C MS: 458.1/460.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 8.88 (s, 1H), (Cl isotopy, rel. peak 8.68 (d, J = 2.4, 1H), 8.47 (d, J = 2.4, 1H), 7.73 (dd, intensity ratio [%] 100:39) J = 7.0, 2.3, 1H), 7.66-7.61 (m, 1H), 7.43-7.35 (m, 1H), 6.52 (s, 1H), 6.39 (d, J = 5.7, 1H), 6.21 (d, J = 5.6, 1H), 3.77-3.71 (m, 4H), 3.44-3.37 (m, 4H) 38 0 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (3-methoxy-pyrazin-2- yl)methanol A A A MS: 448.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.19 (d, J = 2.7, 1H), 8.15 (d, J = 2.7, 1H), 7.64- 7.59 (m, 2H), 7.55-7.50 (m, 2H), 7.39-7.34 (m, 1H), 7.21-7.18 (m, 1H), 6.08 (d, J = 5.9, 1H), 6.04 (d, J = 5.9, 1H), 3.93 (s, 3H), 3.80-3.75 (m, 4H), 3.47-3.42 (m, 4H) 39 [2-Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- pyrazolo[1,5-a]- pyrimidin-5-ylmethanol B A B MS: 491.1/493.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, 1H), (Cl isotopy, rel. peak 9.08 (dd, J = 7.2, 0.9, 1H), 8.19 (d, J = 2.4, 1H), 7.87 intensity ratio [%] 100:38) (d, J = 7.7, 1H), 7.69 (d, J = 9.5, 1H), 7.58 (dd, J = 9.4, 3.2, 1H), 7.52 (dd, J = 9.5, 2.5, 1H), 7.21 (d, J = 2.5, 1H), 7.17 (d, J = 7.3, 1H), 6.71 (d, J = 5.0, 1H), 6.67 (dd, J = 2.3, 0.9, 1H), 6.11 (d, J = 4.8, 1H), 3.82- 3.74 (m, 4H), 3.49-3.41 (m, 4H) 40 [2-Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (4-methoxypyrido- [3,4-d}pyridazin-1-yl)- methanol C B C MS: 533.2/535.2 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.97 (s, 1H), (Cl isotopy, rel. peak 9.15 (s, 1H), 9.11 (d, J = 5.5, 1H), 8.10-8.02 (m, intensity ratio [%] 100:38) 2H), 7.73-7.62 (m, 2H), 7.57 (dd, J = 9.5, 2.5, 1H), 7.23 (d, J = 2.4, 1H), 6.95-6.87(m, 2H), 4.18 (s, 3H), 3.84-3.74 (m, 4H), 3.52-3.41 (m, 4H) 41 [2-Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (6-chloro-pyridazin-3- yl)methanol B A B MS: 486.0/488.1/490.0 1H NMR (400 MHz, DMSO-d6) ppm = 9.11 (s, 1H), (M + H.sup.+) (Cl.sub.2 isotopy, rel. 7.92-7.90 (m, 2H), 7.90-7.87 (m, 1H), 7.69 (d, peak intensity ratio [%] J = 9.5, 1H), 7.58 (dd, J = 9.4, 3.2, 1H), 7.53 (dd, 100:67:17) J = 9.5, 2.4, 1H), 7.20 (d, J = 2.3, 1H), 6.86 (d, J = 5.0, 1H), 6.32 (d, J = 4.5, 1H), 3.81-3.74 (m, 4H), 3.48- 3.43 (m, 4H) 42 (3-Chloro-pyridin-2-yl)- [4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol A A B MS: 451.1/452.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), (Cl isotopy, rel. peak 8.56 (dd, J = 4.6, 1.4, 1H), 7.92 (dd, J = 8.1, 1.4, 1H), intensity ratio [%] 100:35) 7.64-7.59 (m, 2H), 7.54-7.49 (m, 2H), 7.40- 7.34 (m, 2H), 7.22-7.17 (m, 1H), 6.21 (s, 1H), 6.18-6.09 (m, 1H), 3.81-3.73 (m, 4H), 3.48- 3.40 (m, 4H) 43 6-([2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)phenyl]- hydroxymethyl}- pyridazine-3-carboxylic acid methylamide B B A MS: 531.2/533.2 (M + Na.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.14 (q, (Cl isotopy, rel. peak J = 4.7, 1H), 9.11 (s, 1H), 8.19 (d, J = 8.7, 1H), 7.99 intensity ratio [%] 100:39) (d, J = 8.7, 1H), 7.87 (d, J = 7.7, 1H), 7.69 (d, J = 9.5, 1H), 7.58-7.51 (m, 2H), 7.22-7.19 (m, 1H), 6.84 (s, 1H), 6.42 (s, 1H), 3.80-3.76 (m, 4H), 3.47- 3.42 (m, 4H), 2.85 (d, J = 4.7, 3H) 44 6-{[2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)phenyl]- hydroxymethyl}-2- methyl-2H-pyridazin-3- one (Ena 2) C C B MS: 482.0/484.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, 1H), (Cl isotopy, rel. peak 7.93 (d, J = 7.7, 1H), 7.68 (d, J = 9.5, 1H), 7.61- intensity ratio [%] 100:35) 7.52 (m, 2H), 7.48 (d, J = 9.6, 1H), 7.21 (d, J = 2.4, R.sub.t 5.91 min, (SFC, 1H), 6.93 (d, J = 9.6, 1H), 6.60 (d, J = 4.8, 1H), 5.89 Chiralcel OJ-H,CO.sub.2/20% (d, J = 4.8, 1H), 3.80-3.75 (m, 4H), 3.59 (s, 3H), by vol. of methanol, 0.5% 3.48-3.43 (m, 4H) by vol. of diethylamine) 45 6-([2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)phenyl]- hydroxymethyl}-2- methyl-2H-pyridazin-3- one (Ena 1) A A B MS: 482.1/484.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, 1H), (Cl isotopy, rel. peak 7.93 (d, J = 7.7, 1H), 7.68 (d, J = 9.5, 1H), 7.60- intensity ratio [%] 100:35) ) 7.52 (m, 2H), 7.48 (d, J = 9.6, 1H), 7.21 (d, J = 2.4, R.sub.t 4.10 min, (SFC, 1H), 6.93 (d, J = 9.6, 1H), 6.60 (d, J = 4.9, 1H), 5.89 Chiralcel OJ-H, CO.sub.2/20% (d, J = 4.8, 1H), 3.81-3.75 (m, 4H), 3.59 (s, 3H), by vol. of methanol, 0.5% 3.48-3.42 (m, 4H) by vol. of diethylamine) 46 [2-Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (5-methylpyridazin-3- yl)methanol C C B MS: 488.1/490.2 (M + Na.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, 1H), (Cl isotopy, rel. peak 9.00 (d, J = 2.0, 1H), 7.87 (d, J = 7.7, 1H), 7.67 (d, intensity ratio [%] 100:32) J = 9.5, 1H), 7.63-7.61 (m, 1H), 7.58 (dd, J = 9.4, 3.3, 1H), 7.53 (dd, J = 9.5, 2.5, 1H), 7.21 (d, J = 2.4, 1H), 6.65 (d, J = 4.9, 1H), 6.28 (d, J = 4.9, 1H), 3.80- 3.75 (m, 4H), 3.48-3.42 (m, 4H), 2.32 (s, 3H) 47 [2-Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- pyridazin-3-ylmethanol B A A MS: 452.1/454.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.16-9.12 (Cl isotopy, rel. peak (m, 1H), 9.12-9.09 (m, 1H), 7.91-7.86 (m, 1H), intensity ratio [%] 100:39) 7.81-7.77 (m, 1H), 7.73-7.65 (m, 2H), 7.61- 7.56 (m, 1H), 7.55-7.51 (m, 1H), 7.23-7.19 (m, 1H), 6.72-6.69 (m, 1H), 6.34-6.30 (m, 1H), 3.81- 3.75 (m, 4H), 3.48-3.42 (m, 4H) 48 0 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- pyridazin-3-ylmethanol B B B MS: 436.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.14 (dd, J = 4.9, 1.6, 1H), 9.10 (s, 1H), 7.86 (dd, J = 8.5, 1.6, 1H), 7.81 (t, J = 8.1, 1H), 7.72 (dd, J = 8.5, 4.9, 1H), 7.58-7.51 (m, 2H), 7.46 (t, J = 10.1, 1H), 7.20(d, J = 2.3, 1H), 6.66 (d, J = 4.9, 1H), 6.26 (d, J = 4.9, 1H), 3.81-3.75 (m, 4H), 3.45 (t, J = 4.9, 4H) 49 (6-Chloro-pyridazin-3- yl)-[2,4-difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol A B A MS: 470.1/471.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), (Cl isotopy, rel. peak 7.98-7.91 (m, 2H), 7.82 (t, J = 8.1, 1H), 7.58-7.51 intensity ratio [%] 100:35) (m, 2H), 7.47(t, J = 10.1, 1H), 7.20 (d, J = 2.3, 1H), 6.78 (d, J = 4.9, 1H), 6.26 (d, J = 4.6, 1H), 3.82- 3.74 (m, 4H), 3.48-3.41 (m, 4H) 50 6-1[2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)phenyl]- hydroxymethyll- pyridazine-3-carboxylic acid dimethylamide C D A MS: 523.2/525.2 (M + H.sup.+) 1H NMR (500 MHz, chloroform-d) ppm = 9.15 (s, (Cl isotopy, rel. peak 1H), 7.85 (d, J = 8.7, 1H), 7.79 (d, J = 7.4, 1H), 7.65 intensity ratio [%] 100:35) (d, J = 8.7, 1H), 7.56 (dd, J = 9.3, 3.3, 1H), 7.36 (d, J = 9.0, 1H), 7.27 (d, J = 2.5, 1H), 7.22 (d, J = 2.5, 1H), 6.54 (s, 1H), 4.99 (s, 1H), 3.92-3.87 (m, 4H), 3.46-3.42 (m, 4H), 3.22 (s, 3H), 3.19 (s, 3H) 51 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- imidazo[1,2-b]pyridazin- 6-ylmethanol A A B MS: 475.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, 1H), 8.26 (s, 1H), 8.12 (d, J = 9.5, 1H), 7.92 (t, J = 8.1, 1H), 7.77 (s, 1H), 7.61-7.51 (m, 2H), 7.48 (t, J = 10.1, 1H), 7.35 (d, J = 9.5, 1H), 7.21 (d, J = 2.4, 1H), 6.75 (d, J = 4.9, 1H), 6.10 (d, J = 4.7, 1H), 3.78 (t, J = 4.9, 4H), 3.45 (t, J = 4.9, 4H) 52 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (5-methoxy-pyrazin-2- yl)methanol (Ena 1) B C A MS: 448.2 (M + H.sup.+); R.sub.t 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 16.15 min, (HPLC, 2 8.39-8.38 (m, 1H), 8.23 (d, J = 1.3, 1H), 7.66- Chiralcel OJ-H, methanol) 7.61 (m, 2H), 7.55-7.50 (m, 2H), 7.40-7.35 (m, 1H), 7.21-7.18 (m, 1H), 6.30 (d, J = 4.4, 1H), 5.88 (d, J = 4.4, 1H), 3.89 (s, 3H), 3.80-3.75 (m, 4H), 3.46-3.42 (m, 4H) 53 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (5-methoxy-pyrazin-2- yl)methanol (Ena 2) B C A MS: 448.2 (M + H.sup.+); R.sub.t 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 19.06 min, (HPLC, 2 8.39-8.38 (m, 1H), 8.23 (d, J = 1.3, 1H), 7.66- Chiralcel OJ-H, methanol) 7.61 (m, 2H), 7.55-7.50 (m, 2H), 7.40-7.35 (m, 1H), 7.21-7.18 (m, 1H), 6.30 (d, J = 4.4, 1H), 5.88 (d, J = 4.4, 1H), 3.89 (s, 3H), 3.80-3.75 (m, 4H), 3.46-3.42 (m, 4H) 54 S(3-Chloro-pyrazin-2-yl)- [4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol A A B MS: 452.1/453.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), (Cl isotopy, rel. peak 8.69 (d, J = 2.4, 1H), 8.46 (d, J = 2.4, 1H), 7.67- intensity ratio [%] 100:35) 7.63 (m, 2H), 7.54-7.52 (m, 2H), 7.43-7.37 (m, 1H), 7.20-7.19 (m, 1H), 6.39 (d, J = 5.7, 1H), 6.23 (d, J = 5.7, 1H), 3.79-3.76 (m, 4H), 3.46-3.42 (m, 4H) 55 6-{[2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)phenyl]- hydroxymethyll- pyridazine-3-carboxylic acid B D A MS: 496.1/498.0 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 13.30 (s, (Cl isotopy, rel. peak 1H), 9.11 (s, 1H), 8.21 (d, J = 8.7, 1H), 7.99 (d, intensity ratio [%] 100:36) J = 8.7, 1H), 7.87 (d, J = 7.6, 1H), 7.71 (d, J = 9.5, 1H), 7.55 (qd, J = 9.4, 2.7, 2H), 7.20 (d, J = 2.3, 1H), 7.08-6.66 (m, 1H), 6.42(s, 1H), 3.80-3.75 (m, 4H), 3.49-3.44 (m, 4H) 56 [2-Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- imidazo[1,2-b]pyridazin- 6-ylmethanol (Ena 2) B B C MS: 491.1/493.1 (M + H.sup.+) see racemate (Cl isotopy, rel. peak intensity ratio [%] 100:34); R.sub.t 13.59 min (SFC, Chiralpak AD-H, CO.sub.2/ 40% by vol. of methanol, 0.5% by vol. of diethylamine) 57 [2-Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- imidazo[1,2-b]pyridazin- 6-ylmethanol (Ena 1) A A C MS: 491.1/493.1 (M + H.sup.+) see racemate (Cl isotopy, rel. peak intensity ratio [%] 100:36); R.sub.t 3.87 min (SFC, Chiralpak AD-H, CO.sub.2/ 40% by vol. of methanol, 0.5% by vol. of diethylamine) 58 0 6-{[2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)phenyl]- hydroxymethyl}- pyridazine-3-carboxylic acid methyl ester B C A MS: 510.1/512.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, 1H), (Cl isotopy, rel. peak 8.23 (d, J = 8.7, 1H), 8.01 (d, J = 8.7, 1H), 7.86 (d, intensity ratio [%] 100:33) J = 7.6, 1H), 7.70 (d, J = 9.5, 1H), 7.55 (qd, J = 9.4, 2.8, 2H), 7.20 (d, J = 2.4, 1H), 6.94-6.81 (m, 1H), 6.42 (s, 1H), 3.94 (s, 3H), 3.81-3.75 (m, 4H), 3.48-3.42 (m, 4H) 59 6-{[2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)phenyl]- hydroxymethyl}-2- methyl-2H-pyridazin-3- one A B B MS: 482.1/484.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, 1H), (Cl isotopy, rel. peak 7.92 (d, J = 7.7, 1H), 7.68 (d, J = 9.5, 1H), 7.59 (dd, intensity ratio [%] 100:45) J = 9.4, 3.1, 1H), 7.55 (dd, J = 9.4, 2.5, 1H), 7.49 (d, J = 9.6, 1H), 7.21 (d, J = 2.4, 1H), 6.95 (d, J = 9.6, 1H), 6.68 (d, J = 4.8, 1H), 5.90 (d, J = 3.6, 1H), 3.80- 3.77 (m, 4H), 3.61-3.58 (m, 3H), 3.45 (s, 4H) 60 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (5-methoxypyrazin-2- yl)methanol C B B MS: 448.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.39-8.38 (m, 1H), 8.23 (d, J = 1.3, 1H), 7.66- 7.61 (m, 2H), 7.55-7.50 (m, 2H), 7.40-7.35 (m, 1H), 7.21-7.18 (m, 1H), 6.30 (d, J = 4.4, 1H), 5.88 (d, J = 4.4, 1H), 3.89 (s, 3H), 3.80-3.75 (m, 4H), 3.46-3.42 (m, 4H) 61 [4-methoxy-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (5-methoxypyrazin-2- yl)methanol D D A MS: 460.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.04 (s, 1H), 8.36-8.35 (m, 1H), 8.20 (d, J = 1.4, 1H), 7.53 (dd, J = 8.6, 2.3, 1H), 7.44 (dd, J = 9.4, 2.5, 1H), 7.38 (d, J = 9.4, 1H), 7.35 (d, J = 2.2, 1H), 7.17 (d, J = 8.6, 1H), 7.14 (d, J = 2.5, 1H), 6.13 (d, J = 4.4, 1H), 5.79 (d, J = 4.4, 1H), 3.88 (s, 3H), 3.79-3.75 (m, 4H), 3.66 (s, 3H), 3.43-3.38 (m, 4H) 62 6-{[2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)phenyl]- hydroxymethyl}- pyridazine-3-carboxylic acid amide B B A MS: 495.1/497.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, 1H), (Cl isotopy, rel. peak 8.49 (s, 1H), 8.20 (d, J = 8.7, 1H), 8.00 (d, J = 8.7, intensity ratio [%] 100:35) 1H), 7.91-7.85 (m, 2H), 7.69 (d, J = 9.5, 1H), 7.59- 7.51 (m, 2H), 7.21 (d, J = 2.2, 1H), 6.84 (d, J = 5.0, 1H), 6.42 (d, J = 5.0, 1H), 3.80-3.75 (m, 4H), 3.48- 3.42 (m, 4H) 63 [2-Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- imidazo[1,2-b]pyridazin- 6-ylmethanol A B C MS: 491.1/493.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.13 (s, 1H), (Cl isotopy, rel. peak 8.27-8.25 (m, 1H), 8.11 (dd, J = 9.4, 0.7, 1H), 8.00 intensity ratio [%] 100:38) (d, J = 7.7, 1H), 7.77 (d, J = 1.2, 1H), 7.70 (d, J = 9.5, 1H), 7.61 (dd, J = 9.4, 3.3, 1H), 7.55 (dd, J = 9.4, 2.5, 1H), 7.30 (d, J = 9.5, 1H), 7.22 (d, J = 2.5, 1H), 6.81 (d, J = 4.5, 1H), 6.15 (d, J = 4.2, 1H , 3.81-3.75 (m, 4H), 3.48-3.44 (m, 4H) 64 [2-Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (3-chloropyrazin-2-yl)- methanol B A C MS: 486.1/488.1/490.0 1H NMR (500 MHz, DMSO-d6) ppm = 9.14(s, 1H), (M + H.sup.+) (Cl.sub.2 isotopy, rel. 8.61 (d, J = 2.4, 1H), 8.49 (d, J = 2.4, 1H), 8.00 (d, peak intensity ratio [%] J = 7.7, 1H), 7.66 (d, J = 9.5, 1H), 7.64-7.55 (m, 100:63:11) 2H), 7.22 (d, J = 2.4, 1H), 6.70 (d, J = 6.0, 1H), 6.42 (d, J = 6.0, 1H), 3.81-3.76 (m, 4H), 3.49-3.44 (m, 4H) 65 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- pyridazin-3-ylmethanol C B A MS: 418.3 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (dd, J = 4.9, 1.7, 1H), 9.09 (s, 1H), 7.83 (dd, J = 8.6, 1.7, 1H), 7.72-7.65 (m, 3H), 7.52-7.49 (m, 2H), 7.42- 7.37 (m, 1H), 7.21-7.18 (m, 1H), 6.56 (d, J = 4.3, 1H), 6.12-6.09 (m, 1H), 3.80-3.75 (m, 4H), 3.46- 3.41 (m, 4H) 66 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (5-methoxypyrimidin-2- yl)methanol (Ena 2) C D A MS: 448.1 (M + H.sup.+); R.sub.t 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 53.23 min, (HPLC, 8.53 (s, 2H), 7.70 - 7.63 (m, 2H), 7.52 (s, 2H), Chiralpak AD-H, ethanol) 7.40-7.32 (m, 1H), 7.22-7.15 (m, 1H), 6.06 (d, J = 5.5, 1H), 5.86 (d, J = 5.5, 1H), 3.89 (s, 3H), 3.79- 3.76 (m, 4H), 3.45-3.43 (m, 4H) 67 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (5-methoxypyrimidin-2- yl)methanol (Ena 1) C C A MS: 448.1 (M + H.sup.+); R.sub.t 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 45.79 min,(HPLC, 8.53 (s, 2H), 7.70-7.63 (m, 2H), 7.52 (s, 2H), Chiralpak AD-H,ethanol) 7.40-7.32 (m, 1H), 7.22-7.15 (m, 1H), 6.06 (d, J = 5.5, 1H), 5.86 (d, J = 5.5, 1H), 3.89 (s, 3H), 3.79- 3.76 (m, 4H), 3.45-3.43 (m, 4H) 68 0 (6-Dimethylamino- pyridazin-3-yl)-[4-fluoro- 3-(7-morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol B C A MS: 461.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 7.65-7.56 (m, 2H), 7.55-7.48 (m, 2H), 7.43- 7.34 (m, 2H), 7.24-7.17 (m, 1H), 7.07 (d, J = 9.4, 1H), 6.27 (d, J = 4.4, 1H), 5.93 (d, J = 4.4, 1H), 3.81- 3.75 (m, 4H), 3.47-3.41 (m, 4H), 3.06 (s, 6H) 69 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (5-methoxypyrimidin-2- yl)methanol B C A 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.53 (s, 2H), 7.70-7.63 (m, 2H), 7.52 (s, 2H), MS: 448.1 (M + H.sup.+) 7.40-7.32 (m, 1H), 7.22-7.15 (m, 1H), 6.06 (d, J = 5.5, 1H), 5.86 (d, J = 5.5, 1H), 3.89 (s, 3H), 3.79 - 3.76 (m, 4H), 3.45-3.43 (m, 4H) 70 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (6-methylpyridazin-3- yl)methanol B B A MS:432.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 7.72-7.61 (m, 3H), 7.58-7.47 (m, 3H), 7.43- 7.33(m, 1H), 7.22-7.16 (m, 1H), 6.50 (d, J = 4.0, 1H), 6.07 (d, J = 3.8, 1H), 3.77 (t, J = 5.9, 3.9, 4H), 3.44 (t, J = 4.9, 4H), 2.58 (s, 3H) 71 (R)-[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (6-methoxypyridazin-3- yl)methanol A B A MS: 448.1 (M + H.sup.+); Rt 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 24.02 min, (SFC, Chiralcel 7.70 (d, J = 9.2, 1H), 7.66-7.61 (m, 2H), 7.53- OJ-H, CO.sub.2/15% by vol. of 7.50 (m, 2H), 7.42-7.37 (m, 1H), 7.22-7.19 (m, 2-propanol, 0.5% by vol. 2H), 6.48 (d, J = 4.4, 1H), 6.02 (d, J = 4.4, 1H), 4.00 of diethylamine) (s, 3H), 3.80-3.75 (m, 4H), 3.46-3.41 (m, 4H) 72 (S)-[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (6-methoxypyridazin-3- yl)methanol A B A MS: 448.1 (M + H.sup.+); Rt 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 19.10 min, (SFC, Chiralcel 7.69 (d, J = 9.2, 1H), 7.66-7.61 (m, 2H), 7.53- OJ-H, CO.sub.2/15% by vol. of 7.50 (m, 2H), 7.41-7.37 (m, 1H), 7.21-7.19 (m, 2-propanol, 0.5% by vol. 2H), 6.48 (d, J = 4.4, 1H), 6.02 (d, J = 4.4, 1H), 4.00 of diethylamine) (s, 3H), 3.79-3.76 (m, 4H), 3.46-3.42 (m, 4H) 73 4-{2-Fluoro-5-[methoxy- (6-methoxy-pyridazin-3- yl)methyl]phenyl}-7- morpholin-4-yl- quinazoline B B A MS: 462.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 7.69 (d, J = 9.1, 1H), 7.65-7.61 (m, 2H), 7.54- 7.48 (m, 2H), 7.45-7.40 (m, 1H), 7.23 (d, J = 9.2, 1H), 7.21-7.19 (m, 1H), 5.71 (s, 1H), 4.01 (s, 3H), 3.80-3.75 (m, 4H), 3.47-3.41 (m, 4H), 3.36 (s, 3H) 74 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (6-methoxypyridazin-3- yl)methanol A A A MS: 448.1 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 7.69 (d, J = 9.2, 1H), 7.67-7.61 (m, 2H), 7.54- 7.48 (m, 2H), 7.42-7.36 (m, 1H), 7.22-7.17 (m, 2H), 6.51-6.45 (m, 1H), 6.04 - 6.00 (m, 1H), 4.00 (s, 3H), 3.80-3.74 (m, 4H), 3.47-3.41 (m, 4H) 75 6-({4-Fluoro-3-[7-(3- oxa-8-aza-bicyclo- [3.2.1]oct-8-yl)- quinazolin-4-yl]phenyl}- hydroxymethyl)-2H- pyridazin-3-one D A MS: 460.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 12.88- 12.84 (m, 1H), 9.04 (s, 1H), 7.63-7.57 (m, 2H), 7.50-7.45 (m, 2H), 7.44-7.38 (m, 2H), 7.14 (d, J = 2.4, 1H), 6.87 (dd, J = 9.8, 2.2, 1H), 6.42 (d, J = 4.4, 1H), 5.68-5.64 (m, 1H), 4.55-4.46 (m, 2H), 3.69 (d, J = 10.9, 2H), 3.54 (d, J = 10.4, 2H), 2.09-1.94 (m, 4H) 76 6-([4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- hydroxymethyl}-2H- pyridazin-3-one (Ena 2) A B A MS: 434.1 (M + H.sup.+); R.sub.t 1H NMR (400 MHz, DMSO-d6) ppm = 12.86 (s, 16.74 min, (SFC, Chiralcel 1H), 9.10 (s, 1H), 7.64-7.58 (m, 2H), 7.55-7.50 OJ-H, CO.sub.2/15% by vol. of (m, 2H), 7.48 (d, J = 9.8, 1H), 7.45-7.38 (m, 1H), methanol, 0.5% by vol. of 7.23-7.16 (m, 1H), 6.87 (d, J = 9.8, 1H), 6.44 (d, diethylamin) J = 4.3, 1H), 5.70-5.62 (m, 1H), 3.81-3.74 (m, Ena 1 to this compound: 4H), 3.47-3.41 (m, 4H) Example 367 77 (3-Chloro-5-fluoro- pyridin-4-yl)-[4-fluoro-3- (7-morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol B A C MS: 469.1/471.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), (Cl isotopy, rel. peak 8.58-8.53 (m, 2H), 7.65-7.56 (m, 2H), 7.56- intensity ratio [%] 100:31) 7.47(m, 2H), 7.46-7.38 (m, 1H), 7.23-7.17(m, 1H), 6.65 (d, J = 4.7, 1H), 6.33 (d, J = 4.7, 1H), 3.80- 3.75 (m, 4H), 3.47-3.41 (m, 4H) 78 00 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- (3-methylpyrazin-2-yl)- methanol B A B MS: 432.2 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.43 (s, 2H), 7.63-7.55 (m, 2H), 7.55-7.50 (m, 2H), 7.42-7.34 (m, 1H), 7.22-7.17 (m, 1H), 6.28 (d, J = 5.5, 1H), 6.08 (d, J = 5.4, 1H , 3.81-3.74 (m, 4H), 3.48-3.40 (m, 4H), 2.58-2.53 (m, 3H) 79 01 (5-Ethoxypyridazin-3- yl)-[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- methanol D C B MS: 462.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.84 (d, J = 2.9, 1H), 7.72-7.66 (m, 2H), 7.52-7.49 (m, 2H), 7.41-7.36 (m, 1H), 7.30 (d, J = 2.9, 1H), 7.21-7.18 (m, 1H), 6.52 (d, J = 4.5, 1H), 6.04 (d, J = 4.5, 1H), 4.26-4.16 (m, 2H), 3.81-3.74 m, 4H), 3.48-3.40 (m, 4H), 1.34 (t, J = 6.9, 3H). 80 02 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-trifluoro- methylpyridin-2-yl)- methanol B B A MS:485.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 8.90 - 8.85 (m, 1H), 8.20 (dd, J = 8.1, 1.6, 1H), 7.63 (dd, J = 6.9, 2.3, 1H), 7.60-7.51 (m, 4H), 7.38 (dd, J = 9.9, 8.6, 1H), 7.21-7.18 (m, 1H), 6.32 (d, J = 6.3, 1H), 6.12 (d, J = 6.0, 1H), 3.81-3.74 (m, 4H), 3.47-3.41 (m, 4H). 81 03 (3-Difluoromethoxy- pyridin-2-yl)-[4-fluoro- 3-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol A A A MS:483.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.46 (dd, J = 4.6, 1.3, 1H), 7.67-7.64 (m, 1H), 7.62- 7.57 (m, 2H), 7.54-7.49 (m, 2H), 7.42 (dd, J = 8.3, 4.6, 1H), 7.40-7.10 (m, 3H), 6.14-6.07 (m, 2H), 3.81-3.75 (m, 4H), 3.47-3.41 (m, 4H). 82 04 (S)-[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)methanol C B A MS:432.2(M + H.sup.+) ; ); R.sub.t 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 12.50 min (SFC, ChiralPak 8.44 (s, 2H), 7.64-7.51 (m, 4H), 7.44-7.35 (m, AD-H, Cl.sub.2/25% by vol. 1H), 7.20 (s, 1H), 6.31 (d, J = 5.5, 1H), 6.09 (d, of 2-propanol, 0.5% by J = 5.4, 1H), 3.81-3.74 (m, 4H), 3.48-3.40 (m, vol. of diethylamine) 4H), 2.56 (s, 3H). 83 05 (R)-[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)methanol A A A MS: 432.1 (M + H.sup.+); R.sub.t 1H NMR (400 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 19.51 min (SFC, ChiralPak 8.43 (s, 2H), 7.63-7.49 (m, 4H), 7.43-7.34 (m, AD-H, CO.sub.2/25% by vol. 1H), 7.19 (s, 1H), 6.28 (d, J = 5.5, 1H), 6.08 (d, of 2-propanol, 0.5% by J = 5.4, 1H), 3.82-3.73 (m, 4H), 3.48-3.40 (m, vol. of diethylamine) 4H), 2.55 (s, 3H). 84 06 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)methanol B A B MS: 450.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, 1H), 8.45 (d, J = 2.5, 1H), 8.39 (dd, J = 2.5, 0.8, 1H), 7.89 (t, J = 8.2, 1H), 7.61 (dd, J = 9.4, 3.2, 1H), 7.56 (dd, J = 9.4, 2.5, 1H), 7.40 (t, J = 10.1, 1H), 7.21 (d, J = 2.4, 1H), 6.39-6.35 (m, 1H), 6.27 (s, 1H), 3.81- 3.75 (m, 4H), 3.49-3.43 (m, 4H), 2.67 (s, 3H). 85 07 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)methanol (Ena 1) A B B MS: 450.2 (M + H.sup.+) ; R.sub.t see racemate 3.45 min (SFC, ChiralPak AD-H, CO.sub.2/30% by vol. of methanol, 0.5% by vol. of diethylamine) 86 08 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)methanol (Ena 2) A A A MS: 450.2 (M + H.sup.+) ; Rt see racemate 5.60 min (SFC, ChiralPak AD-H, CO.sub.2/25% by vol. of methanol, 0.5% by vol. of diethylamine) 87 09 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(5-methoxy- pyrimidin-4-yl)- methanol A A B MS: 448.1 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) pp = 9.11 (s, 1H), 8.82 (s, 1H), 8.58 (s, 1H), 7.67-7.61 (m, 2H), 7.55-7.52 (m, 2H), 7.41-7.34 (m, 1H), 7.23- 7.19(m, 1H), 6.13 (d, J = 6.1, 1H), 6.07 (d, J = 6.2, 1H), 3.95 (s, 3H), 3.83-3.76 (m, 4H), 3.49-3.42 (m, 4H). 88 0 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3,6-dimethyl- pyrazin-2-yl)methanol A A B MS: 464.2 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.13 (s, 1H), 8.35 (s, 1H), 7.88 (t, J = 8.2, 1H), 7.61 (dd, J = 9.4, 3.0, 1H), 7.56 (dd, J = 9.5, 2.5, 1H), 7.42 (t, J = 10.2, 1H), 7.23 (d, J = 2.4, 1H), 6.31 (d, J = 5.9, 1H), 6.22 (d, J = 5.6, 1H), 3.85-3.75 (m, 4H), 3.51-3.43 (m, 4H), 2.58 (s, 3H), 2.40 s, 3H). 89 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thieno,2-d}- pyrimidin-4-ylmethanol B A C MS: 490.1/492.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.06 (s, 1H), (Cl isotopy, rel. peak 9.04 (s, 1H), 8.47 (d, J = 5.6, 1H), 7.89 (d, J = 2.1, intensity ratio [%] 100:43) 1H), 7.76 (d, J = 9.4, 1H), 7.73 (dd, J = 8.2, 2.2, 1H), 7.69 (d, J = 8.2, 1H), 7.62 (d, J = 5.6, 1H), 7.47 (dd, J = 9.5, 2.6, 1H), 7.20-7.16 (m, 2H), 6.47 (d, J = 4.9, 1H), 3.81-3.74 (m, 4H), 3.47-3.39 (m, 4H). 90 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thieno[2,3-d}- pyrimidin-4-ylmethanol A A A MS: 492.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.07 (s, 1H), 9.05 (s, 1H), 8.47 (d, J = 5.6, 1H), 7.76 (t, J = 8.0, 1H), 7.61 (d, J = 5.6, 1H), 7.55-7.46 (m, 3H), 7.20- 7.17 (m, 2H), 6.32 (d, J = 4.7, 1H), 3.81-3.74 (m, 4H), 3.47-3.41 (m, 4H). 91 6-([4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1-methyl-1H- pyridin-2-one A A A MS: 447.2 (M + H.sup.+) 1H- NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 7.60-7.56 (m, 2H), 7.55-7.51 (m, 2H), 7.48- 7.43 (m, 1H), 7.40 (dd, J = 9.1, 6.9, 1H), 7.21-7.19 (m, 1H), 6.52 (d, J = 5.3, 1H), 6.36 (dd, J = 9.1, 1.4, 1H), 6.25 (dd, J = 7.0, 1.4, 1H), 5.94 (d, J = 5.1, 1H), 3.80-3.75 (m, 4H), 3.47-3.41 (m, 4H), 3.38 (s, 3H).

Examples 92 and 93

3-[[2-Chloro-4-fluoro-5-(7-morpholinylquinazolin-4-yl)phenyl]hydroxymethyl]-1H-pyridazin-6-one (92)

6-{[2-Chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]hydroxymethyl}-2-ethyl-2H-pyridazin-3-one (93)

(87) ##STR00114##

(88) [2-Chloro-4-fluoro-5-(7-morpholinylquinazolin-4-yl)phenyl]-(6-chloropyridazin-3-yl)methanone, starting from 2,6-dichloropyridazine and 2-[2-chloro-4-fluoro-5-(7-morpholinylquinazolin-4-yl)phenyl]acetonitrile, and 3-[[2-chloro-4-fluoro-5-(7-morpholinylquinazolin-4-yl)phenyl]-hydroxymethyl]-1H-pyridazin-6-one (EXAMPLE 92) were prepared analogously to the synthetic processes described under EXAMPLES 1 and 2.

Preparation of 3-[2-chloro-4-fluoro-5-(7-morpholinylquinazolin-4-yl)benzoyl]-1H-pyridazin-6-one from [2-chloro-4-fluoro-5-(7-morpholinylquinazolin-4-yl)phenyl]-(6-chloropyridazin-3-yl)methanone

(89) [2-Chloro-4-fluoro-5-(7-morpholinylquinazolin-4-yl)phenyl]-(6-chloropyridazin-3-yl)methanone (2.0 g, 4.13 mmol) was dissolved in 1,4-dioxane (80 ml, max. 0.005% of water) under an argon atmosphere. 3-Hydroxypropionitrile (570 l ml, 8.27 mmol) and sodium hydride (60% dispersion in paraffin oil) (215 mg; 5.37 mmol) were subsequently added (evolution of gas). The reaction mixture was stirred at room temperature for 2 h. After termination of the reaction, the mixture was carefully diluted with water (100 ml) and neutralised using hydrochloric acid (1.0 M). The aqueous phase was subsequently extracted twice with ethyl acetate (200 ml in each case). The combined organic phases were washed with saturated sodium chloride solution, subsequently dried over sodium sulfate, filtered and evaporated to dryness in a rotary evaporator. The residue was purified by means of flash column chromatography (dichloromethane/0-10% by vol. of ethanol, CombiFlash Rf 200), giving 3-[2-chloro-4-fluoro-5-(7-morpholinylquinazolin-4-yl)benzoyl]-1H-pyridazin-6-one (695 mg, 1.47 mmol, MS: 466.1/468.1 [M+H.sup.+]), 36% yield) as solid.

Preparation of 6-{[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]hydroxymethyl}-2-ethyl-2H-pyridazin-3-one (EXAMPLE 93) from 3-[[2-chloro-4-fluoro-5-(7-morpholinylquinazolin-4-yl)phenyl]hydroxymethyl]-1H-pyridazin-6-one (EXAMPLE 92)

(90) 3-[[2-Chloro-4-fluoro-5-(7-morpholinylquinazolin-4-yl)phenyl]hydroxymethyl]-1H-pyridazin-6-one (150 mg; 0.316 mmol) was dissolved in N,N-dimethylformamide (5.0 ml). Iodoethane (52 l, 0.632 mmol) and potassium carbonate (132 mg, 0.947 mmol) were subsequently added. The reaction mixture was stirred at room temperature for 6 h. After termination of the reaction, the mixture was decanted off onto water (100 ml). The aqueous phase was subsequently extracted twice with ethyl acetate (100 ml in each case). The combined organic phases were rinsed with water (40 ml), subsequently dried over sodium sulfate, filtered us evaporated to dryness in vacuo. The residue was suspended in acetone and filtered off with suction. The filter cake was dried at room temperature in a high vacuum, giving 6-{[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]hydroxymethyl}-2-ethyl-2H-pyridazin-3-one (EXAMPLE 93, 157 mg, 0.31 mmol, MS: 496.1/498.1 [M+H.sup.+], 97% yield) as solid.

(91) Compounds which were prepared in accordance with EXAMPLE 93 can be found in Table 2 below.

(92) TABLE-US-00002 TABLE 2 Compounds of the formula (I) IC.sub.50 IC.sub.50 K.sub.i DNA- pDNA- [Kv1.11 No. Structural formula Name PK PK hERG][ 92 3-[[2-Chloro-4-fluoro-5- (7-morpholino- quinazolin-4-yl)phenyl]- hydroxymethyl]-1H- pyridazin-6-one A A A MS: 468.1/470.0 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 12.89 (d, (Cl isotopy, rel. peak J = 2.4, 1H), 9.12 (s, 1H), 7.92 (d, J = 7.7, 1H), 7.68 intensity ratio [%] 100:38) (d, J = 9.5, 1H), 7.59-7.55 (m, 2H), 7.53 (d, J = 9.8, 1H), 7.21 (d, J = 2.2, 1H), 6.90 (dd, J = 9.8, 2.3, 1H), 6.61 (d, J = 5.1, 1H), 5.89 (d, J = 5.1, 1H), 3.81-3.76 (m, 4H), 3.48-3.44 (m, 4H) 93 6-{[2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)phenyl]- hydroxymethyl}-2-ethyl- 2H-pyridazin-3-one B A C MS: 496.1/498.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.13 (s, 1H), (Cl isotopy, rel. peak 7.94 (d, J = 7.7, 1H), 7.68 (d, J = 9.5, 1H), 7.59-7.52 intensity ratio [%] 100:41) (m, 2H), 7.46 (d, J = 9.6, 1H), 7.22 (d, J = 2.3, 1H), 6.92 (d, J = 9.6, 1H), 6.61 (d, J = 4.8, 1H), 5.90 (d, J = 4.8, 1H), 4.08-3.95 (m, 2H), 3.81-3.74 (m, 4H), 3.49-3.41 (m, 4H), 1.20 (t, J = 7.2 3H) 94 2-(2-Amino-ethyl)-6-{[2- Chloro-4-fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)phenyl]- hydroxymethyl}-2H- pyridazin-3-one C D A MS: 511.1/513.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.13 (s, 1H), (Cl isotopy, rel. peak 7.94 (d, J = 7.7, 1H), 7.68 (d, J = 9.5, 1H), 7.60-7.52 intensity ratio [%] 100:38) (m, 2H), 7.48 (d, J = 9.7, 1H), 7.21 (d, J = 2.2, 1H), 6.94 (d, J = 9.6, 1H), 6.72-6.57 (m, 1H), 5.91 (s, 1H), 4.10-3.96 (m, 2H), 3.82-3.73 (m, 4H), 3.48- 3.43 (m, 4H), 2.88 (t, J = 6.6, 2H) 95 6-{[2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)phenyl]- hydroxymethyl}-2- cyclopropyl-2H- pyridazin-3-one C B A MS: 508.1/510.1 (M + H.sup.+) 1H NMR (400 MHz, Methylenchlorid-d2) ppm = 9.04 (Cl isotopy, rel. peak (s, 1H), 7.71 (d, J = 7.6, 1H), 7.49 (dd, J = 9.3, 3.5, intensity ratio [%] 100:38) 1H), 7.26-7.20 (m, 2H), 7.18-7.14 (m, 2H), 6.74 (d, J = 9.6, 1H), 5.97 (s, 1H), 4.03-3.94 (m, 1H), 3.82-3.74 (m, 4H), 3.39-3.31 (m, 4H), 0.98-0.82 (m, 4H) 96 6{[2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)phenyl]- hydroxymethyl}-2-ethyl- 2H-pyridazin-3-one (Ena 2) C B A MS: 496.2/498.1 (M + H.sup.+) see racemate (Cl isotopy, rel. peak intensity ratio [%] 100:34); R.sub.t 4.59 min (SFC, Chiracel OJ-H, CO.sub.2/20% by vol. of methanol, 0.5% by vol. of diethylamine) 97 0 6-{[2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)phenyl]- hydroxymethyl}-2-ethyl- 2H-pyridazin-3-one (Ena 1) A B A MS: 496.2/498.1 (M + H.sup.+) see racemate (Cl isotopy, rel. peak intensity ratio [%] 100:36); R.sub.t 3.00 min (SFC, Chiracel OJ-H, CO.sub.2/20% by vol. of methanol, 0.5% by vol. of diethylamine) 98 2-(3-{[2-Chloro-4- fluoro-5-(7-morpholin- 4-ylquinazolin-4-yl)- phenyl]hydroxymethyl}- 6-oxo-6H-pyridazin-1- yl)acetamide B D A MS: 525.1/527.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, 1H), (Cl isotopy, rel. peak 7.93 (d, J = 7.7, 1H), 7.67 (d, J = 9.5, 1H), 7.58 (dd, intensity ratio [%] 100:36) J = 9.4, 3.0, 1H), 7.53 (dd, J = 9.5, 2.5, 1H), 7.51- 7.44 (m, 2H), 7.21 (d, J = 2.4, 1H), 7.15 (s, 1H), 6.94 (d, J = 9.6, 1H), 6.62 (d, J = 4.8, 1H), 5.89 (d, J = 4.8, 1H), 4.61-4.51 (m, 2H), 3.81-3.75 (m, 4H), 3.48-3.42 (m, 4H) 99 6-{[2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)phenyl]- hydroxymethyl}-2-(2- hydroxy-ethyl)-2H- pyridazin-3-one B B A MS: 512.2/514.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.13 (s, 1H), (Cl isotopy, rel. peak 7.94 (d, J = 7.7, 1H), 7.68 (d, J = 9.5, 1H), 7.60-7.52 intensity ratio [%] 100:38) (m, 2H), 7.46 (d, J = 9.6, 1H), 7.22 (d, J = 2.3, 1H), 6.92 (d, J = 9.6, 1H), 6.61 (d, J = 4.8, 1H), 5.90 (d, J = 4.8, 1H), 4.75 (t, J = 5.8, 1H), 4.11-4.00 (m, 2H), 3.82-3.74 (m, 4H), 3.65 (q, J = 6.2, 2H), 3.49-3.42 (m, 4H)

Example 100

[2-Chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-[6-(oxetan-3-yloxy)pyridazin-3-yl]methanol (100)

(93) ##STR00123##

(94) [2-Chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-chloropyridazin-3-yl)methanone (700 mg, 1.30 mmol) and oxetan-3-ol (112 mg, 1.43 mmol) were initially introduced dissolved in 1,4-dioxane (25 ml, max. 0.005% of water) under an argon atmosphere. Sodium hydride (60% dispersion in paraffin oil, 62 mg, 1.56 mmol) was subsequently added (evolution of gas). The reaction mixture was stirred at room temperature for 30 min. After termination of the reaction, the mixture was carefully diluted with water (80 ml) and neutralised using hydrochloric acid (1.0 M). The aqueous phase was subsequently extracted twice with ethyl acetate (80 ml in each case). The combined organic phases were rinsed with water (20 ml), subsequently dried over sodium sulfate, filtered and evaporated to dryness in a rotary evaporator. The residue was purified by means of flash column chromatography (dichloromethane/0-10% by vol. of ethanol, CombiFlash Rf 200), giving [2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-[6-(oxetan-3-yloxy)pyridazin-3-yl]methanone (264 mg, 0.506 mmol, 522.2 [M+H.sup.+]), 39% yield) as solid.

(95) [2-Chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-[6-(oxetan-3-yloxy)pyridazin-3-yl]methanol (EXAMPLE 100) was prepared analogously to the synthetic process described under EXAMPLES 1 and 2 starting from [2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-[6-(oxetan-3-yloxy)pyridazin-3-yl]methanone.

(96) Compounds which were prepared in accordance with EXAMPLE 100 can be found in Table 3 below.

(97) TABLE-US-00003 TABLE 3 Compounds of the formula (I) IC.sub.50 IC.sub.50 K.sub.i DNA- pDNA- [Kv1.11 No. Structural formula Name PK PK hERG] 100 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-[6-(oxetan-3- yloxy)pyridazin-3-yl]- methanol A A C MS: 524.2/526.1 (M + H.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, isotopy, rel. peak intensity ratio 1H), 7.91 (d, J = 7.7, 1H), 7.77 (d, J = 9.2, 1H), [%] 100:39) 7.66 (d, J = 9.4, 1H), 7.61-7.51 (m, 2H), 7.32 (d, J = 9.2, 1H), 7.21 (d, J = 2.3, 1H), 6.63 (d, J = 4.8, 1H), 6.22 (d, J = 4.8, 1H), 5.69 (p, J = 5.7, 1H), 4.94-4.87 (m, 2H), 4.62-4.56 (m, 2H), 3.80-3.76 (m, 4H), 3.48-3.43 (m, 4H) 101 2-(6-{[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}pyridazin-3- yloxy)propionitrile A A C MS: 521.2/523.2 (M + H.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (d, isotopy, rel. peak intensity ratio J = 2.7, 1H), 7.93 (dd, J = 11.2, 7.7, 1H), 7.84 (dd, [%] 100:39) J = 16.3, 9.2, 1H), 7.70-7.65 (m, 1H), 7.63- 7.57 (m, 1H), 7.57-7.51 (m, 1H), 7.38 (dd, J = 9.1, 3.5, 1H), 7.21 (d, J = 2.4, 1H), 6.71 (dd, J = 10.3, 5.0, 1H), 6.28 (dd, J = 9.5, 5.0, 1H), 5.95- 5.87 (m, 1H), 3.81-3.74 (m, 4H), 3.48-3.42 (m, 4H), 1.76-1.70 (m, 3H) 102 2-(6-{[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}pyridazin-3- yloxy)propionitrile (eluate 1) A A B MS: 543.0/545.0 (M + Na.sup.+) (Cl see also diastereomer mixture isotopy, rel. peak intensity ratio [%] 100:35); R.sub.t 4.09 min (SFC, Chiralpak AS-H, CO.sub.2/20% by vol. of methanol, 0.5% by vol. of diethylamine) 103 2-(6-{[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}pyridazin-3- yloxy)propionitrile (eluate 3) D D A MS: 521.1/523.1 (M + H.sup.+) (Cl see also diastereomer mixture isotopy, rel. peak intensity ratio [%] 100:38); R.sub.t 6.68 min (SFC, Chiralpak AS-H, CO.sub.2/20% by vol. of methanol, 0.5% by vol. of diethylamine) 104 2-(6-{[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}pyridazin-3- yloxy)propionitrile (eluate 2) C B B MS: 521.1/523.1 (M + H.sup.+) (Cl see also diastereomer mixture isotopy, rel. peak intensity ratio [%] 100:35); R.sub.t 5.12 min (SFC, Chiralpak AS-H, CO.sub.2/20% by vol. of methanol, 0.5% by vol. of diethylamine) 105 2-(3-{[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}pyrazin-2- oxy)ethanol C D A MS: 478.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.19 (d, J = 2.8, 1H), 8.12 (d, J = 2.8, 1H), 7.70-7.64 (m, 2H), 7.54-7.51 (m, 2H), 7.38- 7.33 (m, 1H), 7.21-7.19 (m, 1H), 6.14 (d, J = 5.9, 1H), 6.00 (d, J = 6.0, 1H), 4.86 (t, J = 5.7, 1H), 4.34-4.30 (m, 2H), 3.80-3.75 (m, 4H), 3.74-3.69 (m, 2H), 3.46-3.42 (m, 4H) 106 0 2-(3-{[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}pyrazin-2-yl- amino)ethanol C C B MS: 477.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 7.91 (d, J = 2.7, 1H), 7.67 (d, J = 2.8, 1H), 7.63-7.58 (m, 2H), 7.55-7.49 (m, 2H), 7.41- 7.35 (m, 1H), 7.20 (d, J = 2.0, 1H), 6.82-6.75 (m, 2H), 5.91 (d, J = 4.2, 1H), 4.74 (t, J = 5.1, 1H), 3.82-3.73 (m, 4H), 3.60-3.45 (m, 8H) 107 3-(6-{[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}pyridazin-3-yl- oxy)propionitrile B B A MS: 521.2/523.2 (M + H.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, isotopy, rel. peak intensity ratio 1H), 7.95 (d, J = 7.7, 1H), 7.67 (d, J = 9.5, 1H), [%] 100:39) 7.59 (dd, J = 9.4, 3.2, 1H), 7.55-7.49 (m, 2H), 7.21 (d, J = 2.4, 1H), 6.99 (d, J = 9.6, 1H), 6.67 (d, J = 4.9, 1H), 5.92 (d, J = 4.9, 1H), 4.31-4.17 (m, 2H), 3.81-3.75 (m, 4H), 3.49-3.42 (m, 4H), 2.99-2.88 (m, 2H) 108 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6-methyl- sulfanylpyridazin-3- yl)methanol B A B MS: 498.1/500.1 (M + H.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, isotopy, rel. peak intensity ratio 1H), 7.90 (d, J = 7.7, 1H), 7.68 (d, J = 9.5, 1H), [%] 100:47) 7.66-7.60 (m, 2H), 7.60-7.56 (m, 1H), 7.54 (dd, J = 9.4, 2.5, 1H), 7.21 (d, J = 2.4, 1H), 6.68 (s, 1H), 6.25 (s, 1H), 3.80-3.76 (m, 4H), 3.47- 3.43 (m, 4H), 2.61 (s, 3H) 109 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6-methoxy- 4-methylpyridazin-3- yl)methanol D C A MS: 518.2/520.2 (M + Na.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 9.14 (s, isotopy, rel. peak intensity ratio 1H), 7.99 (d, J = 7.8, 1H), 7.67-7.61 (m, 2H), [%] 100:38) 7.57 (dd, J = 9.4, 2.6, 1H), 7.23 (d, J = 2.5, 1H), 7.10 (d, J = 1.1, 1H), 6.42 (d, J = 6.4, 1H), 6.25 (d, J = 6.3, 1H), 3.96 (s, 3H), 3.82-3.75 (m, 4H), 3.50-3.42 (m, 4H), 2.49-2.46 (m, 3H) 110 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6-methoxy- 5-methylpyridazin-3- yl)methanol C B C MS: 496.1/498.1 (M + H.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, isotopy, rel. peak intensity ratio 1H), 7.91 (d, J = 7.8, 1H), 7.66 (d, J = 9.6, 1H), [%] 100:38) 7.59 (dd, J = 9.4, 3.3, 1H), 7.56-7.52 (m, 2H), 7.21 (d, J = 2.4, 1H), 6.54 (d, J = 4.9, 1H), 6.18 (d, J = 4.9, 1H), 4.02 (s, 3H), 3.80-3.75 (m, 4H), 3.48-3.43 (m, 4H), 2.17 (d, J = 1.0, 3H) 111 2-(6-{[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}pyridazin-3- yloxy)acetamide B C A MS: 525.2/527.2 (M + H.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, isotopy, rel. peak intensity ratio 1H), 7.92 (d, J = 7.7, 1H), 7.74 (d, J = 9.1, 1H), [%] 100:34) 7.66 (d, J = 9.5, 1H), 7.59 (dd, J = 9.4, 3.3, 1H), 7.57-7.49 (m, 2H), 7.27 (d, J= 9.1, 1H), 7.23- 7.16 (m, 2H), 6.63 (d, J = 5.0, 1H), 6.23 (d, J = 5.0, 1H), 4.81 (s, 2H), 3.81-3.75 (m, 4H), 3.49-3.43 (m, 4H) 112 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-[6-(2- methoxyethoxy)- pyridazin-3-yl]- methanol A B B MS: 526.2/528.3 (M + H.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, isotopy, rel. peak intensity ratio 1H), 7.91 (d, J = 7.7, 1H), 7.69 (d, J = 9.2, 1H), [%] 100:38) 7.67 (d, J = 9.5, 1H), 7.59 (dd, J = 9.4, 3.3, 1H), 7.54 (dd, J = 9.5, 2.5, 1H), 7.25-7.19 (m, 2H), 6.61 (d, J = 5.0, 1H), 6.23 (d, J = 5.0, 1H), 4.54- 4.50 (m, 2H), 3.80-3.75 (m, 4H), 3.71-3.67 (m, 2H), 3.48-3.43 (m, 4H), 3.29 (s, 3H) 113 (6-{[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}pyridazin-3-yl- oxy)acetic acid B D A MS: 526.2/528.1 (M + H.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 12.91 (s, isotopy, rel. peak intensity ratio 1H), 9.12 (s, 1H), 7.92 (d, J = 7.7, 1H), 7.75 (d, [%] 100:39) J = 9.1, 1H), 7.66 (d, J = 9.5, 1H), 7.59 (dd, J = 9.4, 3.3, 1H), 7.54 (dd, J = 9.5, 2.5, 1H), 7.31 (d, J = 9.1, 1H), 7.21 (d, J = 2.4, 1H), 6.66 (s, 1H), 6.23 (s, 1H), 4.97 (s, 2H), 3.81-3.75 (m, 4H), 3.48-3.43 (m, 4H) 114 (6-{[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}pyridazin-3-yl- oxy)acetic acid methyl ester B D A MS: 540.2/542.2 (M + H.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, isotopy, rel. peak intensity ratio 1H), 7.92 (d, J = 7.7, 1H), 7.77 (d, J = 9.1, 1H), [%] 100:38) 7.67 (d, J = 9.5, 1H), 7.59 (dd, J = 9.3, 3.2, 1H), 7.57-7.51 (m, 1H), 7.35 (d, J = 9.1, 1H), 7.23- 7.19 (m, 1H), 6.62 (s, 1H), 6.23 (s, 1H), 5.07 (s, 2H), 3.81-3.75 (m, 4H), 3.67 (s, 3H), 3.49- 3.44 (m, 4H) 115 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-[6-(2,2,2- trifluoroethoxy)- pyridazin-3-yl]- methanol B B C MS: 550.2/552.1 (M + H.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, isotopy, rel. peak intensity ratio 1H), 7.91 (d, J = 7.7, 1H), 7.81 (d, J = 9.2, 1H), [%] 100:40) 7.66 (d, J = 9.5, 1H), 7.60-7.52 (m, 2H), 7.41 (d, J = 9.1, 1H), 7.20 (d, J = 2.3, 1H), 6.72 (d, J = 5.0, 1H), 6.26 (d, J = 4.5, 1H, 5.22-5.08 (m, 2H), 3.80-3.75 (m, 4H), 3.47-3.43 (m, 4H) 116 0 2-(6-{[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}pyridazin-3-yl- oxy)ethanol A B A MS: 512.2/514.1 (M + H.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, isotopy, rel. peak intensity ratio 1H), 7.91 (d, J = 7.7, 1H), 7.71-7.64 (m, 2H), [%] 100:38) 7.61-7.51 (m, 2H), 7.23-7.17 (m, 2H), 6.60 (d, J = 5.0, 1H), 6.22 (d, J = 5.0, 1H), 4.84 (t, J = 5.5, 1H), 4.44-4.39 (m, 2H), 3.81-3.76 (m, 4H), 3.74 (q, J = 5.4, 2H), 3.48-3.43 (m, 4H) 117 (3-Amino-pyrazin-2- yl)-[2-chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol B B B MS: 467.1/469.1 (M + H.sup.+) (Cl 1H NMR (400 MHz, DMSO-d6) ppm = 9.14 (s, isotopy, rel. peak intensity ratio 1H), 7.91 (d, J = 7.8, 1H), 7.87 (d, J = 2.7, 1H), [%] 100:34) 7.67-7.55 (m, 4H), 7.21 (d, J = 2.5, 1H), 6.41 (s, 3H), 6.09 (s, 1H), 3.81-3.75 (m, 4H), 3.50- 3.45 (m, 4H) 118 6-{[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}pyridazine-3- carbonitrile B B B MS: 477.0/479.1 (M + H.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, isotopy, rel. peak intensity ratio 1H), 8.36 (d, J = 8.7, 1H), 8.13 (d, J = 8.7, 1H), [%] 100:41) 7.86 (d, J = 7.6, 1H), 7.71 (d, J = 9.5, 1H), 7.55 (qd, J = 9.4, 2.7, 2H), 7.21 (d, J = 2.3, 1H), 6.96 (d, J = 4.9, 1H), 6.43 (d, J = 4.9, 1H), 3.80-3.76 (m, 4H), 3.48-3.43 (m, 4H) 119 (6-{[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}pyridazin-3-yl- oxy)acetonitrile A A B MS: 507.1/509.1 (M + H.sup.+) (Cl 1H NMR (400 MHz, DMSO-d6) ppm = 9.12 (s, isotopy, rel. peak intensity ratio 1H), 7.93 (d, J = 7.7, 1H), 7.85 (d, J = 9.2, 1H), [%] 100:35) 7.67 (d, J = 9.5, 1H), 7.60 (dd, J = 9.4, 3.3, 1H), 7.54 (dd, J = 9.4, 2.5, 1H), 7.40 (d, J = 9.1, 1H), 7.21 (d, J = 2.4, 1H), 6.72 (d, J = 5.0, 1H), 6.28 (d, J = 4.8, 1H), 5.38 (s, 2H), 3.81-3.75 (m, 4H), 3.48-3.42 (m, 4H)

Examples 120, 121 and 122

[2,4-Difluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(4-methoxyphenyl)methanol (EXAMPLE 120)

(98) ##STR00144##

(99) 5-Bromo-2,4-difluorobenzaldehyde (280 mg, 1.27 mmol) in dry tetrahydrofuran (10 ml) was initially introduced in a three-necked flask with internal thermometer, protective-gas inlet, septum and stirrer bar which had been dried by heating. 4-Methoxyphenylmagnesium bromide (1 M in THF, 1.39 ml, 1.39 mmol) was slowly added dropwise at 5 C., and the reaction solution was stirred at room temperature for 18 h. With water (20 ml) was subsequently added to the reaction solution. The phases were separated, and the aqueous phase was extracted twice with ethyl acetate (20 ml). The combined organic phases were washed with water, dried over sodium sulfate, filtered and evaporated to dryness in a rotary evaporator, giving (5-bromo-2,4-difluorophenyl)-(4-methoxyphenyl)methanol (530 mg, 1.61 mmol, MS: 353 [M+H.sup.+]) as oily crude product, which was used without further purification for the next synthesis step.

(100) ##STR00145##

(101) Starting from (5-bromo-2,4-difluorophenyl)-(4-methoxyphenyl)methanol, [2,4-difluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(4-methoxyphenyl)methanol (EXAMPLE 120) was prepared analogously to the synthetic processes described under EXAMPLES 1 and 2.

(6-Difluoromethoxypyridazin-3-yl)-[4-fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-methanol (EXAMPLE 121)

(102) ##STR00146##

(103) 6-Chloro-2H-pyridazin-3-one (944 mg, 7.23 mmol) and difluoro(fluorosulfonyl)acetic acid (1.42 g, 7.96 mmol) were dissolved in acetonitrile (19 ml) in a vessel with stirrer bar and stirred at room temperature for 40 h. The reaction solution was then diluted with ethyl acetate (150 ml) and washed successively with water, saturated sodium hydrogencarbonate solution and again with water. The organic phase was dried using sodium sulfate, filtered and evaporated to dryness in a rotary evaporator. The residue was taken up in cyclohexane, re-filtered, and the solvent was removed in a rotary evaporator. The residue obtained was purified by means of flash column chromatography (gradient cyclohexane/0-50% by vol. of ethyl acetate, CombiFlash Rf 200). The suitable product fractions were combined, and the solvents were removed in a rotary evaporator, giving 3-chloro-6-(difluoromethoxy)pyridazine (285 mg, 1.58 mmol, MS: 181.0/183.1[M+H.sup.+]), 22% yield) as colourless liquid.

(104) ##STR00147##

(105) Potassium hydroxide powder (603 mg, 10.75 mmol) was suspended in dry N,N-dimethylformamide (2 ml) in a glass vessel with stirrer bar and stirred at room temperature for 30 min. (3-Bromo-4-fluorophenyl)acetonitrile (1.0 g, 4.67 mmol), dissolved in N,N-dimethylformamide (1.3 ml), was subsequently added dropwise. The reaction mixture was stirred at room temperature for a further 30 min. (5-Bromo-2,4-difluorophenyl)-(4-methoxyphenyl)methanol (506 mg, 2.80 mmol) was then added in portions to the reaction mixture and stirred at 50 C. for 2 h under an oxygen-free argon protective-gas atmosphere. The reaction mixture was added to a mixture of water (50 ml) and saturated sodium chloride solution (35 ml) and extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and evaporated to dryness in a rotary evaporator. The residue was purified by means of RP column chromatography (gradient water/acetonitrile with 0.1% by vol. of formic acid, CombiFlash Rf 200). The suitable product fractions were combined, and the solvents were removed in a rotary evaporator, giving (3-bromo-4-fluorophenyl)-(6-difluoromethoxypyridazin-3-yl)acetonitrile (146 mg, 0.41 mmol, MS: 358.0/360.0[M+H.sup.30 ], 14% yield) as liquid. 2-(3-Bromo-4-fluorophenyl)-2-(6-chloropyridazin-3-yl)acetonitrile is formed as by-product.

(106) ##STR00148##

(107) (3-Bromo-4-fluorophenyl)-(6-difluoromethoxypyridazin-3-yl)acetonitrile (146 mg, 0.41 mmol) was dissolved in dry acetonitrile (4 ml). Potassium tert-butoxide (43.6 mg, 0.388 mmol) was subsequently added, and the reaction mixture was stirred at room temperature for 25 min. The reaction solution was then cooled to 0 C. in an ice bath, hydrogen peroxide (30% in water, 92 l, 0.90 mmol) was added dropwise, and the reaction mixture was stirred firstly at 0 C. for a further 25 min and then at room temperature for 1 h. For work-up, the reaction mixture was added to water (40 ml) and extracted twice with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and evaporated to dryness in a rotary evaporator, giving (3-bromo-4-fluorophenyl)-(6-difluoromethoxypyridazin-3-yl)methanone (113 mg, 0.32 mmol, MS: 346.9/349.0[M+H.sup.+], 79% yield) as solid.

(108) ##STR00149##

(109) (3-Bromo-4-fluorophenyl)-(6-difluoromethoxypyridazin-3-yl)methanone (126 mg, 0.36 mmol) was dissolved in methanol (4 ml). Sodium borohydride (60.4 mg, 1.60 mmol) was subsequently added in portions, and the reaction mixture was stirred at room temperature for 1 h. After termination of the reaction, the mixture was diluted with saturated ammonium chloride solution (5 ml) and subsequently extracted twice with ethyl acetate (30 ml). The combined organic phases were washed with water, dried over sodium sulfate, filtered and evaporated to dryness in a rotary evaporator, giving (3-bromo-4-fluorophenyl)-(6-difluoromethoxypyridazin-3-yl)methanol (127 mg, MS: 349/351[M+H.sup.+]) as crude product in the form of a solid, which was used without further purification for further synthesis steps.

(6-Difluoromethoxypyridazin-3-yl)-[4-fluoro-3-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-methanol (EXAMPLE 121) was obtained analogously by the synthetic process described for [2,4-difluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(4-methoxyphenyl)methanol (EXAMPLE 120)

1-[2-Chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-1-(6-methoxypyridazin-3-yl)prop-2-yn-1-ol (EXAMPLE 122)

(110) ##STR00150##

(111) ([2-Chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol (EXAMPLE 137, 898 mg, 1.75 mmol) was dissolved in diochloromethane (15 ml). Dess-Martin triacetoxyperiodinane (15% in dichloromethane, 7.23 ml, 3.50 mmol) was subsequently added. The reaction suspension was stirred at room temperature for 1 h. For work-up, water (60 ml) and a 10%, aqueous sodium thiosulfate solution was added. The aqueous phase was extracted twice with ethyl acetate (80 ml in each case). The combined organic phases were washed with saturated sodium chloride solution (30 ml), dried over sodium sulfate, filtered, and the filtrate was evaporated to dryness in vacuo, giving 2.1 g of a crude product in the form of an oil. The residue was purified by means of flash column chromatography (gradient: dichloromethane/0-25% by vol. of dichloromethane/ethanol 9:1, CombiFlash Rf 200), giving [2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanone (792 mg, 1.65 mmol, MS: 480.1/482.1 [M+H.sup.+], 94% yield) as foam.

(112) Trimethylsilylacetylene (179 l, 125 mg, 1.25 mmol) dissolved in dry tetrahydrofuran (3 ml) was initially introduced in a glass vessel with stirrer bar and internal thermometer under argon. The reaction solution was cooled to ()20 C., and n-butyllithium (1.6 M in n-hexane, 781 l, 1.25 mmol) was slowly added dropwise. The reaction mixture was stirred at ()20 C. for a further 30 min. The reaction solution was then cooled to ()70 C., and [2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanone (200 mg, 0.417 mmol) dissolved in dry tetrahydrofuran (6 ml) was subsequently added dropwise. The temperature of the reaction mixture was increased to ()40 C. over a period of 1 h. Water (40 ml) was subsequently added, and the phases were separated. The organic phase was extracted twice with dichloromethane. The combined organic phases were dried using sodium sulfate, filtered and evaporated to dryness in vacuo. The residue was dissolved in dry tetrahydrofuran (4 ml), and tetra-n-butylammonium fluoride trihydrate (109 mg, 0.42 mmol) was added. The mixture was subsequently stirred at room temperature for 18 h. The volatile reaction constituents were then removed in a rotary evaporator. The residue was pre-purified by means of flash column chromatography (gradient: dichloromethane/0-34% by vol. of dichloromethane/ethanol 1:1, CombiFlash Rf 200). The product fractions were combined, and the solvents were removed in vacuo in a rotary evaporator. The residue was finally purified by means of preparative RP chromatography (Chromolith RP-18e 21.2100 mm, flow rate: 50 ml/min., wavelength: 220 nm). The volatile solvent constituents of the suitable fractions were removed by means of a vacuum centrifuge (Genevac HT-12), and the product was freeze-dried from acetonitrile/water (1:3 parts by volume), giving 1-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-1-(6-methoxypyridazin-3-yl)prop-2-yn-1-ol (EXAMPLE 122, 102 mg, 0.20 mmol, MS: 506.1/508.1 [M+H.sup.+], 48% yield) as solid.

(113) Compounds which were prepared in accordance with EXAMPLES 120, 121 and 122 can be found in Table 4 below.

(114) TABLE-US-00004 TABLE 4 Compounds of the formula (I) IC.sub.50 IC.sub.50 K.sub.i DNA- pDNA- [Kv1.11 No. Structural formula Name PK PK hERG] 120 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(4- methoxyphenyl)- methanol C B D MS: 464.2 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 7.61-7.47 (m, 3H), 7.36-7.30 (m, 2H), 7.27 (t, J = 9.1, 1H), 7.20 (d, J = 2.3, 1H), 6.93- 6.87 (m, 2H), 6.18 (d, J = 4.6, 1H), 6.14 (d, J = 4.6, 1H), 3.81-3.75 (m, 4H), 3.73 (s, 3H), 3.48-3.41 (m, 4H) 121 (6-Difluoro- methoxy- pyridazin-3-yl)-[4- fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol B B B MS: 484.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 7.96 (d, J = 9.1, 1H), 7.73-7.63 (m, 2H), 7.57-7.47 (m, 3H), 7.46-7.31 (m, 1H), 7.22- 7.16 (m, 1H), 6.63 (d, J = 4.4, 1H), 6.10 (d, J = 4.4, 1H), 3.81-3.75 (m, 4H), 3.47-3.41 (m, 4H) 122 1-[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-1-(6- methoxy- pyridazin-3-yl)- prop-2-yn-1-ol C B C MS: 506.1/508.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.16 (s, (Cl isotopy, rel. peak intensity 1H), 8.28 (d, J = 7.7, 1H), 7.96 (d, J = 9.2, 1H), ratio [%] 100:35) 7.69-7.63 (m, 2H), 7.59 (dd, J = 9.5, 2.5, 1H), 7.50 (s, 1H), 7.30 (d, J = 9.2, 1H), 7.23 (d, J = 2.5, 1H), 4.02 (s, 3H), 3.94 (s, 1H), 3.81- 3.76 (m, 4H), 3.50-3.44 (m, 4H) 123 1-[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2,2- difluoro-1-(6- methoxy- pyridazin-3-yl)- ethanol C D A MS: 532.1/534.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.15 (s, (Cl isotopy, rel. peak intensity 1H), 8.17 (d, J = 7.7, 1H), 7.67-7.61 (m, 3H), ratio [%] 100:40) 7.57 (dd, J = 9.5, 2.5, 1H), 7.32 (s, 1H, 7.26 (d, 1H), 7.25-7.22 (m, 1H), 7.22-6.96 (m, 2H), 4.05 (s, 3H), 3.81-3.75 (m, 4H), 3.50- 3.45 (m, 4H). 124 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(2-fluoro- 4-methoxy- phenyl)methanol C B D MS: 582.1 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 7.70 (t, J = 8.8, 1H), 7.62-7.44 (m, 3H), 7.25 (t, J = 9.2, 1H), 7.20 (d, J = 2.4, 1H), 6.82 (dd, J = 8.6, 2.5, 1H), 6.74 (dd, J = 12.6, 2.5, 1H), 6.34 (d, J = 4.6, 1H), 6.28 (d, J = 4.6, 1H), 3.82-3.71 (m, 7H), 3.49-3.41 (m, 4H) 125 1-[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-1-(6- methoxy- pyridazin-3-yl)- ethanol B D B MS: 496.1/498.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.15 (s, (Cl isotopy, rel. peak intensity 1H), 8.20 (d, J = 7.9, 1H), 7.67 (dd, J = 9.4, 3.4, ratio [%] 100:35) 1H), 7.60-7.54 (m, 3H), 7.23 (d, J = 2.5, 1H), 7.18 (d, J = 9.2, 1H), 6.39 (s, 1H), 4.03 (s, 3H), 3.82-3.75 (m, 4H), 3.49-3.45 (m, 4H), 2.02 (s, 3H) 126 [2-Chloro-4-fluoro- 5-(6-morpholin-4- ylthieno[3,2-d}- pyrimidin-4-yl)- phenyl]-(6- methoxy- pyridazin-3-yl)- methanol (Ena 2) A A C MS: 488.1/490.1 (M + H.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 8.90 (s, isotopy, rel. peak intensity ratio 1H), 8.00 (d, J = 7.9, 1H), 7.69 (d, J = 9.2, 1H), [%] 100:39); R.sub.t 16.85 min (SFC, 7.66 (d, J = 10.0, 1H), 7.22 (d, J = 9.2, 1H), 6.62 Chiracel OD-H, CO.sub.2/15% by (d, J = 4.9, 1H), 6.54 (s, 1H), 6.22 (d, J = 4.9, vol. of methanol, 0.5% by vol. of 1H), 3.99 (s, 3H), 3.77-3.72 (m, 4H), 3.45- diethylamine) 3.39 (m, 4H) 127 [2-Chloro-4-fluoro- 5-(6-morpholin-4- ylthieno[3,2-d}- pyrimidin-4-yl)- phenyl]-(6- methoxy- pyridazin-3-yl)- methanol (Ena 1) B C C MS: 488.1/490.1 (M + H.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 8.90 (s, isotopy, rel. peak intensity ratio 1H), 8.00 (d, J = 7.9, 1H), 7.69 (d, J = 9.2, 1H), [%] 100:40); R.sub.t 14.73 min (SFC, 7.66 (d, J = 10.0, 1H), 7.22 (d, J = 9.1, 1H), 6.61 Chiracel OD-H, CO.sub.2/15% by (d, J = 5.0, 1H), 6.54 (s, 1H), 6.21 (d, J = 4.9, vol. of methanol, 0.5% by vol. of 1H), 3.99 (s, 3H), 3.77-3.72 (m, 4H), 3.45- diethylamine) 3.40 (m, 4H) 128 [2-Chloro-4-fluoro- 5-(6-morpholin-4- ylthieno[3,2-d}- pyrimidin-4-yl)- phenyl]-(6- methoxy- pyridazin-3-yl)- methanol A B B MS: 488.1/490.1 (M + H.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 8.90 (s, isotopy, rel. peak intensity ratio 1H), 8.00 (d, J = 7.9, 1H), 7.69 (d, J = 9.2, 1H), [%] 100:41) 7.66 (d, J = 10.0, 1H), 7.22 (d, J = 9.1, 1H), 6.61 (d, J = 4.9, 1H), 6.54 (s, 1H), 6.22 (d, J = 4.9, 1H), 3.99 (s, 3H), 3.77-3.73 (m, 4H), 3.44- 3.40 (m, 4H) 129 0 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6- methoxy- pyridazin-3-yl)- methanol (Ena 2) C C B MS: 466.2 (M + H.sup.+); R.sub.t 4.13 min, see racemate (SFC, Chiralpak AS-H, CO.sub.2/ 18% by vol. of methanol, 0.5% by vol. of diethylamine) 130 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6- methoxy- pyridazin-3-yl)- methanol (Ena 1) A A A MS: 466.2 (M + H.sup.+); R.sub.t 2.79 min, see racemate (SFC, Chiralpak AS-H, CO.sub.2/ 18% by vol. of methanol, 0.5% by vol. of diethylamine) 131 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6- methoxy- pyridazin-3-yl)- methanol B B B MS: 466.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 7.83 (t, J = 8.1, 1H), 7.75 (d, J = 9.2, 1H), 7.56 (qd, J = 9.4, 2.8, 2H), 7.45 (t, J = 10.1, 1H), 7.25-7.19 (m, 2H), 6.59-6.57 (m, 1H), 6.20- 6.16 (m, 1H), 4.00 (s, 3H), 3.81-3.75 (m, 4H), 3.48-3.42 (m, 4H) 132 [2-Chloro-5-(2- chloro-7- morpholin-4-yl- quinazolin-4-yl)-4- fluorophenyl]-(6- methoxy- pyridazin-3-yl)- methanol B B A MS: 516.1/518.1/520.0 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 7.94 (d, (Cl.sub.2 isotopy, rel. peak intensity J = 7.7, 1H), 7.72-7.65 (m, 2H), 7.63-7.49 ratio [%] 100:69:12) (m, 2H), 7.21 (d, J = 9.1, 1H), 7.15 (d, J = 2.4, 1H), 6.22 (s, 1H), 4.00 (s, 3H), 3.79-3.73 (m, 4H), 3.53-3.47 (m, 4H) 133 [6-(2-Dimethyl- amino-ethoxy)- pyridazin-3-yl]-[4- fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol C C A MS: 505.3 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 7.69 (d, J = 9.2, 1H), 7.67-7.61 (m, 2H), 7.55-7.47 (m, 2H), 7.44-7.36 (m, 1H), 7.24- 7.15 (m, 2H), 6.49 (d, J = 4.0, 1H), 6.04- 5.98 (m, 1H), 4.56-4.41 (m, 2H), 3.80-3.74 (m, 4H), 3.47-3.41 (m, 4H), 2.64 (t, J = 5.8, 2H), 2.19 (s, 6H) 134 (6-Ethoxy- pyridazin-3-yl)-[4- fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol C B C MS: 462.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 7.68 (d, J = 9.2, 1H), 7.66-7.61 (m, 2H), 7.53-7.50 (m, 2H), 7.43-7.35 (m, 1H), 7.21- 7.19 (m, 1H), 7.17 (d, J = 9.1, 1H), 6.47 (d, J = 4.4, 1H), 6.01 (d, J = 4.3, 1H), 4.52-4.38 (m, 2H), 3.82-3.73 (m, 4H), 3.46-3.41 (m, 4H), 1.36 (t, J = 7.0, 3H) 135 (R)-[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6- methoxy- pyridazin-3-yl)- methanol C D A MS: 482.1/484.1 (M + H.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, isotopy, rel. peak intensity ratio 1H), 7.91 (d, J = 7.7, 1H), 7.69 (d, J = 9.2, 1H), [%] 100:36); R.sub.t 5.34 min (SFC, 7.67 (d, J = 9.5, 1H), 7.62-7.51 (m, 2H), 7.24- Chiralpak AD-H, CO.sub.2/40% by 7.18 (m, 2H), 6.61 (d, J = 4.8, 1H), 6.23 (d, vol. of methanol, 0.5% by vol. of J = 4.8, 1H), 4.00 (s, 3H), 3.81-3.75 (m, 4H), diethylamine) 3.48-3.42 (m, 4H) 136 (S)-[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6- methoxy- pyridazin-3-yl)- methanol A A A MS: 482.1/484.1 (M + H.sup.+) (Cl 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, isotopy, rel. peak intensity ratio 1H), 7.91 (d, J = 7.7, 1H), 7.69 (d, J = 9.2, 1H), [%] 100:36); R.sub.t 3.38 min (SFC, 7.66 (d, J = 9.5, 1H), 7.61-7.52 (m, 2H), 7.24- Chiralpak AD-H, CO.sub.2/40% by 7.19 (m, 2H), 6.61 (d, J = 5.0, 1H), 6.23 (d, vol. of methanol, 0.5% by vol. of J = 4.9, 1H), 4.00 (s, 3H), 3.81-3.75 m, 4H), diethylamine) 3.48-3.43 (m, 4H) 137 [2-Chloro-4-fluoro- 5-(7-morpholin-4- ylquinazolin-4-yl)- phenyl]-(6- methoxy- pyridazin-3-yl)- methanol A B C MS: 482.1/484.1 (M + H.sup.+) (Cl 1H NMR (400 MHz, DMSO-d6) ppm = 9.12 (s, isotopy, rel. peak intensity ratio 1H), 7.91 (d, J = 7.7, 1H), 7.69 (d, J = 9.1, 1H), [%] 100:36) 7.66 (d, J = 9.5, 1H), 7.62-7.51 (m, 2H), 7.24- 7.17 (m, 2H), 6.60 (d, J = 4.9, 1H), 6.23 (d, J = 3.5, 1H), 4.00 (s, 3H), 3.82-3.74 (m, 4H), 3.49-3.42 (m, 4H)

Example 138

1-[5-(7-Morpholin-4-ylquinazolin-4-yl)pyridin-3-yl]-1-thiazol-2-ylethanol (EXAMPLE 138)

(115) ##STR00169##

(116) Thiazole (143 l, 2.0 mmol) in dry tetrahydrofuran (10 ml) was initially introduced in a three-necked flask which had been dried by heating. The reaction solution was cooled to ()78 C. by means of acetone/dry-ice bath. n-Butyllithium (15% solution in n-hexane, 1.63 ml, 2.6 mmol) was added dropwise over a period of 10 min at constant temperature. The reaction mixture was stirred for a further 10 min. The suspension was was subsequently warmed to ()30 C. and re-cooled to ()55 C., and 1-(5-bromopyridin-3-yl)ethanone (380 mg, 1.90 mmol), dissolved in dry tetrahydrofuran (6 ml), was added dropwise at ()40 C. The reaction temperature is allowed to rise to ()10 C. over 1.5 h. After termination of the reaction (HPLC check), saturated ammonium chloride solution was added, and the mixture was stirred at room temperature for 30 min. The reaction mixture was added to a two-phase solution of water (60 ml) and ethyl acetate (80 ml) and extracted three times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated in a rotary evaporator. The oily crude product was purified by means of flash column chromatography (solvent: dichloromethane/2.0% by vol. of methanol, then dichloromethane/3.0% by vol. of methanol+1.0% by vol. of ammonia, amount of flash silica gel 30 g). The product fractions were combined, and the solvents were removed in vacuo in a rotary evaporator, giving 1-(5-bromopyridin-3-yl)-1-thiazol-2-ylethanol (479 mg, 1.68 mmol, MS: 285.0/287.0 [M+H.sup.+], 84% yield) as oil.

(117) ##STR00170##

(118) 1-(5-Bromopyridin-3-yl)-1-thiazol-2-ylethanol (162 mg, 0.55 mmol), bis(pinacolato)diboron (140 mg, 0.55 mmol), 1,1-bis(diphenylphosphino)ferrocene (Dppf, 7.1 mg, 0.013 mmol), 1,1-bis(diphenylphosphino)ferrocenepalladium(II) dichloride [Pd(dppf)Cl.sub.2, 10.4 mg, 0.013 mmol] and potassium acetate (167 mg, 1.7 mmol) were suspended in dry, oxygen-free 1,4-dioxane in a glass vessel with stirrer bar. The glass vessel was sealed using a septum. The reaction solution was stirred and heated at 115 C. for 2.5 h. The reaction monitoring is carried out by means of HPLC. 4-Chloro-7-morpholin-4-ylquinazoline (106 mg, 0.43 mmol), bis(tricyclohexylphosphine)palladium(II) dichloride (9.4 mg, 0.013 mmol) and 2.0 M sodium carbonate solution (531 l) were added to the reaction solution. The reaction mixture was subsequently stirred at a temperature of 125 C. for 1.5 h. The mixture was decanted into water/dichloromethane (1:1 parts by volume, 40 ml), and the resultant solution was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate, filtered and evaporated in a rotary evaporator. The residue was purified by means of flash chromatography [gradient: dichloromethane/20-58% by vol. of a solvent mixture of dichloromethane/methanol 9:1 (parts by volume), CombiFlash Rf 200]. The suitable product fractions were combined, and the solvents were removed in a rotary evaporator, giving 1-[5-(7-morpholin-4-ylquinazolin-4-yl)pyridin-3-yl]-1-thiazol-2-ylethanol (EXAMPLE 138, 95 mg, 0.23 mmol, MS: 420.2 [M+H.sup.+], 53% yield) as oil.

Example 139

{3-[7-(3,6-Dihydro-2H-pyran-4-yl)quinazolin-4-yl]-4-fluorophenyl}thiazol-2-ylmethanol (139)

(119) ##STR00171##

(120) 4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydro-2H-pyran (575 mg, 2.74 mmol), methyl 2-amino-4-bromobenzoate (600 mg, 2.61 mmol), bis(tricyclohexylphosphine)palladium(II) dichloride (57.8 mg, 0.078 mmol) and oxygen-free 2.0 M sodium carbonate solution (3.26 ml, 6.52 mmol) in degassed, oxygen-free 1,4-dioxane (12 ml) were initially introduced in a microwave glass vessel with stirrer bar. The substance mixture was heated at 135 C. for a period of 55 min in a Personal Chemistry Microwave Synthesiser at 100 watts. The reaction solution was subsequently decanted off into a mixture of water (40 ml) and ethyl acetate (30 ml) mixture. The resultant solution was extracted three times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated in vacuo in a rotary evaporator. The residue was purified by means of flash chromatography [gradient: dichloromethane/0-10% by vol. of a solvent mixture of dichloromethane/methanol 10:1 (parts by volume), CombiFlash Rf 200]. The suitable product fractions were combined, and the solvents were removed in a rotary evaporator, giving methyl 2-amino-4-(3,6-dihydro-2H-pyran-4-yl)benzoate (371.1 mg, 1.59 mmol, MS: 234.2 [M+H.sup.+], 61% yield) as solid

(121) ##STR00172##

(122) Methyl 2-amino-4-(3,6-dihydro-2H-pyran-4-yl)benzoate (620 mg, 2.66 mmol), trimethyl orthoformate (564.1 mg, 5.32 mmol) and ammonium acetate (410 mg, 5.32 mmol) dissolved in methanol (20 ml) was initially introduced in a glass vessel with stirrer bar. The substance mixture was stirred overnight at 80 C. Water (10 ml) was subsequently added, and the solid which precipitated out was filtered off with suction, washed with a little water and subsequently dried in vacuo, giving 7-(3,6-dihydro-2H-pyran-4-yl)-3H-quinazolin-4-one (520 mg, 2.28 mmol, MS: 229.1 [M+H.sup.+], 86% yield) as solid.

(123) ##STR00173##

(124) {3-[7-(3,6-Dihydro-2H-pyran-4-yl)quinazolin-4-yl]-4-fluorophenyl}thiazol-2-ylmethanol (EXAMPLE 139) was obtained analogously to the synthetic processes for the preparation of 1-[5-(7-morpholin-4-ylquinazolin-4-yl)pyridin-3-yl]-1-thiazol-2-ylethanol (EXAMPLE 138).

Example 140

[4-Fluoro-3-(7-morpholin-4-ylpyrido[4,3-d]pyrimidin-4-yl)phenyl]thiazol-2-ylmethanol (140)

(125) ##STR00174##

(126) Ethyl 4-amino-6-chloronicotinate (8.38 g, 39.7 mmol) were dissolved in morpholine (40 ml). The substance mixture was heated at 120 C. for 4 h. When the reaction was terminated, the cooled reaction solution was decanted into water (400 ml). The aqueous suspension was stirred for 10 min, and the precipitate was subsequently filtered off. The filter cake was rinsed with a little water and dried overnight at 60 C. in vacuo, giving pure ethyl 4-amino-6-morpholin-4-ylnicotinate (8.55 g, 34.03 mmol, MS: 252.2 [M+H.sup.+], 85% yield) as colourless solid.

(127) ##STR00175##

(128) Analogously to the synthetic process described for EXAMPLE 139, ethyl 4-amino-6-morpholin-4-ylnicotinate (3.54 g, 14.1 mmol) gave 7-morpholin-4-yl-3H-pyrido[4,3-d}pyrimidin-4-one (2.29 g, 9.86 mmol, MS: 233.1 [M+H.sup.+] 70% yield) as solid.

(129) ##STR00176##

(130) 7-Morpholin-4-yl-3H-pyrido[4,3-d}pyrimidin-4-one (600 mg, 2.58 mmol) was suspended in 1,4-dioxane (10 ml). Phosphoryl chloride (POCl.sub.3, 546 l, 5.9 mmol) and Hnig's base (N-ethyldiisopropylamine, 220 l, 1.29 mmol) were added to the reaction mixture. The mixture was subsequently stirred at a temperature of 100 C. for 3 h. After termination of the reaction, the reaction solution was decanted into a semi-saturated sodium hydrogencarbonate solution (80 ml). The aqueous phase was extracted three times with dichloromethane (40 ml in each case). The combined organic phases were dried over sodium sulfate, filtered and evaporated in vacuo in a rotary evaporator, giving 4-chloro-7-morpholin-4-ylpyrido[4,3-d}pyrimidine (627 mg, 2.50 mmol, MS: 251.0/253.0 [M+H.sup.+], 96% yield) as solid.

(131) ##STR00177##

(132) [4-Fluoro-3-(7-morpholin-4-ylpyrido[4,3-d}pyrimidin-4-yl)phenyl]thiazol-2-ylmethanol (EXAMPLE 140) was obtained analogously to the synthetic processes for the preparation of 1-[5-(7-morpholin-4-ylquinazolin-4-yl)pyridin-3-yl]-1-thiazol-2-ylethanol (EXAMPLE 138).

Example 141

[2-Chloro-4-fluoro-5-(7-morpholin-4-ylpyrido[4,3-d}pyrimidin-4-yl)phenyl]-(4-hydroxymethylthiazol-2-yl)methanol (141)

(133) ##STR00178##

(134) 4-(tert-Butyldimethylsilanyloxymethyl)thiazole (10.15 g, 43.5 mmol) dissolved in dry tetrahydrofuran (78 ml) was initially introduced in a two-necked flask with stirrer bar, internal thermometer and septum under argon. The reaction solution was cooled to ()75 C. by means of an acetone/dry-ice bath. n-Butyllithium (15% solution in n-hexane, 29.3 ml, 46.6 mmol) was subsequently slowly added dropwise to the reaction solution at constant temperature. The reaction solution was stirred at ()75 C. for a further 30 min, subsequently warmed to 0 C. Then re-cooled to ()50 C. A solution, pre-cooled to ()50 C., of 5-bromo-2-chloro-4-fluoro-N-methoxy-N-methylbenzamide (5.58 g, 12.4 mmol), dissolved in dry tetrahydrofuran (21 ml), was slowly added dropwise to the reaction solution at ()50 C. over a period of 1.5 h. The reaction solution was stirred at ()50 C. for a further 30 min. When the reaction was complete, water (20 ml) was added to the reaction solution. The reaction solution was then allowed to warm to room temperature with stirring. The reaction solution was diluted with ethyl acetate (400 ml) and saturated sodium chloride solution (100 ml). The phases were separated, and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and evaporated in vacuo in a rotary evaporator. The residue was purified by means of flash chromatography (gradient: cyclohexane/0-7% by vol. of ethyl acetate, CombiFlash Rf 200). The suitable product fractions were combined, and the organic solvents were removed in a rotary evaporator, giving (5-bromo-2-chloro-4-fluorophenyl)-[4-(tert-butyldimethylsilanyloxymethyl)thiazol-2-yl]methanone (4.94 g, 10.39 mmol, MS: main peak 466 [M+H.sup.+], 84% yield) as oil.

(135) ##STR00179##

(136) [4-[[tert-Butyl(dimethyl)silyl]oxymethyl]thiazol-2-yl]-[2-chloro-4-fluoro-5-(7-morpholinopyrido-[4,3-d}pyrimidin-4-yl)phenyl]methanol was prepared analogously to the synthetic processes of EXAMPLES 1 and 2 and 138 from (5-bromo-2-chloro-4-fluorophenyl)-[4-(tert-butyldimethylsilanyloxymethyl)thiazol-2-yl]methanone and 4-chloro-7-morpholin-4-ylpyrido[4,3-d}-pyrimidine.

(137) ##STR00180##

(138) [4-(tert-Butyldimethylsilanyloxymethyl)thiazol-2-yl]-[2-chloro-4-fluoro-5-(7-morpholin-4-ylpyrido[4,3-d]pyrimidin-4-yl)phenyl]methanol (333 mg, 0.55 mmol) was dissolved in 1,4-dioxane (7 ml). 4.0 M HCl dissolved in 1,4-dioxane (1.38 ml, 5.53 mmol) was added, and the reaction solution was subsequently stirred at room temperature for 30 min. When the reaction was complete, the reaction solution was filtered, and solvents were removed in a rotary evaporator. The residue was purified by means of flash chromatography (gradient: dichloromethane/0-15% by vol. of ethanol, CombiFlash Rf 200). The suitable product fractions were combined, and the solvents were removed in vacuo. The residue was taken up in dichloromethane, extracted with saturated sodium hydrogencarbonate solution, dried over sodium sulfate, filtered, and the filtrate was evaporated to dryness, where [2-chloro-4-fluoro-5-(7-morpholin-4-ylpyrido[4,3-d]pyrimidin-4-yl)phenyl]-(4-hydroxymethylthiazol-2-yl)methanol (EXAMPLE 141, 229 mg, 0.47 mmol, MS: 488.0/490.0 [M+H.sup.+], 85% yield) as solid.

Examples 142 and 143

2-Chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(4-hydroxymethylthiazol-2-yl)methanol (142)

[2-Chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(4-methylaminomethylthiazol-2-yl)methanol (143)

(139) ##STR00181##

(140) [2-Chloro-4-fluoro-5-(7-morpholin-4-ylpyrido[4,3-d]pyrimidin-4-yl)phenyl]-(4-hydroxymethylthiazol-2-yl)methanol (46.6 mg, 96 mop was dissolved in dry tetrahydrofuran (3.1 ml) under argon. N-Ethyldiisopropylamine (98 l, 57.4 mop and methanesulfonyl chloride (14.8 l, 191 mol) were added. The reaction solution was stirred at room temperature for 30 min. Methylamine (40% solution in water, 183 l, 1.91 mol) was subsequently added, and the mixture was stirred at room temperature for a further 2 h. After termination of the reaction, ethyl acetate (15 ml) and saturated sodium chloride solution (10 ml) were added to the reaction solution. The phases were separated, and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered. The filtrate was evaporated in a rotary evaporator, and the residue was purified by means of preparative RP-HPLC (gradient water+0.1% of trifluoroacetic acid/acetonitrile+0.1% of trifluoroacetic acid, Sunfire Prep C-18 150-21 mm, flow rate: 50 ml/min., =220 nm). The suitable product fractions were combined, and the solvents were removed in vacuo in a rotary evaporator, and the residue was freeze-dried from dioxane/water, where [2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(4-methylaminomethylthiazol-2-yl)methanol (EXAMPLE 143, 14.8 mg, 0.030 mmol, MS: 500.1/502.0 [M+H.sup.+], 31% yield) as solid.

Examples 144, 145 and 146

(141) ##STR00182##

(142) Racemic [4-fluoro-3-(6-morpholin-4-ylthieno[3,2-d}pyrimidin-4-yl)phenyl]thiazol-2-ylmethanol (EXAMPLE 144, 35 mg, 0.082 mmol) was separated by chromatography into its enantiomers on a chiral stationary phase using preparative SFC: after analytic column screening for identification of the most suitable chiral phase having the highest selectivity, the Lux amylose-2 phase from Phenomex was selected. SFC conditions: apparatus: SFC Berger minigram; column: Lux amylose-2, 2504.6 mm; eluent: carbon dioxide+20% by vol. of methanol+0.5% by vol. of diethylamine, flow rate: 5 ml/min, wavelength: 220 nm. The preparative separation into the enantiomers was carried out under the same conditions in SFC Berger minigram Stacked Injection Mode. The suitable fractions were collected, and the solvents were removed in vacuo in a rotary evaporator, giving enantiomerically pure [4-fluoro-3-(6-morpholin-4-ylthieno[3,2-d}pyrimidin-4-yl)phenyl]thiazol-2-ylmethanol (EXAMPLE 145, R.sub.t=7.85 min 12 mg, 0.028 mmol, >99% ee Ena 1) and [4-fluoro-3-(6-morpholin-4-ylthieno[3,2-d}pyrimidin-4-yl)phenyl]thiazol-2-ylmethanol (EXAMPLE 146, R.sub.t=8.82 min, 12.0 mg, 0.028 mmol, 92% ee, Ena 2) as solids.

(143) Compounds which were prepared analogously to EXAMPLES 138-146 can be found in Table 5 below.

(144) TABLE-US-00005 TABLE 5 Compounds of the formula (I) IC.sub.50 IC.sub.50 K.sub.i DNA- pDNA- [Kv1.11 No. Structural formula Name PK PK hERG] 138 1-[5-(7-Morpholin-4- ylquinazolin-4-yl)- pyridin-3-yl]-1- thiazol-2-ylethanol D B MS: 420.2 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 8.97 (d, J = 2.2, 1H), 8.83 (d, J = 2.1, 1H), 8.30 (t, J = 2.2, 1H), 7.82 (d, J = 9.5, 1H), 7.79 (d, J = 3.2, 1H), 7.65 (d, J = 3.3, 1H), 7.57 (dd, J = 9.5, 2.6, 1H), 7.22 (d, J = 2.5, 1H), 7.09 (s, 1H), 3.82-3.75 (m, 4H), 3.50-3.43 (m, 4H), 2.02 (s, 3H) 139 {3-[7-(3,6-Dihydro- 2H-pyran-4-yl)- quinazolin-4-yl]-4- fluoro-phenyl}- thiazol-2-ylmethanol C D A MS: 420.0 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.36 (s, 1H), 8.02 (d, J = 1.8, 1H), 7.94 (dd, J = 8.9, 1.9, 1H), 7.76-7.69 (m, 4H), 7.65 (d, J = 3.2, 1H), 7.49-7.43 (m, 1H), 7.00-6.96 (m, 1H), 6.71- 6.67 (m, 1H), 6.11-6.08 (m, 1H), 4.33-4.30 (m, 2H), 3.89 (t, J = 5.5, 2H), 2.65-2.60 (m, 2H) 140 [4-Fluoro-3-(7- morpholin-4-yl- pyrido[4,3-d}- pyrim idin-4-yl)- phenyl]thiazol-2-yl- methanol D D B MS: 424.2 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.16 (s, 1H), 8.80 (d, J = 3.6, 1H), 7.77-7.70 (m, 3H), 7.65 (d, J = 3.2, 1H), 7.48-7.42 (m, 1H, 7.08- 6.94 (m, 2H), 6.10 (s, 1H), 3.78-3.66 (m, 8H) 141 [2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- pyrido[4,3-d}- pyrimidin-4-yl)- phenyl]-(4- hydroxymethyl- thiazol-2-yl)- methanol D D B MS: 488.0/490.0 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.15 (s, (Cl isotopy, rel. peak 1H), 8.84 (d, J = 3.4, 1H), 7.83 (d, J = 7.6, 1H), intensity ratio [%] 100:38) 7.74 (d, J = 9.7, 1H), 7.39-7.35 (m, 1H), 7.04 (s, 1H), 6.99 (s, 1H), 6.28 (s, 1H), 5.24 (s, 1H), 4.50 (s, 2H), 3.77-3.69 (m, 8H) 142 [2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(4- hydroxymethyl- thiazol-2-yl)- methanol A B D MS: 487.1/489.0 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.10 (s, (Cl isotopy, rel. peak 1H), 7.75-7.69 (m, 2H), 7.59-7.49 (m, 2H), intensity ratio [%] 100:41) 7.36 (t, J = 1.1, 1H), 7.23-7.17 (m, 1H), 7.00 (d, J = 5.1, 1H), 6.27 (d, J = 5.0, 1H), 5.24 (t, J = 5.7, 1H), 4.52-4.45 (m, 2H), 3.81-3.74 (m, 4H), 3.49-3.41 (m, 4H) 143 [2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(4- methylaminomethyl- thiazol-2-yl)- methanol C C C MS: 500.1/502.0 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, (Cl isotopy, rel. peak 1H), 8.26 (s, 1H), 7.76-7.69 (m, 2H), 7.58- intensity ratio [%] 100:34) 7.50 (m, 2H), 7.48-7.43 (m, 1H), 7.24-7.16 (m, 1H), 6.97 (s, 1H), 6.28 (s, 1H), 3.80 (s, 2H), 3.79-3.74 (m, 4H), 3.48-3.42 (m, 4H), 2.33 (s, 3H) 144 [4-Fluoro-3-(6- morpholin-4-yl- thieno[3,2-d}- pyrimidin-4-yl)- phenyl]thiazol-2-yl- methanol A B B MS: 429.0 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 8.89 (s, 1H), 7.76 (dd, J = 7.0, 2.3, 1H), 7.73 (d, J = 3.2, 1H), 7.69-7.64 (m, 2H), 7.43-7.38 (m, 1H), 6.96 (d, J = 4.6, 1H), 6.53 (s, 1H), 6.07 (d, J = 4.6, 1H), 3.77-3.71 (m, 4H), 3.44-3.38 (m, 4H) 145 0 [4-Fluoro-3-(6- morpholin-4-yl- thieno[3,2-d}- pyrimidin-4-yl)- phenyl]thiazol-2-yl- methanol (Ena 1) A B A MS: 429.0 (M + H.sup.+); R.sub.t 7.85 see racemate min, (SFC, Lux amylose, CO2/0.5% by vol. of methanol) 146 [4-Fluoro-3-(6- morpholin-4-yl- thieno[3,2-d}- pyrimidin-4-yl)- phenyl]thiazol-2-yl- methanol (Ena 2) A B A MS: 429.0 (M + H.sup.+); R.sub.t 8.82 see racemate min, (SFC, Lux amylose-2, CO2/0.5% by vol. of methanol) 147 [5-(7-Morpholin-4- ylquinazolin-4-yl)- thiophen-2-yl]- thiazol-2-ylmethanol D C MS: 411.0 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 8.93 (s, 1H), 8.34 (d, J = 9.5, 1H), 7.83 (d, J = 3.9, 1H), 7.79 (d, J = 3.2, 1H), 7.71 (d, J = 3.2, 1H), 7.56 (dd, J = 9.5, 2.7, 1H), 7.32 (d, J = 4.8, 1H), 7.26- 7.24 (m, 1H), 7.16 (d, J = 2.6, 1H), 6.31-6.29 (m, 1H), 3.81-3.75 m, 4H), 3.47-3.41 (m, 4H) 148 [3-(7-Morpholin-4- ylquinazolin-4-yl)- phenyl]thiazol-2-yl- methanol C D C MS: 405.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.07 (s, 1H), 7.86 (d, J = 9.4, 1H), 7.83-7.81 (m, 1H), 7.74 (d, J = 3.2, 1H), 7.68-7.64 (m, 3H), 7.59- 7.55 (m, 1H), 7.52 (dd, J = 9.5, 2.6, 1H), 7.20 (d, J = 2.6, 1H), 6.93 (d, J = 4.5, 1H), 6.10 (d, J = 4.0, 1H), 3.80-3.76 (m, 4H), 3.46-3.42 (m, 4H) 149 [3-(7-Morpholin-4- ylquinazolin-4-yl)- phenyl]thiazol-2-yl- methanol (Ena 1) D A MS: 405.2 (M + H.sup.+); R.sub.t see racemate 10.57 min, (HPLC, Chiralpak AD-H, heptane/ethanol 40/60) 150 [3-(7-Morpholin-4- ylquinazolin-4-yl)- phenyl]thiazol-2-yl- methanol (Ena 2) C C A MS: 405.2 (M + H.sup.+); R.sub.t 13.55 see racemate min, (HPLC, Chiralpak AD- H, heptane/ethanol 40/60) 151 1-[5-(7-Morpholin- 4-ylquinazolin-4-yl)- pyridin-3-yl]-1- thiazol-2-ylethanol (Ena 1) D MS: 420.2 (M + H.sup.+); R.sub.t 8.95 see racemate min, (SFC, Chiralpak AS-H, CO2/10% by vol. of methanol, 0.5% by vol. of diethylamine) 152 1-[5-(7-Morpholin- 4-ylquinazolin-4-yl)- pyridin-3-yl]-1- thiazol-2-ylethanol (Ena 2) C D A MS: 420.2 (M + H.sup.+), R.sub.t see racemate 10.45 min, (SFC, Chiralpak AS-H, CO2/10% by vol. of methanol, 0.5% by vol. of diethylamine) 153 1-[4-(7-Morpholin- 4-ylquinazolin-4-yl)- pyridin-2-yl]-1- thiazol-2-ylethanol D MS: 420.2 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 8.73 (dd, J = 5.0, 0.8, 1H), 7.99-7.97 (m, 1H), 7.79 (d, J = 9.4, 1H), 7.72 (d, J = 3.2, 1H), 7.64 (dd, J = 5.0, 1.6, 1H), 7.62 (d, J = 3.2, 1H), 7.56 (dd, J = 9.5, 2.6, 1H), 7.23 (d, J = 2.5, 1H), 6.84 (s, 1H), 3.81-3.75 (m, 4H), 3.49-3.44 (m, 4H), 2.04 (s, 3H) 154 1-[3-(7-Morpholin- 4-ylquinazolin-4-yl)- phenyl]-1-thiazol-2- ylethanol D B MS: 419.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.07 (s, 1H), 7.96-7.93 (m, 1H), 7.83 (d, J = 9.4, 1H), 7.79-7.76 (m, 1H), 7.74 (d, J = 3.2, 1H), 7.63- 7.61 (m, 1H), 7.60 (d, J = 3.3, 1H), 7.55 (d, J = 7.7, 1H), 7.53-7.50 (m, 1H), 7.20 (d, J = 2.6, 1H), 6.82 (s, 1H), 3.81-3.75 (m, 4H), 3.47- 3.42 (m, 4H), 1.98 (s, 3H) 155 00 1-[4-methyl-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-1-thiazol-2- ylethanol D MS: 433.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.07 (s, 1H), 7.70 (d, J = 3.2, 1H), 7.61 (dd, J = 8.0, 2.1, 1H), 7.57 (d, J = 3.2, 1H), 7.48-7.44 (m, 2H), 7.34 (d, J = 8.1, 1H), 7.32 (d, J = 9.3, 1H), 7.19 (d, J = 2.5, 1H), 6.70 (s, 1H), 3.79-3.76 (m, 4H), 3.44-3.41 (m, 4H), 2.03 (s, 3H), 1.92 (s, 3H) 156 01 1-[4-(7-Morpholin- 4-ylquinazolin-4-yl)- thiophen-2-yl]-1- thiazol-2-ylethanol D MS: 425.0 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 8.99 (s, 1H), 8.13 (d, J = 9.5, 1H), 8.04 (d, J = 1.5, 1H), 7.76 (d, J = 3.2, 1H), 7.64 (d, J = 3.2, 1H), 7.54 (dd, J = 9.5, 2.6, 1H), 7.52 (d, J = 1.5, 1H), 7.20 (s, 1H), 7.16 (d, J = 2.6, 1H), 3.82-3.75 (m, 4H), 3.47-3.40 (m, 4H), 2.04 (s, 3H) 157 02 1-[4-(7-Morpholin- 4-ylquinazolin-4-yl)- pyridin-2-yl]-1- thiazol-2-ylethanol (Ena 1) D MS: 420.2 (M + H.sup.+); R.sub.t see racemate 22.14 min, (HPLC, Chiralpak AD-H, heptane/ethanol 70/30, 0.5% by vol. of diethylamine) 158 03 1-[4-(7-Morpholin- 4-ylquinazolin-4-yl)- pyridin-2-yl]-1- thiazol-2-ylethanol (Ena 2) D MS: 420.2 (M + H.sup.+); R.sub.t see racemate 27.88 min, (HPLC, Chiralpak AD-H, heptane/ethanol 70/30, 0.5% by vol. of diethylamine) 159 04 2,2,2-Trifluoro-1-[3- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-1-thiazol-2- ylethanol C D D MS: 473.0 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, 1H), 8.54 (s, 1H), 8.15-8.13 (m, 1H), 7.98- 7.95 (m, 1H), 7.94 (d, J = 3.3, 1H), 7.87 (d, J = 3.2, 1H), 7.83-7.79 (m, 2H), 7.67 (t, J = 7.8, 1H), 7.53 (dd, J = 9.5, 2.6, 1H), 7.21 (d J = 2.6, 1H), 3.80-3.76 (m, 4H), 3.47-3.43 (m, 4H) 160 05 [5-(7-Morpholin-4- ylquinazolin-4-yl)- thiophen-2-yl]- thiazol-2-yl- methanol (Ena 1) D MS: 409.0 (M H.sup.+); see racemate O-TBDPS ether derivative: R.sub.t 4.78 min (SFC, Chiralpak AD-H, CO.sub.2/30% by vol. of 2-propanol, 0.5% by vol. of diethylamine 161 06 [5-(7-Morpholin-4- ylquinazolin-4-yl)- thiophen-2-yl]- thiazol-2-yl- methanol (Ena 2) D MS: 409.0 (M H.sup.+); see racemate O-TBDPS ether derivative: R.sub.t 7.20 min (SFC, Chiralpak AD-H, CO.sub.2/30% by vol. of 2-propanol, 0.5% by vol. of diethylamine 162 07 1-[2-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-1-thiazol-2- ylethanol D MS: 437.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.07 (s, 1H), 7.94-7.87 (m, 1H), 7.71 (d, J = 3.2, 1H), 7.63 (d, J = 3.3, 1H), 7.55-7.40 (m, 4H), 7.17 (d, J = 2.4, 1H), 6.75 (s, 1H), 3.79-3.74 (m, 4H), 3.46-3.40 (m, 4H), 2.01 (s, 3H) 163 08 1-[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-1-thiazol-2- ylethanol C D C MS: 437.2 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 7.82-7.75 (m, 2H), 7.73 (d, J = 3.2, 1H), 7.61 (d, J = 3.2, 1H), 7.53-7.50 (m, 2H), 7.41- 7.36 (m, 1H), 7.20 (d, J = 1.9, 1H), 6.90 (s, 1H), 3.80-3.75 (m, 4H), 3.46-3.41 (m, 4H), 1.95 (s, 3H) 164 09 [5-(7-Morpholin-4- ylquinazolin-4-yl)- thiophen-3-yl]- thiazol-2-yl- methanol D MS: 411.0 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 8.95 (s, 1H), 8.30 (d, J = 9.5, 1H), 7.93 (d, J = 1.3, 1H), 7.80-7.78 (m, 1H), 7.76 (d, J = 3.2, 1H), 7.67 (d, J = 3.2, 1H), 7.62 (dd, J = 9.5, 2.7, 1H), 7.17 (d, J = 2.6, 1H), 6.93 (d, J = 5.0, 1H), 6.14-6.11 (m, 1H), 3.81-3.76 (m, 4H), 3.48-3.43 (m, 4H) 165 0 1-[4-(7-Morpholin- 4-ylquinazolin-4-yl)- thiophen-2-yl]-1- thiazol-2-ylethanol (Ena 1) D MS: 425.0 (M + H.sup.+); R.sub.t 1H NMR (500 MHz, DMSO-d6) ppm = 8.99 (s, 5.32 min, (SFC, Chiralcel 1H), 8.13 (d, J = 9.4, 1H), 8.05 (d, J = 1.5, 1H), OJ-H, CO2/25% by vol. of 7.76 (d, J = 3.2, 1H), 7.64 (d, J = 3.2, 1H), 7.54 2-propanol, 0.5% by vol. of (dd, J = 9.5, 2.6, 1H), 7.52 (d, J = 1.5, 1H), 7.20 diethylamine) (s, 1H), 7.16 (d, J = 2.6, 1H), 3.81-3.74 (m, 4H), 3.46-3.39 (m, 4H), 2.04 (s, 3H) 166 1-[4-(7-Morpholin- 4-ylquinazolin-4-yl)- thiophen-2-yl]-1- thiazol-2-ylethanol (Ena 2) D MS: 425.0 (M + H.sup.+); R.sub.t 1H NMR (500 MHz, DMSO-d6) ppm = 8.99 (s, 7.18 min, (SFC, Chiralcel 1H), 8.13 (d, J = 9.4, 1H), 8.05 (d, J = 1.5, 1H), OJ-H, CO2/25% by vol. of 7.76 (d, J = 3.2, 1H), 7.64 (d, J = 3.2, 1H), 7.54 2-propanol, 0.5% by vol. of (dd, J = 9.5, 2.7, 1H), 7.52 (d, J = 1.5, 1H), 7.20 diethylamine) (s, 1H), 7.16 (d, J = 2.6, 1H), 3.81-3.75 (m, 4H), 3.46-3.40 (m, 4H), 2.03 (s, 3H) 167 [5-(7-Morpholin-4- ylquinazolin-4-yl)- thiophen-3-yl]- thiazol-2-yl- methanol (Ena 1) D MS: 411.0 (M + H.sup.+); 1H NMR (500 MHz, DMSO-d6) ppm = 8.95 (s, O-TBDPS-Etherderivat: R.sub.t 1H), 8.30 (d, J = 9.5, 1H), 7.94-7.92 (m, 1H), 13.11 min (SFC, Chiralpak 7.79-7.78 (m, 1H), 7.76 (d, J = 3.2, 1H), 7.67 IA, CO.sub.2/20% by vol. of (d, J = 3.2, 1H), 7.62 (dd, J = 9.5, 2.7, 1H), 7.17 2-methanol, 0.5% by vol. of (d, J = 2.6, 1H), 6.93 (d, J = 5.0, 1H), 6.12 (d, diethylamine J = 4.9, 1H), 3.81-3.77 (m, 4H), 3.47-3.44 (m, 4H) 168 [5-(7-Morpholin-4- ylquinazolin-4-yl)- thiophen-3-yl]- thiazol-2-yl- methanol (Ena 2) D MS: 411.0 (M + H.sup.+); 1H NMR (500 MHz, DMSO-d6) ppm = 8.95 (s, O-TBDPS ether derivative: 1H), 8.30 (d, J = 9.5, 1H), 7.94-7.92 (m, 1H), R.sub.t 16.82 min (SFC, 7.79-7.78 (m, 1H), 7.76 (d, J = 3.2, 1H), 7.67 Chiralpak IA, CO.sub.2/20% by (d, J = 3.2, 1H), 7.62 (dd, J = 9.5, 2.7, 1H), 7.17 vol. of 2-methanol, 0.5% by (d, J = 2.6, 1H), 6.93 (s, 1H), 6.12 (s, 1H), 3.82- vol. of diethylamine 3.74 (m, 4H), 3.50-3.42 (m, 4H) 169 [3-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thiazol-2-yl- methanol C D MS: 423.0 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, 1H), 7.86 (d, J = 9.4, 1H), 7.77 (d, J = 3.2, 1H), 7.68-7.66 (m, 2H), 7.54 (dd, J = 9.4, 2.6, 1H), 7.51-7.46 (m, 2H), 7.21 (d, J = 2.6, 1H), 7.08 (d, J = 4.7, 1H), 6.14 (d, J = 4.7, 1H), 3.80-3.76 (m, 4H), 3.47-3.43 (m, 4H) 170 [2-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thiazol-2-yl- methanol C C MS: 423.0 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.04 (s, 1H), 7.85-7.81 (m, 2H), 7.77-7.73 (m, 1H), 7.72 (d, J = 3.2, 1H), 7.66 (d, J = 3.2, 1H), 7.52 (dd, J = 9.5, 2.6, 1H), 7.44-7.39 (m, 1H), 7.18 (d, J = 2.5, 1H), 7.05 (d, J = 4.9, 1H), 6.28 (d, J = 3.8, 1H), 3.79-3.75 (m, 4H), 3.33-3.29 (m, 4H) 171 [3,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thiazol-2-yl- methanol A B D MS: 441.0 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 7.75 (d, J = 3.2, 1H), 7.72-7.66 (m, 2H), 7.61-7.57 (m, 1H), 7.56-7.49 (m, 2H), 7.21 (d, J = 2.4, 1H), 7.10 (d, J = 4.8, 1H), 6.10 (d, J = 4.8, 1H), 3.81-3.75 (m, 4H), 3.48-3.43 (m, 4H) 172 2,2,2-Trifluoro-1-[3- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-1-thiazol-2- ylethanol (Ena 1) C D MS: 473.0 (M + H.sup.+); R.sub.t see racemate 12.21 min, (HPLC, Chiralpak AD-H, n-heptane/ethanol, 70:30, vol.:vol) 173 2,2,2-Trifluoro-1-[3- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-1-thiazol-2- ylethanol (Ena 2) A C D MS: 473.0 (M + H.sup.+); R.sub.t see racemate 16.91 min, (HPLC, Chiralpak AD-H, n-heptane/ethanol, 70:30, vol.:vol.) 174 7-Morpholin-4-yl-4- piperidin-1-yl- thieno[3,2-d}- pyrimidine C D MS: 305.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 8.88-8.85 (m, 2H), 8.19-8.17 (m, 1H), 7.84 (d, J = 9.4, 1H), 7.78 (d, J = 3.2, 1H), 7.69 (d, J = 3.2, 1H), 7.56 (dd, J = 9.5, 2.6, 1H), 7.22 (d, J = 2.6, 1H), 7.14 (d, J = 4.8, 1H), 6.23 (d, J = 4.8, 1H), 3.81-3.76 (m, 4H), 3.48-3.43 (m, 4H) 175 0 4-[2-Fluoro-5- (methoxy-thiazol-2- ylmethyl)phenyl]-7- morpholin-4-yl- quinazoline D MS: 337.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 7.78 (d, J = 3.2, 1H), 7.73 (d, J = 3.2, 1H), 7.67-7.62 (m, 2H), 7.54-7.52 (m, 2H), 7.49- 7.44 (m, 1H), 7.21-7.19 (m, 1H), 5.84 (s, 1H), 3.80-3.75 (m, 4H), 3.46-3.43 (m, 4H), 3.43 (s, 3H) 176 4-[2-Fluoro-5-(- methoxy-thiazol-2- ylmethyl)phenyl]-7- morpholin-4-yl- quinazoline (Ena 1) C MS: 437.2 (M + H.sup.+); R.sub.t 8.47 see racemate min, (SFC, Chiralcel OD-H, CO2/20% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 177 4-[2-Fluoro-5-(- methoxythiazol-2- ylmethyl)phenyl]-7- morpholin-4-yl- quinazoline (Ena 2) B D A MS: 437.2 (M + H.sup.+); R.sub.t 9.90 see racemate min, (SFC, Chiralcel OD-H, CO2/20% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 178 [3,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thiazol-2-yl- methanol (Ena 1) A B A MS: 441.0 (M + H.sup.+); R.sub.t 8.34 see racemate min, (SFC, Chiralcel OD-H, CO2/20% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 179 [3,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thiazol-2-yl- methanol (Ena 2) B B D MS: 441.0 (M + H.sup.+); R.sub.t 9.68 see racemate min, (SFC, Chiralcel OD-H, CO2/20% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 180 [6-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- pyridin-3-yl]thiazol- 2-ylmethanol A C D MS: 424.2 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 8.56-8.52 (m, 1H), 8.21 (dd, J = 9.0, 2.3, 1H), 7.77 (d, J = 3.2, 1H), 7.69 (d, J = 3.2, 1H), 7.59-7.52 (m, 2H), 7.23-7.20 (m, 1H), 7.18 (d, J = 4.7, 1H), 6.23 (d, J = 4.5, 1H), 3.82-3.73 (m, 4H), 3.50-3.42 (m, 4H) 181 [2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(4-methyl- thiazol-2-yl)- methanol A B D MS: 471.1/473.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, (Cl isotopy, rel. peak 1H), 7.73 (dd, J = 10.5, 8.6, 2H), 7.57-7.51 (m, intensity ratio [%] 100:42) 2H), 7.22-7.18 (m, 2H), 6.97 (s, 1H), 6.26 (s, 1H), 3.80-3.74 (m, 4H), 3.49-3.41 (m, 4H), 2.30 (d, J = 1.0, 3H) 182 [3-(6-Morpholin-4- ylthieno[3,2-d}- pyrimidin-4-yl)- phenyl]thiazol-2-yl- methanol C C MS: 411.0 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 8.90 (s, 1H), 8.14 (t, J = 1.8, 1H), 7.97-7.93 (m, 1H), 7.73 (d, J = 3.2, 1H), 7.68-7.64 (m, 2H), 7.61- 7.54 (m, 1H), 6.93 (d, J = 4.4, 1H), 6.54 (s, 1H), 6.09 (d, J = 4.4, 1H), 3.81-3.74 (m, 4H), 3.47- 3.41 (m, 4H) 183 [5-(7-Morpholin-4- ylquinazolin-4-yl)- pyridin-3-yl]thiazol- 2-ylmethanol (Ena 1) C MS: 406.0 (M + H.sup.+); R.sub.t see racemate 20.67 min, (HPLC, Chiralcel OD-H, 2-propanol) 184 [5-(7-Morpholin-4- ylquinazolin-4-yl)- pyridin-3-yl]thiazol- 2-ylmethanol (Ena 2) C MS: 406.0 (M + H.sup.+); Rt see racemate 24.19 min, (HPLC, Chiralcel OD-H, 2-propanol) 185 0 (S)-[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(4- hydroxymethyl- thiazol-2-yl)- methanol A B A MS: 487.1/489.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, (Cl isotopy, rel. peak 1H), 7.73 (dd, J = 8.6, 4.8, 2H), 7.58-7.50 (m, intensity ratio [%] 100:41); 2H), 7.39-7.34 (m, 1H), 7.22-7.18 (m, 1H), R.sub.t 2.83 min (SFC, Chiralpak 7.02 (d, J = 5.0, 1H), 6.27 (d, J = 5.0, 1H), 5.27 AD-H, CO.sub.2/40% by vol. of (t, J = 5.7, 1H), 4.51-4.47 (m, 2H), 3.80-3.74 methanol, 0.5% by vol. of (m, 4H), 3.48-3.40 m, 4H) diethylamine) 186 (R)-[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(4- hydroxymethyl- thiazol-2-yl)- methanol C C D MS: 487.1/489.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, (Cl isotopy, rel. peak 1H), 7.73 (dd, J = 8.6, 4.5, 2H), 7.57-7.52 (m, intensity ratio [%] 100:41); 2H), 7.38-7.35 (m, 1H), 7.22-7.19 (m, 1H), R.sub.t 5.77 min (SFC, Chiralpak 7.03 (d, J = 5.0, 1H), 6.27 (d, J = 5.0, 1H), 5.27 AD-H, CO.sub.2/40% by vol. of (t, J = 5.7, 1H), 4.50-4.46 (m, 2H), 3.80-3.74 methanol, 0.5% by vol. of (m, 4H), 3.48-3.42 (m, 4H) diethylamine) 187 {2-Chloro-4-fluoro- 5-[7-(3-oxa-8-aza- bicyclo[3.2.1]oct-8- yl)quinazolin-4-yl]- phenyl}-(4-hydroxy- methylthiazol-2-yl)- methanol D D B MS: 513.1/515.0 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.03 (s, (Cl isotopy, rel. peak 1H), 7.71 (t, J = 8.5, 2H), 7.50 (dd, J = 9.3, 3.2, intensity ratio [%] 100:41) 1H), 7.40 (dd, J = 9.4, 2.5, 1H), 7.37-7.35 (m, 1H), 7.13 (d, J = 2.4, 1H), 7.01 (d, J = 5.1, 1H), 6.27 (d, J = 5.0, 1H), 5.26 (t, J = 5.7, 1H), 4.52- 4.50 (m, 2H), 4.50-4.47 (m, 2H), 3.69 (d, J = 10.9, 2H), 3.57-3.50 (m, 2H), 2.09-1.94 (m, 4H) 188 [6-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- pyridin-3-yl]thiazol- 2-ylmethanol (Ena 1) A C A MS: 424.0 (M + H.sup.+); R.sub.t 44.51 see racemate min, (HPLC, Chiralcel OD- H, hexane/2-propanol 80/20) 189 [6-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- pyridin-3-yl]thiazol- 2-ylmethanol (Ena 2) B B B MS: 424.0 (M + H.sup.+); R.sub.t 49.66 see racemate min, (HPLC, Chiralcel OD- H, hexane/2-propanol 80/20) 190 [2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(4-ethyl- aminomethyl- thiazol-2-yl)- methanol C B B MS: 514.2/516.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, (Cl isotopy, rel. peak 1H), 8.25 (s, 1H), 7.73 (d, J = 1.6, 1H), 7.71 (s, intensity ratio [%] 100:41) 1H), 7.58-7.49 (m, 2H), 7.44-7.40 (m, 1H), 7.23-7.18 (m, 1H), 7.05 (s, 1H), 6.27 (s, 1H), 3.80-3.76 (m, 6H), 3.48-3.40 (m, 4H), 2.60 (q, J = 7.1, 2H), 1.01 (t, J = 7.1, 3H) 190 (4-Aminomethyl- thiazol-2-yl)-[2- chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol C B B MS: 486.0/488.1 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.09 (s, (Cl isotopy, rel. peak 1H), 8.30 (s, 1H), 7.76-7.69 (m, 2H), 7.57- intensity ratio [%] 100:38) 7.50 (m, 2H), 7.48-7.43 (m, 1H), 7.23-7.17 (m, 1H), 6.28 (s, 1H), 3.86 (s, 2H), 3.81-3.74 (m, 4H), 3.47-3.44 (m, 4H) 191 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(1-methyl- 1H-pyrazol-4-yl)- methanol A D A MS: 420.1 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 7.68-7.33 (m, 6H), 7.31-7.15 (m, 2H), 5.76 (s, 2H), 3.90-3.64 (m, 7H), 3.51-3.39 (m, 4H) 192 (4,5-Dimethyl- thiazol-2-yl)-[2- fluoro-5-(7- morpholin-4-yl- pyrido[4,3-d}- pyrimidin-4-yl)- pyridin-3-yl]- methanol D C MS: 453.0 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.14 (s, 1H), 9.09 (s, 1H), 8.67-8.65 (m, 1H), 8.46 (dd, J = 9.0, 2.4, 1H), 7.03-6.99 (m, 2H), 6.11 (d, J = 5.2, 1H), 3.77-3.68 (m, 8H), 2.31 (s, 3H), 2.19 (s, 3H) 194 (4,5-Dimethyl- thiazol-2-yl)-[2- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- pyridin-3-yl]- methanol C A MS: 452.2 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 8.58-8.56 (m, 1H), 8.37 (dd, J = 9.0, 2.4, 1H), 7.87 (d, J = 9.4, 1H), 7.57 (dd, J = 9.4, 2.6, 1H), 7.22 (d, J = 2.5, 1H), 6.99 (d, J = 5.1, 1H), 6.11 (d, J = 5.1, 1H), 3.80-3.76 (m, 4H), 3.49- 3.43 (m, 4H), 2.30 (s, 3H), 2 19 (s, 3H) 195 0 [6-Fluoro-5-(7- morpholin-4-yl- pyrido[4,3-d}- pyrimidin-4-yl)- pyridin-3-yl]-(4- methyl-thiazol-2-yl)- methanol D B MS: 439.0 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.17 (s, 1H), 8.90 (d, J = 2.5, 1H), 8.57-8.53 (m, 1H), 8.29 (dd, J = 9.1, 2.4, 1H), 7.24-7.21 (m, 1H), 7.10 (d, J = 4.9, 1H), 7.00 (s, 1H), 6.16 (d, J = 4.9, 1H), 3.79-3.67 (m, 8H), 2.33 (d, J = 1.0, 3H) 196 (4,5-Dimethyl- thiazol-2-yl)-[6- fluoro-5-(7- morpholin-4-yl- pyrido[4,3-d}- pyrimidin-4-yl)- pyridin-3-yl]- methanol C D A MS: 407.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.16 (s, 1H), 8.90 (d, J = 2.4, 1H), 8.53 (d, J = 2.3, 1H), 8.27 (dd, J = 9.1, 2.4, 1H), 7.06 (d, J = 4.9, 1H), 6.99 (s, 1H), 6.08 (d J = 4.9, 1H), 3.76-3.69 (m, 8H), 2.30 (s, 3H), 2.21 (s, 3H) 197 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(1- isopropyl-1H- pyrazol-4-yl)- methanol B C D MS: 448.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 7.64-7.60 (m, 1H), 7.60-7.57 (m, 2H), 7.56-7.50 (m, 2H), 7.41-7.35 (m, 1H), 7.28 (s, 1H), 7.20 (d, J = 2.2, 1H), 5.76 (s, 2H), 4.42 (h, J = 6.6, 1H), 3.80-3.76 (m, 4H), 3.46-3.42 (m, 4H), 1.36 (d, J = 6.7, 6H) 198 (1-tert-Butyl-1H- pyrazol-4-yl)-[2- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- pyridin-3-yl]- methanol C A MS: 463.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 8.54-8.49 (m, 1H), 8.46 (dd, J = 9.4, 2.6, 1H), 7.89 (d, J = 9.4, 1H), 7.73 (s, 1H), 7.57 (dd, J = 9.5, 2.6, 1H), 7.36 (s, 1H), 7.23 (d, J = 2.5, 1H), 6.02 (d, J = 4.8, 1H), 5.95 (d, J = 4.6, 1H), 3.82-3.75 (m, 4H), 3.50-3.42 (m, 4H), 1.48 (s, 9H) 199 4-[5-(Difluoro- methoxy-thiazol-2- ylmethyl)-2-fluoro- phenyl]-7- morpholin-4-yl- quinazoline B D D MS: 473.0 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 7.85 (d, J = 3.2, 1H), 7.81 (d, J = 3.2, 1H), 7.73-7.71 (m, 2H), 7.55-7.52 (m, 2H), 7.52- 7.48 (m, 1H), 7.22-6.82 (m, 3H), 3.80-3.75 (m, 4H), 3.48-3.42 (m, 4H) 200 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(5-hydroxy- methyl-4-methyl- thiazol-2-yl)- methanol B C A MS: 467.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 7.70-7.63 (m, 2H), 7.55-7.50 (m, 2H), 7.44-7.39 (m, 1H), 7.22-7.19 (m, 1H), 6.81 (d, J = 4.5, 1H), 5.95 (d, J = 4.3, 1H), 5.35 (t, J = 5.6, 1H), 4.54 (d, J = 5.4, 2H), 3.80-3.75 (m, 4H), 3.47-3.42 (m, 4H), 2.22 (s, 3H) 201 1-(2-{[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}thiazol-4-yl)- ethanol B B B MS: 501.0/503.0 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11- (Cl isotopy, rel. peak 9.09 (m, 1H), 7.75-7.70 (m, 2H), 7.55-7.52 intensity ratio [%] 100:39) (m, 2H), 7.34-7.32 (m, 1H), 7.21-7.19 (m, 1H), 7.00-6.96 (m, 1H), 6.28-6.25 (m, 1H), 5.26-5.18 (m, 1H), 4.77-4.70 (m, 1H), 3.79- 3.75 (m, 4H), 3.47-3.43 (m, 4H), 1.36-1.30 (m, 3H) 202 [2-Chloro-4-fluoro- 5-(7-morpholin-4- ylquinazolin-4-yl)- phenyl]-(1-ethyl- 1H-pyrazol-4-yl)- methanol C B B MS: 468.0/470.0 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, (Cl isotopy, rel. peak 1H), 7.91-7.88 (m, 1H), 7.64 (d, J = 9.6, 1H), intensity ratio [%] 100:35) 7.59 (dd, J = 9.4, 3.2, 1H), 7.57-7.52 (m, 2H), 7.29 (s, 1H), 7.22-7.20 (m, 1H), 5.98 (d, J = 4.8, 1H), 5.93 (d, J = 4.8, 1H), 4.08-4.02 (m, 2H), 3.80-3.76 (m, 4H), 3.48-3.43 (m, 4H), 1.34-1.28 (m, 3H) 203 (4,5-Dimethyl- thiazol-2-yl)-[6- fluoro-5-(7- morpholin-4-yl- pyrido[4,3-d}- pyrimidin-4-yl)- pyridin-3-yl]- methanol (Ena 2) D D A MS: 453.2 (M + H.sup.+); R.sub.t see racemate 73.58 min, (HPLC, Chiralcel OD-H, hexane/2-propanol 90/10) 204 (R)-(4,5-Dimethyl- thiazol-2-yl)-[6- fluoro-5-(7- morpholin-4-yl- pyrido[4,3-d}- pyrimidin-4-yl)- pyridin-3-yl]- methanol (Ena 1) D D C MS: 453.2 (M + H.sup.+); R.sub.t see racemate 68.00 min, (HPLC, Chiralcel OD-H, hexane/2-propanol 90/10) 205 0 (4,5-Dimethyl- thiazol-2-yl)-[2- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- pyridin-3-yl]- methanol (Ena 1) C D C MS: 452.2 (M + H.sup.+); Rt see racemate 24.50 min, (HPLC, Chiralpak AD-H, ethanol) 206 (4,5-Dimethyl- thiazol-2-yl)-[2- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- pyridin-3-yl]- methanol (Ena 2) D B MS: 452.2 (M + H.sup.+); Rt see racemate 27.44 min, (HPLC, Chiralpak AD-H, ethanol)

Example 207

[4-Fluoro-2-methyl-5-(7-morpholinylquinazolin-4-yl)phenyl]thiazol-2-ylmethanol (EXAMPLE 207)

(145) ##STR00252##

(146) Methyl 4-fluoro-2-methyl-5-(7-morpholinylquinazolin-4-yl)benzoate was prepared analogously to the synthetic processes described under EXAMPLES 1 and 2 starting from 4-chloro-7-morpholin-4-ylquinazoline and methyl 4-fluoro-2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate.

(147) ##STR00253##

(148) [4-Fluoro-2-methyl-5-(7-morpholinylquinazolin-4-yl)phenyl]thiazol-2-ylmethanone was prepared analogously to the synthetic processes described under EXAMPLE 138 starting from thiazole and methyl 4-fluoro-2-methyl-5-(7-morpholinylquinazolin-4-yl)benzoate.

(149) ##STR00254##

(150) [4-Fluoro-2-methyl-5-(7-morpholinylquinazolin-4-yl)phenyl]thiazol-2-ylmethanol (EXAMPLE 207) was prepared analogously to the synthetic processes described under EXAMPLES 1 and 2 starting from [4-fluoro-2-methyl-5-(7-morpholinylquinazolin-4-yl)phenyl]thiazol-2-ylmethanone.

Example 208

[3-(2-Ethynyl-7-morpholinylquinazolin-4-yl)-4-fluorophenyl]thiazol-2-ylmethanol (EXAMPLE 208)

(151) ##STR00255##

(152) [3-(2-Chloro-7-morpholinylquinazolin-4-yl)-4-fluorophenyl]thiazol-2-ylmethanol was prepared analogously to the synthetic processes described under EXAMPLE 138 starting from (3-bromo-4-fluorophenyl)thiazol-2-ylmethanol and 4-(2,4-dichloroquinazolin-7-yl)morpholine.

(153) ##STR00256##

(154) [3-(2-Chloro-7-morpholinylquinazolin-4-yl)-4-fluorophenyl]thiazol-2-ylmethanol (102 mg, 0.225 mmol) was dissolved in oxygen-free N,N-dimethylformamide (4 ml) in an argon atmosphere. CuI (17 mg, 90 mol), (Ph.sub.3P).sub.2PdCl.sub.2 (63 mg, 90 mol), 2-diphenylphosphanylpyridine (95 mg, 0.359 mmol), DIPEA (765 l, 4.49 mmol) and triethylethynylsilane (275 l, 1.48 mmol) were subsequently added. The reaction mixture was then heated at a temperature of 140 C. for 1 h. For work-up, ethyl acetate (50 ml), water (10 ml) and saturated sodium chloride solution (15 ml) were added. The aqueous phase was separated off and extracted with ethyl acetate (20 ml). The combined organic phases were dried over sodium sulfate, filtered, and the filtrate was evaporated to dryness in vacuo. The residue was dissolved in dimethyl sulfoxide (2 ml) purified by means of RP chromatography (solvent: acetonitrile/water/0.1% by vol. of HCOOH, CombiFlash Rf 200). The suitable product fractions were combined, and the solvents were removed in a rotary evaporator, giving [4-fluoro-3-[7-morpholinyl-2-(2-triethylsilylethynyl)quinazolin-4-yl]phenyl]thiazol-2-ylmethanol (64 mg, 0.114 mmol, MS: 561.2 [M+H.sup.+], 50% yield) as wax-like solid.

(155) ##STR00257##

(156) [4-Fluoro-3-[7-morpholinyl-2-(2-triethylsilylethynyl)quinazolin-4-yl]phenyl]thiazol-2-ylmethanol (552 mg, 0.985 mmol) was dissolved in methanol (102 ml). Potassium hydroxide solution (1.0 M, 15 ml, 15 mmol) was subsequently added, and the mixture was stirred at room temperature for 90 min. When the reaction was complete, the mixture was carefully neutralised using hydrochloric acid (1.0 M, 15 ml, 15 mmol). Ethyl acetate (500 ml), water (100 ml) and saturated sodium chloride solution (150 ml) were subsequently added. The phases were separated, and the aqueous phase was extracted with ethyl acetate (100 ml). The combined organic phases were dried over sodium sulfate, filtered, and the filtrate was evaporated to dryness in vacuo. The residue, dissolved in dimethyl sulfoxide (8 ml), was purified by means of flash column chromatography (gradient: dichloromethane/0-5% by vol. of ethanol, CombiFlash Rf 200). The suitable product fractions were combined, and the solvents were removed in a rotary evaporator, giving [3-(2-ethynyl-7-morpholinylquinazolin-4-yl)-4-fluorophenyl]-thiazol-2-ylmethanol (EXAMPLE 208, 221 mg, 0.495 mmol, MS: 447.1 [M+H.sup.+], 50% yield) as solid.

(157) Compounds which were prepared analogously to EXAMPLES 207 and 208 can be found in Table 6 below.

(158) TABLE-US-00006 TABLE 6 Compounds of the formula (I) IC.sub.50 IC.sub.50 K.sub.i DNA- pDNA- [Kv1.11 No. Structural formula Name PK PK hERG] 207 [4-Fluoro-2- methyl-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thiazol-2- ylmethanol A B B MS: 437.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 7.71 (d, J = 3.2, 1H), 7.64 (d, J = 3.2, 1H), 7.62 (d, J = 7.5, 1H), 7.58-7.51 (m, 2H), 7.28 (d, J = 10.9, 1H), 7.19 (d, J = 2.1, 1H), 6.84 (s, 1H), 6.20 (s, 1H), 3.80-3.75 (m, 4H), 3.48- 3.43 (m, 4H), 2.49 (s, 3H) 208 [3-(2-Ethynyl-7- morpholin-4-yl- quinazolin-4-yl)- 4-fluoro-phenyl]- thiazol-2-yl- methanol B B D MS: 447.0 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 7.81- 7.47 (m, 6H), 7.46-7.36 (m, 1H), 7.18 (d, J = 2.4, 1H), 6.99 (d, J = 4.6, 1H), 6.08 (d, J = 4.3, 1H), 4.30 (s, 1H), 3.80-3.74 (m, 4H), 3.49- 3.41 (m, 4H) 209 0 [4-Fluoro-2- methyl-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thiazol-2- ylmethanol (Ena 1) D D A MS: 437.1 (M + H.sup.+); R.sub.t 1H NMR (400 MHz, DMSO-d6) ppm = 9.09 (s, 4.77 min (SFC, Chiracel OJ- 1H), 7.72 (d, J = 3.3, 1H), 7.68-7.59 (m, 2H), H, CO.sub.2/15% by vol. of 7.60-7.47 (m, 2H), 7.28 (d, J = 10.9, 1H), 7.19 methanol, 0.5% by vol. of (s, 1H), 6.99-6.71 (m, 1H) 6.20 (s, 1H), 3.82- diethylamine) 3.73 (m, 4H), 3.48-3.42 (m, 4H), 2.58-2.50 (m, 3H) 210 [4-Fluoro-2- methyl-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thiazol-2- ylmethanol (Ena 2) B B A MS: 437.1 (M + H.sup.+); R.sub.t 1H NMR (400 MHz, DMSO-d6) ppm = 9.09 (s, 6.01 min (SFC, Chiracel OJ- 1H), 7.72 (d, J = 3.3, 1H), 7.68-7.59 (m, 2H), H, CO.sub.2/15% by vol. of 7.60-7.47 (m, 2H), 7.28 (d, J = 10.9, 1H), 7.19 methanol, 0.5% by vol. of (s, 1H), 6.99-6.71 (m, 1H), 6.20 (s, 1H), 3.82- diethylamine) 3.73 (m, 4H), 3.48-3.42 (m, 4H), 2.58-2.50 (m, 3H) 211 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thiazol-2- ylmethanol B B A MS: 423.1 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 7.78-7.61 (m, 4H), 7.57-7.49 (m, 2H), 7.46-7.37 (m, 1H), 7.23-7.17 (m, 1H), 6.95 (s, 1H), 6.08 (s, 1H), 3.81-3.74 (m, 4H), 3.48- 3.41 (m, 4H) 212 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thiazol-2- ylmethanol (Ena 1) A D A MS: 423.1 (M + H.sup.+); R.sub.t 1H NMR (400 MHz, DMSO-d6) ppm = 9.10 (s, 15.65 min (SFC, Chiracel 1H), 7.73 (d, J = 3.2, 1H), 7.71-7.63 (m, 3H), OJ-H, CO.sub.2/10% by vol. of 7.55-7.49 (m, 2H), 7.44-7.38 (m, 1H), 7.22- methanol, 0.5% by vol. of 7.18 (m, 1H), 6.95 (d, J = 4.6, 1H), 6.08 (d, diethylamine) J = 4.5, 1H), 3.81-3.75 (m, 4H), 3.47-3.42 (m, 4H) 213 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thiazol-2- ylmethanol (Ena 2) A C A MS: 423.1 (M + H.sup.+); R.sub.t 1H NMR (400 MHz, DMSO-d6) ppm = 9.10 (s, 18.36 min (SFC, Chiracel 1H), 7.73 (d, J = 3.2, 1H), 7.72-7.65 (m, 2H), OJ-H, CO.sub.2/10% by vol. of 7.65-7.64 (m, 1H), 7.54-7.52 (m, 2H), 7.44- methanol, 0.5% by vol. of 7.39 (m, 1H), 7.21-7.19 (m, 1H), 6.96 (d, diethylamine) J = 4.6, 1H), 6.08 (d, J = 4.6, 1H), 3.80-3.75 (m, 4H), 3.46-3.42 (m, 4H) 214 [3-(2-Chloro-7- morpholin-4-yl- quinazolin-4-yl)- 4-fluoro-phenyl]- (2-methyl-2H- pyrazol-3-yl)- methanol B D B MS: 454.1/456.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 7.71- (Cl isotopy, rel. peak 7.59 (m, 3H), 7.58-7.51 (m, 2H), 7.50-7.41 intensity ratio [%] 100:35) (m, 1H), 7.31-7.26 (m, 1H), 7.18-7.12 (m, 1H), 5.99 (s, 1H), 5.95-5.90 (m, 1H), 3.78 (s, 3H), 3.78-3.73 (m, 4H), 3.52-3.45 (m, 4H) 215 [3-(2-Ethynyl-7- morpholin-4-yl- quinazolin-4-yl)- 4-fluorophenyl]- thiazol-2-yl- methanol (Ena 1) A C D MS: 447.1 (M + H.sup.+); R.sub.t 1H NMR (500 MHz, DMSO-d6) ppm = 7.73 (d, 10.67 min (HPLC, Chiralpak J = 3.2, 1H), 7.72-7.65 (m, 2H), 7.65 (d, J = 3.2, AD-H, n-heptane/40% by 1H), 7.53 (qd, J = 9.4, 2.7, 2H), 7.46-7.38 (m, vol. of 2-propanol 1H), 7.18 (d, J = 2.3, 1H), 6.97 (d, J = 4.6, 1H), 6.09 (d, J = 4.6, 1H), 4.30 (s, 1H), 3.80-3.74 (m, 4H), 3.49-3.43 (m, 4H) 216 [3-(2-Ethynyl-7- morpholin-4-yl- quinazolin-4-yl)- 4-fluorophenyl]- thiazol-2-yl- methanol (Ena 2) A D C MS: 447.1 (M + H.sup.+); R.sub.t 1H NMR (500 MHz, DMSO-d6) ppm = 7.73 (d, 13.14 min (HPLC, Chiralpak J = 3.2, 1H), 7.72-7.65 (m, 2H), 7.65 (d, J = 3.2, AD-H, n-heptane/40% by 1H), 7.53 (qd, J = 9.4, 2.7, 2H), 7.46-7.38 (m, vol. of 2-propanol 1H), 7.18 (d, J = 2.3, 1H), 6.97 (d, J = 4.6, 1H), 6.09 (d, J = 4.6, 1H), 4.30 (s, 1H), 3.80-3.74 (m, 4H), 3.49-3.43 (m, 4H)

Example 217

[2,4-Difluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]pyridin-3-ylmethanol (217)

(159) ##STR00268##

(160) 1,5-Dibromo-2,4-difluorobenzene (500 mg, 1.78 mmol) was dissolved in dry diethyl ether (10 ml) under argon. The reaction solution was cooled to ()65 C. by means of an acetone/dry-ice bath. n-Butyllithium (15% solution in n-hexane, 1.23 ml, 1.96 mmol) was added dropwise over the course of 15 min at a constant temperature of ()65 C., and the reaction solution was stirred at ()65 C. for a further 30 min. A pre-prepared solution of nicotinaldehyde (201 l, 2.14 mmol) in dry diethyl ether (5 ml) was subsequently added dropwise over a period of 15 min at ()65 C., and the reaction mixture was stirred for a further 10 min and then warmed slowly to 0 C. over a period of one hour. After termination of the reaction, saturated ammonium chloride solution (5 ml) and water (30 ml) were added to the reaction solution. The aqueous phase was extracted three times with t-butyl methyl ether. The combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated in a rotary evaporator. The crude product (oil) was purified by means of preparative RP column chromatography (solvent gradient water/acetonitrile/0.1% by vol. of trifluoroacetic acid [5.5 min], CombiFlash Rf 200). The suitable product fractions were combined and evaporated in vacuo. The aqueous residue was neutralised using saturated sodium hydrogencarbonate solution and extracted three times with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and evaporated to dryness in vacuo in a rotary evaporator, giving (5-bromo-2,4-difluorophenyl)-(3-pyridyl)methanol (215 mg, 0.717 mmol, MS: 300.0/302.0 [M+H+.sup.+], 40% yield) as colourless oil.

(161) ##STR00269##

(162) [2,4-Difluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]pyridin-3-ylmethanol (EXAMPLE 217) was obtained analogously to the synthetic processes for the preparation of 1-[5-(7-morpholin-4-ylquinazolin-4-yl)pyridin-3-yl]-1-thiazol-2-ylethanol (EXAMPLE 138) starting from (5-bromo-2,4-difluorophenyl)-(3-pyridyl)methanol.

(163) Compounds which were prepared analogously to EXAMPLE 217 can be found in Table 7 below.

(164) TABLE-US-00007 TABLE 7 Compounds of the formula (I) IC.sub.50 IC.sub.50 K.sub.i DNA- pDNA- [Kv1.11 No. Structural formula Name PK PK hERG] 217 0 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]pyridin-3-yl- methanol B A A MS: 435.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 8.62-8.59 (m, 1H), 8.47 (dd, J = 4.8, 1.6, 1H), 7.84 (t, J = 8.2, 1H), 7.77-7.72 (m, 1H), 7.55 (qd, J = 9.4, 2.8, 2H), 7.46 (t, J = 10.1, 1H), 7.39-7.34 (m, 1H), 7.21 (d, J = 2.4, 1H), 6.36 (d, J = 4.5, 1H), 6.06 (d, J = 4.5, 1H), 3.81-3.74 (m, 4H), 3.48-3.42 (m, 4H) 218 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]pyridin-2-yl- methanol B A B MS: 435.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.50-8.46 (m, 1H), 7.82 (td, J = 7.7, 1.8, 1H), 7.68 (t, J = 8.1, 1H), 7.64-7.59 (m, 1H), 7.57-7.50 (m, 2H), 7.43 (t, J = 10.1, 1H), 7.29- 7.24 (m, 1H), 7.21-7.17 (m, 1H), 6.34 (d, J = 5.0, 1H), 6.02 (d, J = 5.0, 1H), 3.82-3.72 (m, 4H), 3.48-3.41 (m, 4H). 219 6-{[2,4-Difluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-2-methyl- 2H-pyridazin-3-one B B B MS: 466.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 7.85 (t, J = 8.1, 1H), 7.61-7.51 (m, 3H), 7.47 (t, J = 10.1, 1H), 7.21 (d, J = 2.3, 1H), 6.94 (d, J = 9.6, 1H), 6.56 (d, J = 4.8, 1H), 5.85 (d, J = 4.8, 1H), 3.81-3.75 (m, 4H), 3.60 (s, 3H), 3.48-3.42 (m, 4H) 220 6-{[2,4-Difluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-2-methyl-2H- pyridazin-3-one D C A MS: 466.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 7.75 (d, J = 9.6, 1H), 7.67-7.61 (m, 1H), 7.51 (qd, J = 9.4, 2.6, 2H), 7.32 (t, J = 8.8, 1H), 7.20 (d, J = 2.3, 1H), 6.99 (d, J = 9.7, 1H), 6.64 (d, J = 5.1, 1H), 6.02 (d, J = 5.1, 1H), 3.78 (t, J = 4.9, 4H), 3.57 (s, 3H), 3.45 (t, J = 4.9, 4H) 221 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6-methoxy- pyridin-3-yl)methanol B B B MS: 465.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 8.17 (d, J = 2.4, 1H), 7.84 (t, J = 8.2, 1H), 7.63 (dd, J = 8.6, 2.5, 1H), 7.60-7.52 (m, 2H), 7.44 (t, J = 10.2, 1H), 7.21 (d, J = 2.3, 1H), 6.79 (d, J = 8.6, 1H), 6.22 (d, J = 4.0, 1H), 5.99 (d, J = 3.7, 1H), 3.83 (s, 3H), 3.80-3.76 (m, 4H), 3.47-3.43 (m, 4H) 222 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-[1,2,4]- triazolo[1,5-a]pyridin- 6-ylmethanol B B A MS: 475.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 8.98-8.95 (m, 1H), 8.49 (s, 1H), 7.88 (t, J = 8.1, 1H), 7.83-7.80 (m, 1H), 7.62-7.56 (m, 2H), 7.53 (dd, J = 9.5, 2.5, 1H), 7.48 (t, J = 10.1, 1H), 7.20 (d, J = 2.4, 1H), 6.52 (s, 1H), 6.17 (s, 1H), 3.82-3.74 (m, 4H), 3.49-3.41 (m, 4H) 223 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]imidazo- [1,2-a]pyrazin-6-yl- methanol C B A MS: 475.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.13 (s, 1H), 9.06-9.02 (m, 1H), 8.83 (t, J = 1.3, 1H), 8.25-8.22 (m, 1H), 7.86 (d, J = 1.0, 1H), 7.76 (t, J = 8.1, 1H), 7.63-7.56 (m, 2H), 7.52 (t, J = 10.1, 1H), 7.24 (d, J = 2.1, 1H), 6.53 (d, J = 4.7, 1H), 6.16 (d, J = 4.5, 1H), 3.87-3.80 (m, 4H), 3.54- 3.46 (m, 4H) 224 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(5-methoxy- pyridin-2-yl)methanol B B B MS: 465.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.20-8.17 (m, 1H), 7.68 (t, J = 8.1, 1H), 7.55-7.51 (m, 3H), 7.43-7.37 (m, 2H), 7.21- 7.18 (m, 1H), 6.23 (d, J = 4.9, 1H), 5.98 (d, J = 4.6, 1H), 3.80 (s, 3H), 3.80-3.74 (m, 4H), 3.48-3.41 (m, 4H)

Example 225

[2-Chloro-5-(5,6-dideuterio-7-morpholinylquinazolin-4-yl)-4-fluorophenyl]-(6-methoxypyridazin-3-yl)methanol (225)

(165) ##STR00278##

(166) Reaction of 5,6,8-trideuterio-7-morpholinyl-3H-quinazolin-4-one with phosphorus oxychloride gave 4-chloro-5,6-dideuterio-7-N-morpholinylquinazoline.

Example 237

[4-Fluoro-3-(7-morpholin-4-ylpyrido[3,2-d}pyrimidin-4-yl)phenyl]-(3-methylpyrazin-2-yl)methanol (237)

(167) ##STR00279##

Example 258

[2-Chloro-4-fluoro-5-[7-(2,2,3,3,5,5,6,6-octadeuteriomorpholin-4-yl)quinazolin-4-yl]phenyl]-(3-methoxypyrazin-2-yl)methanol (258)

(168) ##STR00280##

Examples 268 and 278

[4-Fluoro-3-(5-fluoro-7-morpholin-4-ylquinazolin-4-yl)phenyl]-(3-methylpyrazin-2-yl)methanol (268), [2-chloro-4-fluoro-5-(5-fluoro-7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol (278)

(169) ##STR00281##

Example 319

2-[2,4-Difluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-2-(3-methoxypyrazin-2-yl)acetamide (319)

(170) ##STR00282##

(171) [2,4-Difluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]acetonitrile (300 mg, 0.82 mmol) and 2-chloro-3-methoxypyrazine (297 mg, 1.97 mmol) were dissolved in tetrahydrofuran. Nitrogen was subsequently passed into the solution for a period of 10 min. Potassium tert-butoxide (193 mg, 1.72 mmol) was then added to the reaction solution, and the mixture was stirred at room temperature under an argon atmosphere for a period of 30 min. When the reaction was complete, the reaction mixture was neutralised using saturated NH.sub.4Cl solution, diluted with distilled water (30 ml) and extracted three times with dichloromethane (30 ml in each case). The organic phase was dried over NaSO.sub.4, filtered off with suction and evaporated to dryness in vacuo. The residue was purified by means of flash column chromatography (gradient: dichloromethane/0-5% by vol. of ethanol, CombiFlash Rf 200, 40 g silica column, =220 nm). The suitable product fractions were combined, and solvents were removed in a rotary evaporator, giving [2,4-difluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(3-methoxypyrazin-2-yl)acetonitrile (218 mg, 0.46 mmol; MS: 475.2 [M+H.sup.+], 56% yield) as solid.

(172) [2,4-Difluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(3-methoxypyrazin-2-yl)acetonitrile (218 mg, 0.46 mmol) was initially introduced in the reaction flask and subsequently dissolved with H.sub.2SO.sub.4 (95-98%, 3.53 ml, 64 mmol). The reaction solution was stirred at room temperature for 2.5 h. When the reaction was complete, ice (80 g) was added to the reaction solution. The mixture was subsequently carefully neutralised using NaOH solution (32%, 10.6 ml). The suspension obtained was diluted with distilled water (50 ml) and extracted three times with dichloromethane (100 ml in each case). The organic phase was dried over over a SO.sub.4, filtered off with suction and evaporated to dryness in vacuo. The residue was purified by means of flash column chromatography (gradient: dichloromethane/0-12% by vol. of ethanol, CombiFlash Rf 200, 40 g silica column, =220 nm). The suitable product fractions were combined, and solvents were removed in a rotary evaporator, giving 2-[2,4-difluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-2-(3-methoxypyrazin-2-yl)acetamide (182 mg, 0.37 mmol, MS: 493.4 [M+H.sup.+], 81% yield) as solid.

(173) Compounds which were prepared corresponding to EXAMPLES 225, 237, 258, 268, 278 and 319 and analogously to the synthesis sequences of EXAMPLES 1, 2, 37, 137, 121, 217 can be found in Table 8 below:

(174) TABLE-US-00008 IC.sub.50 IC.sub.50 K.sub.i DNA- pDNA- [Kv1.11 No. Structural formula Name PK PK hERG] 225 [2-Chloro-5-(5,6- dideuterio-7- morpholino- quinazolin-4-yl)-4- fluorophenyl]-(6- methoxypyridazin-3- yl)methanol B A A MS: 484.3/486.3 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, intensity ratio [%] 100:37) 1H), 7.91 (d, J = 7.8, 1H), 7.72-7.64 (m, 2H), 7.27- 7.17 (m, 2H), 6.61 (d, J = 5.0, 1H), 6.23 (d, J = 5.0, 1H), 4.00 (s, 3H), 3.81-3.72 (m, 4H), 3.49-3.36 (m, 4H). 226 [3-(5,6-Dideuterio-7- morpholino- quinazolin-4-yl)-4- fluorophenyl]-(3- methylpyrazin-2-yl)- methanol B A A MS: 434.4/436.4 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, intensity ratio [%] 100:40) 1H), 8.43 (s, 2H), 7.64-7.55 (m, 2H), 7.42-7.34 (m, 1H), 7.19 (s, 1H), 6.34-6.20 (m, 1H), 6.08 (s, 1H), 3.86-3.68 (m, 4H), 3.50-3.36 (m, 4H), 2.55 (s, 3H). 227 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- pyrido[3,2-d}- pyrimidin-4-yl)- phenyl]-(6-methoxy- pyridazin-3-yl)- methanol (Ena 1) B B A MS: 483.2/485.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:33); R.sub.t 8.37 min (HPLC, Chiralpak AD-H, n-heptane/90% by vol. of 2- propanol) 228 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- pyrido[3,2-d}- pyrimidin-4-yl)- phenyl]-(6-methoxy- pyridazin-3-yl)- methanol (Ena 2) D D A MS: 483.2/485.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:33); R.sub.t 12.45 min (HPLC, Chiralpak AD-H, n-heptane/90% by vol. of 2- propanol) 229 2-[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(3- methoxypyrazin-2- yl)-N-methyl- acetamide C B A MS: 523.3/525.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, intensity ratio [%] 100:40) 1H), 8.26 (q, J = 4.5, 1H), 8.13 (d, J = 2.8, 1H), 8.11 (d, J = 2.8, 1H), 7.73 (d, J = 9.6, 1H), 7.59 (dd, J = 9.4, 2.6, 1H), 7.56 (dd, J = 9.5, 2.3, 1H), 7.47 (d, J = 7.7, 1H), 7.20 (d, J = 2.2, 1H), 5.66 (s, 1H), 3.94 (s, 3H), 3.80-3.71 (m, 4H), 3.48-3.42 (m, 4H), 2.61 (d, J = 4.6, 3H). 230 2-(3-Chloro-pyridin- 2-yl)-2-[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-N-methyl- acetamide C C B* MS: 492.3/494.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, intensity ratio [%] 100:40) 1H), 8.51 (dd, J = 4.7, 1.4, 1H), 8.03 (q, J = 4.4, 1H), 7.92 (dd, J = 8.1, 1.5, 1H), 7.63 (dd, J = 9.4, 2.7, 1H), 7.58-7.54 (m, 3H), 7.41-7.33 (m, 2H), 7.20 (d, J = 2.4, 1H), 5.52 (s, 1H), 3.85-3.71 (m, 4H), 3.51- 3.40 (m, 4H), 2.60 (d, J = 4.6, 3H). 231 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- pyrido[3,2-d}- pyrimidin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol (Ena 2) C B A MS: 483.1/485.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:38); R.sub.t 8.72 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol) 232 0 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- pyrido[3,2-d}- pyrimidin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol (Ena 1) C D A MS: 483.1/485.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:38); R.sub.t 7.27 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol) 233 (S)-[4-Fluoro-3-(7- morpholin-4-yl- pyrido[3,2-d}- pyrimidin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)- methanol C D A MS: 433.1 (M + H.sup.+); R.sub.t 4.40 min (SFC, Chiralcel see racemate OD-H, CO.sub.2/40% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 234 (R)-[4-Fluoro-3-(7- morpholin-4-yl- pyrido[3,2-d}- pyrimidin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)- methanol A A A MS: 433.1 (M + H.sup.+); R.sub.t 3.01 min (SFC, Chiralcel see racemate OD-H, CO.sub.2/40% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 235 4-(4-Chloro-2-fluoro-5- imidazo[1,2-b]- pyridazin-6-ylmethyl- phenyl)-7-morpholin-4- ylquinazoline A A A* MS: 475.1/477.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, intensity ratio [%] 100:35) 1H), 8.22 (s, 1H), 8.07 (d, J = 9.4, 1H), 7.78-7.74 (m, 2H), 7.74-7.71 (m, 1H), 7.60 (dd, J = 9.4, 3.1, 1H), 7.54 (dd, J = 9.4, 2.5, 1H), 7.20 (d, J = 2.5, 1H), 7.16 (d, J = 9.4, 1H), 4.42 (s, 2H), 3.80-3.75 (m, 4H), 3.47-3.43 (m, 4H). 236 2-[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-imidazo- [1,2-b]pyridazin-6-yl- N-methylacetamide D C A* MS: 532.2/534.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, intensity ratio [%] 100:35) 1H), 8.56 (q, J = 4.5, 1H), 8.26 (s, 1H), 8.10 (d, J = 9.5, 1H), 7.81 (d, J = 9.5, 1H), 7.77 (d, J = 1.2, 1H), 7.74 (d, J = 7.6, 1H), 7.60 (dd, J = 9.4, 3.0, 1H), 7.55 (dd, J = 9.4, 2.5, 1H), 7.21 (d, J = 2.4, 1H), 7.12 (d, J = 9.5, 1H), 5.62 (s 1H), 3.81-3.75 (m, 4H), 3.48-3.40 (m, 4H), 2.65 (d, J = 4.6, 3H). 237 [4-Fluoro-3-(7- morpholin-4-yl- pyrido[3,2-d}- pyrimidin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)- methanol A A C MS: 433.3 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.18 (s, 1H), 9.02 (d, J = 2.9, 1H), 8.47-8.39 (m, 2H), 7.64 (dd, J = 6.7, 2.2, 1H), 7.59-7.50 (m, 1H), 7.45 (d, J = 2.9, 1H), 7.31 (dd, J = 9.7, 8.6, 1H), 6.28 (d, J = 5.4, 1H), 6.06 (d, J = 5.4, 1H), 3.81-3.76 (m, 4H), 3.56-3.50 (m, 4H), 2.55 (s, 3H). 238 [4-Fluoro-3-[7- (2,2,3,3,5,5,6,6- octadeuteriomorpholin- 4-yl)quinazolin-4- yl]phenyl]-(3-methyl- pyrazin-2-yl)- methanol (Ena 2) A A B MS: 440.4 (M + H.sup.+); R.sub.t 10.58 min (SFC, S. Racemat Chiralpak AD-H, CO.sub.2/30% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 239 [2-Chloro-4-fluoro-5- [7-(2,2,3,3,5,5,6,6- octadeuteriomorpholin- 4-yl)quinazolin-4- yl]phenyl]-(6- methoxypyridazin-3- yl)methanol (Ena 2) C D B MS: 490.3/492.2 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:38); R.sub.t 5.20 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 240 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- pyrido[3,2-d}- pyrimidin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)-methanol C B A MS: 467.3/469.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.23 (s, intensity ratio [%] 100:38) 1H), 9.06 (d, J = 2.9, 1H), 8.43 (d, J = 2.5, 1H), 8.33 (d, J = 2.5, 1H), 8.05 (d, J = 7.5, 1H), 7.54 (d, J = 9.2, 1H), 7.48 (d, J = 2.9, 1H), 6.65-6.27 (m, 1H), 6.25- 6.22 (m, 1H), 3.82-3.77 (m, 4H), 3.58-3.52 (m, 4H), 2.74 (s, 3H). 241 [2-Chloro-4-fluoro-5- [7-(2,2,3,3,5,5,6,6- octadeuteriomorpholin- 4-yl)quinazolin-4- yl]phenyl]-(3- methoxypyrazin-2- yl)methanol (Ena 2) A A C MS: 490.2/492.2 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:38); R.sub.t 6.47 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 242 00 [2-Chloro-4-fluoro-5- [7-(2,2,3,3,5,5,6,6- octadeuteriomorpholin- 4-yl)quinazolin-4- yl]phenyl]-(3- methoxypyrazin-2- yl)methanol (Ena 1) A A B MS: 490.2/492.2 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:35); R.sub.t 2.91 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 243 01 (S)-[4-Fluoro-3-[7- (2,2,3,3,5,5,6,6- octadeuteriomorpholin- 4-yl)quinazolin-4- yl]phenyl]-(3- methylpyrazin-2- yl)methanol (Ena 1) C B B MS: 440.4 (M + H.sup.+); R.sub.t 8.16 min (SFC, Chiralpak see racemate AD-H, CO.sub.2/30% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 244 02 [2-Chloro-4-fluoro-5- [7-(2,2,3,3,5,5,6,6- octadeuteriomorpholin- 4-yl)quinazolin-4- yl]phenyl]-(6- methoxypyridazin-3- yl)methanol (Ena 1) A A B MS: 490.1/492.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:33); R.sub.t 3.39 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 245 03 [4-Fluoro-3-(6- morpholin-4-yl- thieno[3,2-d}- pyrimidin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)- methanol (Ena 1) A A A* MS: 438.1 (M + H.sup.+); R.sub.t 4.70 min (SFC, Chiralcel see racemate OD-H, CO.sub.2/30% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 246 04 [4-Fluoro-3-(6- morpholin-4-yl- thieno[3,2-d}- pyrimidin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)- methanol (Ena 2) B B A* MS: 438.1 (M + H.sup.+); R.sub.t 7.04 min (SFC, Chiralcel see racemate OD-H, CO.sub.2/30% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 247 05 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- pyrido[3,2-d}- pyrimidin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol C C B MS: 483.1/485.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.22 (s, intensity ratio [%] 100:35) 1H), 9.04 (d, J = 2.9, 1H), 8.16 (d, J = 2.7, 1H), 8.08 (d, J = 2.7, 1H), 8.02 (d, J = 7.6, 1H), 7.51 (d, J = 9.3, 1H), 7.47 (d, J = 2.8, 1H), 6.32-6.28 (m, 2H), 4.00 (s, 3H), 3.82-3.77 (m, 4H), 3.57-3.52 (m, 4H). 248 06 (R)-[4-Fluoro-3-(5- fluoro-7-morpholin-4- ylquinazolin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)- methanol A A A MS: 450.1 (M + H.sup.+); R.sub.t 7.18 min (SFC, Chiralcel see racemate OD-H, CO.sub.2/25% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 249 07 [2-Chloro-4-fluoro-5- (5-fluoro-7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol (Ena 2) A A A* MS: 500.2/502.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:35); R.sub.t 7.94 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol) 250 08 [2-Chloro-4-fluoro-5- (5-fluoro-7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol (Ena 1) A A A* MS: 500.2/502.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:35); R.sub.t 3.46 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol) 251 09 (S)-[4-fluoro-3-(5- fluoro-7-morpholin-4- ylquinazolin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)- methanol B B A* MS: 450.1 (M + H.sup.+); R.sub.t 8.84 min (SFC, Chiralcel see racemate OD-H, CO.sub.2/25% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 252 0 [4-Fluoro-3-(5-fluoro- 7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol (Ena 2) A A A* MS: 466.2 (M + H.sup.+); R.sub.t 10.46 min (SFC, Chiralcel see racemate OD-H, CO.sub.2/25% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 253 [4-Fluoro-3-(5-fluoro- 7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol (Ena 1) C C A* MS: 466.2 (M + H.sup.+); R.sub.t 7.37 min (SFC, Chiralcel see racemate OD-H, CO.sub.2/25% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 254 2-[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-N-methyl-2- (3-methyl-pyrazin-2- yl)acetamide C D A* MS: 507.2/509.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, intensity ratio [%] 100:35) 1H), 8.41 (d, J = 2.6, 1H), 8.39 (d, J = 2.5, 1H), 8.30 (q, J = 4.5, 1H), 7.74 (d, J = 9.5, 1H), 7.59 (dd, J = 9.4, 2.6, 1H), 7.55 (dd, J = 9.5, 2.4, 1H), 7.47 (d, J = 7.7, 1H), 7.20 (d, J = 2.3, 1H), 5.66 (s, 1H), 3.78 (t, J = 5.8, 3.9, 4H), 3.46 (t, J = 4.9, 4H), 2.63 (d, J = 4.5, 3H), 2.52 (s, 3H). 255 [4-Fluoro-3-(5-fluoro- 7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6-methoxy- pyridazin-3-yl)- methanol (Ena 2) C A A* MS: 466.2 (M + H.sup.+); R.sub.t 10.43 min (SFC, see racemate Chiralpak AS-H, CO.sub.2/15% by vol. of methanol, 0.5% by vol. of diethylamine) 256 [4-Fluoro-3-(5-fluoro- 7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6-methoxy- pyridazin-3-yl)- methanol (Ena 1) A A A* MS: 466.2 (M + H.sup.+); R.sub.t 7.26 min (SFC, Chiralpak see racemate AS-H, CO.sub.2/15% by vol. of methanol, 0.5% by vol. of diethylamine) 257 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- pyrido[3,2-d}- pyrimidin-4-yl)- phenyl]-(6-methoxy- pyridazin-3-yl)- methanol B B A MS: 483.2/485.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.21 (s, intensity ratio [%] 100:33) 1H), 9.04 (d, J = 2.9, 1H), 7.96 (d, J = 7.5, 1H), 7.68 (d, J = 9.2, 1H), 7.58 (d, J = 9.3, 1H), 7.46 (d, J = 2.9, 1H), 7.22 (d, J = 9.1, 1H), 6.60 (d, J = 4.9, 1H), 6.23 (d, J = 4.9, 1H), 4.00 (s 3H), 3.84-3.76 (m, 4H), 3.57-3.51 (m, 4H). 258 [2-Chloro-4-fluoro-5- [7-(2,2,3,3,5,5,6,6- octadeuterio- morpholin-4-yl)- quinazolin-4-yl- ]phenyl]-(3-methoxy- pyrazin-2-yl)- methanol B A A* MS: 490.1/492.3 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.13 (s, intensity ratio [%] 100:36) 1H), 8.17 (d, J = 2.7, 1H), 8.11 (d, J = 2.7, 1H), 7.97 (d, J = 7.8, 1H), 7.67-7.58 (m, 2H), 7.56 (dd, J = 9.4, 2.6, 1H), 7.21 (d, J = 2.5, 1H), 6.34 (d, J = 5.9, 1H), 6.31 (d, J = 5.9, 1H), 4.00 (s, 3H). 259 [4-Fluoro-3-[7- (2,2,3,3,5,5,6,6- octadeuteriomorpholin- 4-yl)quinazolin-4- yl]phenyl]-(3-methyl- pyrazin-2-yl)- methanol A A A* MS: 440.4 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.44 (s, 2H), 7.63-7.55 (m, 2H), 7.53 (s, 2H), 7.42-7.34 (m, 1H), 7.19 (s, 1H), 6.30 (d, J = 5.3, 1H), 6.08 (d, J = 4.6, 1H), 2.55 (s, 3H). 260 [4-Fluoro-3-(5-fluoro- 7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6-methoxy- pyridazin-3-yl)- methanol A A A MS: 466.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (d, J = 6.1, 1H), 7.69 (d, J = 9.2, 1H), 7.66-7.48 (m, 2H), 7.37 (dt, J = 15.3, 2.7, 1H), 7.29 (ddd, J = 9.8, 8.5, 3.1, 1H), 7.21 (t, J = 9.2, 1H), 7.08 (d, J = 2.4, 1H), 6.57-6.43 (m, 1H), 6.00 (d, J = 4.4, 1H), 4.00 (d, J = 2.9, 3H), 3.81-3.69 (m, 4H), 3.53-3.40 (m, 4H). 261 2-[2-Chloro-4-fluoro- 5-(5-fluoro-7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(3- methoxy-pyrazin-2- yl)acetamide C B B MS: 527.2/529.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (400 MHz, DMSO-d6) ppm = 9.07 (s, intensity ratio [%] 100:35) 1H), 8.10 (d, J = 2.8, 1H), 8.07 (d, J = 2.8, 1H), 7.56 (d, J = 7.7, 1H), 7.51 (d, J = 9.7, 1H), 7.41-6.85 (m, 5H), 3.96 (s, 3H), 3.82-3.74 (m, 4H), 3.52-3.45 (m, 4H). 262 0 [2-Chloro-4-fluoro-5- [7-(2,2,3,3,5,5,6,6- octadeuteriomorpholin- 4-yl)quinazolin-4- yl]phenyl]-(6- methoxypyridazin-3- yl)methanol A A A* MS: 490.2/492.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, intensity ratio [%] 100:36) 1H), 7.91 (d, J = 7.8, 1H), 7.71-7.64 (m, 2H), 7.59 (dd, J = 9.4, 3.4, 1H), 7.54 (dd, J = 9.4, 2.6, 1H), 7.23-7.19 (m, 2H), 6.63 (d, J = 5.0, 1H), 6.23 (d, J = 5.0, 1H), 4.00 (s, 3H). 263 [2-Chloro-4-fluoro-5- (5-fluoro-7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6-methoxy- pyridazin-3-yl)- methanol (Ena 2) C D A* MS: 500.1/502.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:30); R.sub.t 6.17 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 264 [2-Chloro-4-fluoro-5- (6-morpholin-4-yl- thieno[3,2-d}- pyrimidin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)- methanol A A A* MS: 472.1/474.0 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 8.93 (s, intensity ratio [%] 100:40) 1H), 8.43 (d, J = 2.5, 1H), 8.33 (d, J = 2.4, 1H), 8.11 (d, J = 7.9, 1H), 7.63 (d, J = 9.9, 1H), 6.56 (s, 1H), 6.47 (d, J = 6.0, 1H), 6.23 (d, J = 4.6, 1H), 3.79- 3.71 (m, 4H), 3.48-3.39 (m, 4H), 2.73 (s, 3H). 265 [4-Fluoro-3-(6- morpholin-4-yl- thieno[3,2-d}- pyrimidin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)- methanol A A A* MS: 438.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 8.88 (s, 1H), 8.46-8.42 (m, 2H), 7.67 (dd, J = 7.0, 2.3, 1H), 7.60-7.55 (m, 1H), 7.38 (dd, J = 10.3, 8.6, 1H), 6.52 (s, 1H), 6.32 (d, J = 5.4, 1H), 6.08-6.05 (m, 1H), 3.79-3.70 (m, 4H), 3.44-3.37 (m, 4H), 2.54 (s, 3H). 266 [2-Chloro-4-fluoro-5- (5-fluoro-7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol A A A* MS: 500.2/502.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (400 MHz, 90 C., DMSO-d6) ppm = 9.08 intensity ratio [%] 100:35) (s, 1H), 8.11 (d, J = 2.7, 1H), 8.07 (d, J = 2.7, 1H), 7.90 (d, J = 8.0, 1H), 7.39 (d, J = 9.7, 1H), 7.29 (dd, J = 15.2, 2.3, 1H), 7.07 (d, J = 2.3, 1H), 6.30 (s, 1H), 3.96 (s, 3H), 3.80-3.72 (m, 4H), 3.51-3.44 (m, 4H). 267 [4-Fluoro-3-(5-fluoro- 7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol A A A* MS: 466.2 (M + H.sup.+) 1H NMR (400 MHz, 90 C., DMSO-d6) ppm = 9.05 (s, 1H), 8.15 (d, J = 2.5, 1H), 8.11 (d, J = 2.5, 1H), 7.62-7.44 (m, 2H), 7.30-7.12 (m, 2H), 7.05 (d, J = 2.2, 1H), 6.09-5.95 (m, 2H), 3.91 (s, 3H), 3.81- 3.70 (m, 4H), 3.52-3.41 (m, 4H). 268 [4-Fluoro-3-(5-fluoro- 7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)- methanol A A A* MS: 450.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, 1H), 8.45 (s, 2H), 7.63-7.56 (m, 1H), 7.56-7.46 (m, 1H), 7.46-7.34 (m, 1H), 7.34-7.22 (m, 1H), 7.08 (s, 1H), 6.36-6.27 (m, 1H), 6.06 (d, J = 5.4, 1H), 3.81-3.73 (m, 4H), 3.53-3.43 (m, 4H), 2.53 (s, 3H). 269 2-[2-Chloro-4-fluoro- 5-(6-morpholin-4-yl- thieno[3,2-d}- pyrimidin-4-yl)- phenyl]-2-(3-methyl- pyrazin-2-yl)- acetamide B B A* MS: 499.1/501.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 8.87 (s, intensity ratio [%] 100:39) 1H), 8.43 (d, J = 2.6, 1H), 8.40 (d, J = 2.7, 1H), 7.82- 7.78 (m, 1H), 7.74 (d, J = 10.0, 1H), 7.55 (d, J = 7.8, 1H), 7.41-7.36 (m, 1H), 6.53 (s, 1H), 5.63 (s, 1H), 3.79-3.73 (m, 4H), 3.43-3.38 (m, 4H), 2.51 (s, 3H). 270 2-[4-Fluoro-3-(6- morpholin-4-yl- thieno[3,2-d}- pyrimidin-4-yl)- phenyl]-2-(3-methyl- pyrazin-2-yl)- acetamide B C A* MS: 465.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 8.88 (s, 1H), 8.42-8.37 (m, 2H), 7.67 (dd, J = 7.1, 2.3, 1H), 7.61-7.55 (m, 2H), 7.41-7.34 (m, 1H), 7.25- 7.19 (m, 1H), 6.53 (s, 1H), 5.40 (s, 1H), 3.79- 3.71 (m, 4H), 3.44-3.39 (m, 4H), 2.53 (s, 3H). 271 [2-Chloro-4-fluoro-5- (5-fluoro-7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6-methoxy- pyridazin-3-yl)- methanol (Ena 1) A A A MS: 500.1/502.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (400 MHz, DMSO-d6/DMSO, 120 C.) ppm = intensity ratio [%] 100:32); R.sub.t 4.25 min (SFC, 9.05 (s, 1H), 7.84 (d, J = 7.7 Hz, 1H), 7.60 (d, J = Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 9.0 Hz, 1H), 7.40 (d, J = 9.5 Hz, 1H), 7.23 (d, J = 0.5% by vol. of diethylamine) 14.5 Hz, 1H), 7.11 (d, J = 9.1 Hz, 1H), 7.06 (s, 1H), 6.24 (d, J = 4.7 Hz, 1H), 6.16 (d, J = 4.7 Hz, 1H), 4.02 (s, 3H), 3.80-3.72 (m, 4H), 3.51-3.43 (m, 4H). 272 0 2-[2-Chloro-4-fluoro- 5-(6-morpholin-4-yl- thieno[3,2-d}- pyrimidin-4-yl)- phenyl]-2-(6- methoxy-pyridazin-3- yl)acetamide B B A* MS: 515.2/517.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (400 MHz, DMSO-d6) ppm = 8.89 (s, intensity ratio [%] 100:41) 1H), 7.94 (s, 1H), 7.81 (d, J = 7.7, 1H), 7.74 (d, J = 10.0, 1H), 7.47 (d, J = 9.2, 1H), 7.40 (s, 1H), 7.19 (d, J = 9.2, 1H), 6.53 (s, 1H), 5.65 (s, 1H), 4.00 (s, 3H), 3.79-3.71 (m, 4H), 3.45-3.39 (m, 4H). 278 [2-Chloro-4-fluoro-5- (5-fluoro-7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6-methoxy- pyridazin-3-yl)- methanol A A A* MS: 500.2/502.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (400 MHz, 120 C., DMSO-d6) ppm = 9.05 intensity ratio [%] 100:35) (s, 1H), 7.84 (d, J = 7.8, 1H), 7.60 (d, J = 9.1, 1H), 7.40 (d, J = 9.6, 1H), 7.23 (dd, J = 15.2, 2.5, 1H), 7.11 (d, J = 9.1, 1H), 7.06 (d, J = 2.5, 1H), 6.25 (d, J = 5.1, 1H), 6.16 (d, J = 5.1, 1H), 4.03 (s, 3H), 3.80- 3.73 (m, 4H), 3.49-3.43 (m, 4H). 279 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-[1,2,4]- triazolo[1,5-a]- pyrazin-8-ylmethanol B C A* MS: 458.2 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 9.03 (d, J = 4.5, 1H), 8.76 (s, 1H), 8.25 (d, J = 4.5, 1H), 7.84-7.76 (m, 2H), 7.59-7.51 (m, 2H), 7.39 (dd, J = 9.9, 8.5, 1H), 7.20 (d, J = 2.1, 1H), 6.48 (s, 1H), 3.82-3.75 (m, 4H), 3.51-3.43 (m, 4H). 280 2-[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-[1,2,4]- triazolo[1,5-a]- pyrazin-8-yl- acetamide C D A* MS: 485.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 9.02 (d, J = 4.5, 1H), 8.74 (s, 1H), 8.21 (d, J = 4.5, 1H), 7.79-7.75 (m, 1H), 7.74-7.69 (m, 2H), 7.64 (dd, J = 9.4, 2.9, 1H), 7.56 (dd, J = 9.5, 2.5, 1H), 7.45-7.40 (m, 1H), 7.31-7.27 (m, 1H), 7.20 (d, J = 2.4, 1H), 5.89 (s, 1H), 3.81-3.74 (m, 4H), 3.49-3.41 (m, 4H). 282 [4-Fluoro-3-(6-fluoro- 7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6-methoxy- pyridazin-3-yl)- methanol D D A* MS: 466.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.24 (s, DELETE 1H), 7.74-7.63 (m, 3H), 7.48-7.39 (m, 2H), 7.34 (dd, J = 13.6, 3.1, 1H), 7.21 (d, J = 9.2, 1H), 6.53 (d, J = 4.3, 1H), 6.03 (d, J = 4.4, 1H), 4.00 (s, 3H), 3.83-3.77 (m, 4H), 3.36-3.27 (m, 4H). 283 [4-Fluoro-3-(6-fluoro- 7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)- methanol C D A MS: 450.2 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.23 (s, DELETE 1H), 8.46-8.41 (m, 2H), 7.66-7.58 (m, 2H), 7.49-7.31 (m, 3H), 6.32 (d, J = 5.5, 1H), 6.10 (d, J = 5.5, 1H), 3.84-3.78 (m, 4H), 3.36-3.27 (m, 4H), 2.57 (s, 3H). 284 2-[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-thieno- [2,3-d}pyridazin-7-yl- acetamide B D A* MS: 501.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.59 (s, 1H), 9.09 (s, 1H), 8.24 (d, J = 5.3, 1H), 7.92 (s, 1H), 7.73-7.65 (m, 3H), 7.57 (dd, J = 9.4, 3.1, 1H), 7.50 (dd, J = 9.5, 2.5, 1H), 7.47-7.36 (m, 2H), 7.19 (d, J = 2.5, 1H), 5.72 (s, 1H), 3.84-3.73 (m, 4H), 3.46-3.41 (m, 4H), 9.09-9.09 (m, 0H). 285 2-[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-thieno- [2,3-d}pyridazin-4-yl- acetamide B D B MS: 501.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.83-9.79 (m, 1H), 9.08 (s, 1H), 8.30 (d, J = 5.4, 1H), 7.81- 7.75 (m, 2H), 7.75-7.68 (m, 2H), 7.56 (dd, J = 9.4, 3.1, 1H), 7.49 (dd, J = 9.4, 2.6, 1H), 7.40 (dd, J = 9.8, 8.4, 1H), 7.32 (s, 1H), 7.19 (d, J = 2.5, 1H), 5.90 (s, 1H), 3.81-3.74 (m, 4H), 3.47-3.40 (m, 4H). 286 (6-Chloro-3-methoxy- pyridazin-4-yl)-[4- fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol (Ena 1) C C A* MS: 482.1/484.2 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:36); R.sub.t 5.83 min (SFC, Chiralpak AS-H, CO.sub.2/20% by vol. of methanol, 0.5% by vol. of diethylamine) 288 6-{[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-2-methyl-4,5- dihydro-2H-pyridazin- 3-one C C A* MS: 484.2/486.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, intensity ratio [%] 100:35) 1H), 7.84 (d, J = 7.8, 1H), 7.68 (d, J = 9.5, 1H), 7.57 (dd, J = 9.4, 2.8, 1H), 7.54 (dd, J = 9.5, 2.4, 1H), 7.21 (d, J = 2.3, 1H), 6.42 (s, 1H), 5.57 (s, 1H), 3.81-3.75 (m, 4H), 3.47-3.43 (m, 4H), 3.16 (s, 3H), 2.61-2.51 (m, 1H), 2.43-2.28 (m, 3H). 289 0 2-[2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(3-chloro- pyridin-2-yl)-acetamide A B B MS: 512.2/514.2/516.2 (M + H.sup.+) (Cl.sub.2 isotopy, rel. 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, peak intensity ratio [%] 100:71:21) 1H), 8.44 (dd, J = 4.7, 1.5, 1H), 7.95 (dd, J = 8.1, 1.5, 1H), 7.76 (s, 1H), 7.72 (d, J = 9.6, 1H), 7.58 (dd, J = 9.4, 2.9, 1H), 7.54 (dd, J = 9.5, 2.5, 1H), 7.41 (d, J = 7.6, 1H), 7.35 (dd, J = 8.1, 4.7, 1H), 7.28 (s, 1H), 7.19 (d, J = 2.4, 1H), 5.81 (s, 1H), 3.80- 3.75 (m, 4H), 3.48-3.42 (m, 4H). 290 2-(4-Chlorothieno- [2,3-d}pyridazin-7-yl)- 2-[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]acetamide B C D MS: 535.3/537.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, intensity ratio [%] 100:41) 1H), 8.41 (d, J = 5.4, 1H), 7.94 (s, 1H), 7.71-7.65 (m, 3H), 7.56 (dd, J = 9.4, 3.1, 1H), 7.51 (dd, J = 9.4, 2.5, 1H), 7.48-7.40 (m, 2H), 7.20 (d, J = 2.4, 1H), 5.75 (s, 1H), 3.82-3.73 (m, 4H), 3.48- 3.40 (m, 4H). 291 2-(7-Chlorothieno- [2,3-d}pyridazin-4-yl)- 2-[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]acetamide B C D MS: 535.2/537.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, intensity ratio [%] 100:41) 1H), 8.43 (d, J = 5.4, 1H), 7.86 (d, J = 5.4, 1H), 7.77 (s, 1H), 7.74-7.67 (m, 2H), 7.56 (dd, J = 9.4, 3.1, 1H), 7.50 (dd, J = 9.5, 2.5, 1H), 7.44-7.35 (m, 2H), 7.19 (d, J = 2.4, 1H), 5.92 (s, 1H), 3.81-3.74 (m, 4H), 3.47-3.40 (m, 4H). 292 6-{Carbamoyl-[4- fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]methyl}- pyrazine-2-carboxylic acid amide C D A MS: 488.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, 1H), 9.06 (s, 1H), 8.90 (s, 1H), 8.08-8.01 (m, 1H), 7.99-7.93 (m, 1H), 7.85-7.77 (m, 2H), 7.77-7.71 (m, 1H), 7.59 (dd, J = 9.4, 3.6, 1H), 7.52 (dd, J = 9.5, 2.5, 1H), 7.46-7.39 (m, 1H), 7.38-7.32 (m, 1H), 7.20 (d, J = 2.5, 1H), 5.39 (s, 1H), 3.80-3.75 (m, 4H), 3.47-3.42 (m, 4H). 293 2-[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-pyridin-3- ylacetamide B C A MS: 478.2/480.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, intensity ratio [%] 100:30) 1H), 8.49 (s, 1H), 8.46 (d, J = 3.9, 1H), 7.94 (s, 1H), 7.74 (d, J = 9.5, 1H), 7.67 (d, J = 7.7, 1H), 7.66- 7.63 (m, 1H), 7.56 (dd, J = 9.4, 3.2, 1H), 7.53 (dd, J = 9.5, 2.4, 1H), 7.37 (dd, J = 7.9, 4.8, 1H), 7.33 (s, 1H), 7.20 (d, J = 2.3, 1H), 5.41 (s, 1H), 3.81-3.74 (m, 4H), 3.49-3.42 (m, 4H). 294 2-[2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-pyridin-3- ylacetamide B D A MS: 462.3 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, 1H), 8.53 (d, J = 2.3, 1H), 8.48 (dd, J = 4.8, 1.6, 1H), 7.89 (s, 1H), 7.72 (dt, J = 8.0, 2.0, 1H), 7.61 (t, J = 8.2, 1H), 7.59-7.48 (m, 3H), 7.38 (dd, J = 7.9, 4.7, 1H), 7.32 (s, 1H), 7.19 (d, J = 2.3, 1H), 5.31 (s, 1H), 3.82-3.73 (m, 4H), 3.47-3.42 (m, 4H). 295 2-[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-pyridin-3- ylacetamide C D A MS: 444.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.55 (s, 1H), 8.47 (s, 1H), 7.82 (s, 1H), 7.79 (d, J = 8.0, 1H), 7.62-7.56 (m, 2H), 7.56-7.49 (m, 2H), 7.45-7.35 (m, 2H), 7.25 (s, 1H), 7.20 (d, J = 2.0, 1H), 5.12 (s, 1H), 3.80-3.74 (m, 4H), 3.47- 3.41 (m, 4H). 296 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6-methyl- pyrazin-2-yl)- methanol C C A MS: 432.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 8.66 (s, 1H), 8.43 (s, 1H), 7.68-7.63 (m, 2H), 7.54-7.49 (m, 2H), 7.42-7.35 (m, 1H), 7.21-7.18 (m, 1H), 6.40 (d, J = 4.3, 1H), 5.87 (d, J = 4.3, 1H), 3.81-3.74 (m, 4H), 3.47-3.41 (m, 4H), 2.46 (s, 3H). 297 2-(5-Chloro-pyridin- 3-yl)-2-[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]acetamide C D C MS: 478.3/480.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, intensity ratio [%] 100:38) 1H), 8.54 (d, J = 2.4, 1H), 8.52 (d, J = 1.9, 1H), 7.90- 7.87 (m, 1H), 7.85 (s, 1H), 7.61 (tt, J = 6.9, 2.3, 2H), 7.53 (qd, J = 9.4, 2.8, 2H), 7.47-7.39 (m, 1H), 7.33 (s, 1H), 7.20 (d, J = 2.3, 1H), 5.16 (s, 1H), 3.82-3.73 (m, 4H), 3.48-3.40 (m, 4H). 298 2-[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-[1,2,4]- triazolo[4,3-a]pyridin- 5-ylacetamide C D A MS: 518.2/520.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.21 (d, intensity ratio [%] 100:35) J = 0.8, 1H), 9.08 (s, 1H), 8.13 (s, 1H), 7.88 (d, J = 9.5, 1H), 7.79 (d, J = 9.2, 1H), 7.73 (s, 1H), 7.57- 7.48 (m, 3H), 7.38 (dd, J = 9.2, 6.9, 1H), 7.19 (d, J = 2.3, 1H), 6.57 (d, J = 6.9, 1H), 5.84 (s, 1H), 3.80- 3.75 (m, 4H), 3.48-3.42 (m, 4H). 299 0 2-[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-pyrrolo- [2,1-f][1,2,4]triazin-4- ylacetamide C D D MS: 484.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 13.68 (d, J = 4.0, 1H), 9.09 (s, 1H), 7.84-7.74 (m, 2H), 7.57- 7.46 (m, 3H), 7.46-7.39 (m, 1H), 7.31-7.25 (m, 1H), 7.24-7.16 (m, 1H), 7.02 (s, 1H), 6.21 (dd, J = 4.4, 2.7, 1H), 6.08 (s, 1H), 4.81 (dd, J = 4.3, 1.7, 1H), 3.90-3.70 (m, 4H), 3.53-3.38 (m, 4H). 300 2-[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-pyridazin-3- ylacetamide C D A MS: 479.2/481.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.14 (dd, intensity ratio [%] 100:33) J = 4.9, 1.6, 1H), 9.10 (s, 1H), 8.03 (s, 1H), 7.76 (d, J = 9.6, 1H), 7.71 (d, J = 7.6, 1H), 7.65 (dd, J = 8.5, 4.9, 1H), 7.60 (dd, J = 9.4, 3.4, 1H), 7.53 (dd, J = 5.6, 2.1, 1H), 7.52 (dd, J = 4.7, 2.0, 1H), 7.43 (s, 1H), 7.20 (d, J = 2.5, 1H), 5.78 (s, 1H), 3.78 (dd, J = 5.8, 4.0, 4H), 3.46 (dd, J = 6.0, 3.9, 4H). 301 2-[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(3,5- dimethyl-pyrazin-2- yl)acetamide C B A MS: 507.2/509.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, intensity ratio [%] 100:35) 1H), 8.25 (s, 1H), 7.75-7.69 (m, 2H), 7.58 (dd, J = 9.4, 3.0, 1H), 7.54 (dd, J = 9.5, 2.5, 1H), 7.47 (d, J = 7.7, 1H), 7.28 (s, 1H), 7.19 (d, J = 2.4, 1H), 5.60 (s, 1H), 3.81-3.74 (m, 4H), 3.49-3.42 (m, 4H), 2.49 (s, 3H), 2.41 (s, 3H). 302 (6-Amino-pyrazin-2- yl)-[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol B C A MS: 433.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 7.91 (s, 1H), 7.74 (s, 1H), 7.63-7.56 (m, 2H), 7.54-7.51 (m, 2H), 7.39-7.34 (m, 1H), 7.21-7.19 (m, 1H), 6.36 (s, 2H), 6.10 (d, J = 4.3, 1H), 5.60 (d, J = 4.3, 1H), 3.81-3.74 (m, 4H), 3.47- 3.41 (m, 4H). 303 2-[2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(3-methyl- pyrazin-2-yl)- acetamide C C B MS: 475.2/477.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.05 (s, intensity ratio [%] 100:38) 1H), 8.43-8.37 (m, 2H), 7.87 (d, J = 9.4, 1H), 7.80 (s, 1H), 7.75-7.65 (m, 3H), 7.51 (dd, J = 9.5, 2.6, 1H), 7.33 (s, 1H), 7.19 (d, J = 2.5, 1H), 5.71 (s, 1H), 3.85-3.74 (m, 4H), 3.52-3.39 (m, 4H), 2.55 (s, 3H). 304 2-[2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(3- methoxy-pyrazin-2- yl)acetamide C C A MS: 491.3/493.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.06 (s, intensity ratio [%] 100:38) 1H), 8.12 (d, J = 2.8, 1H), 8.10 (d, J = 2.8, 1H), 7.89 (d, J = 9.4, 1H), 7.79-7.75 (m, 1H), 7.73-7.69 (m, 2H), 7.67 (d, J = 8.1, 1H), 7.52 (dd, J = 9.5, 2.6, 1H), 7.27-7.23 (m, 1H), 7.20 (d, J = 2.6, 1H), 5.71 (s, 1H), 3.95 (s, 3H), 3.81-3.75 (m, 4H), 3.49-3.41 (m, 4H). 305 2-[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(3- methoxy-pyrazin-2- yl)acetamide C C A MS: 475.3 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.13 (d, J = 2.8, 1H), 8.10 (d, J = 2.8, 1H), 7.63 (dd, J = 9.4, 2.8, 1H), 7.61-7.52 (m, 4H), 7.41- 7.35 (m, 1H), 7.20 (d, J = 2.4, 1H), 7.11 (s, 1H), 5.34 (s, 1H), 3.93 (s, 3H), 3.82-3.74 (m, 4H), 3.48-3.41 (m, 4H). 306 2-[2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(6- methoxy-pyridazin-3- yl)acetamide C D A MS: 493.3 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 7.90 (s, 1H), 7.71 (t, J = 8.2, 1H), 7.61-7.49 (m, 4H), 7.37 (s, 1H), 7.20 (d, J = 2.4, 1H), 7.18 (d, J = 9.2, 1H), 5.57 (s, 1H), 4.00 (s, 3H), 3.81-3.74 (m, 4H), 3.49-3.41 (m, 4H). 307 2-[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(3- methoxypyridazin-4- yl)acetamide B C A MS: 509.2/511.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, intensity ratio [%] 100:39) 1H), 8.80 (d, J = 4.7, 1H), 8.02 (s, 1H), 7.80 (d, J = 9.5, 1H), 7.59 (dd, J = 9.4, 3.3, 1H), 7.53 (dd, J = 9.5, 2.5, 1H), 7.46 (d, J = 7.5, 1H), 7.42 (s, 1H), 7.20 (d, J = 2.4, 1H), 7.08 (dd, J = 4.7, 0.5, 1H), 5.46 (s, 1H), 4.07 (s, 3H), 3.80-3.76 (m, 4H), 3.49- 3.43 (m, 4H). 308 2-[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(6- methoxypyridazin-3- yl)acetamide C D A MS: 475.3 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 7.87 (s, 1H), 7.67 (d, J = 9.2, 1H), 7.64-7.57 (m, 2H), 7.57-7.49 (m, 2H), 7.46-7.38 (m, 1H), 7.31 (s, 1H), 7.20 (d, J = 2.2, 1H), 7.18 (d, J = 9.2, 1H), 5.40 (s, 1H), 4.00 (s, 3H), 3.78 (dd, J = 5.8, 3.9, 4H), 3.44 (dd, J = 5.8, 4.1, 4H). 309 0 2-[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-[3H- pyrrolo[2,1-f][1,2,4]- triazin-(4E)-ylidene]- acetamide D D D MS: 518.2/520.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 13.76 (d, intensity ratio [%] 100:37) J = 3.9, 1H), 9.07 (s, 1H), 7.86 (d, J = 9.7, 1H), 7.84- 7.76 (m, 2H), 7.56 (d, J = 7.8, 1H), 7.51 (dd, J = 9.5, 2.5, 1H), 7.32 (dd, J = 2.7, 1.7, 1H), 7.18 (d, J = 2.4, 1H), 6.99 (s, 1H), 6.37 (s, 1H), 6.26 (dd, J = 4.4, 2.7, 1H), 4.87 (dd, J = 4.4, 1.7, 1H), 3.81- 3.74 (m, 4H), 3.49-3.42 (m, 4H). 310 2-[2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(6- methoxy-pyridazin-3- yl)acetamide D D B MS: 491.2/493.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.07 (s, intensity ratio [%] 100:35) 1H), 7.97 (s, 1H), 7.89-7.85 (m, 2H), 7.73 (dd, J = 8.2, 2.1, 1H), 7.70 (d, J = 8.2, 1H), 7.52 (dd, J = 9.5, 2.6, 1H), 7.46 (d, J = 9.2, 1H), 7.39 (s, 1H), 7.21 (d, J = 2.5, 1H), 7.18 (d, J = 9.2, 1H), 5.72 (s, 1H), 4.01 (s, 3H),3.82-3.75 (m, 4H), 3.48-3.42 (m, 4H). 311 2-[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(1-methyl- 6-oxo-1,6-dihydro- pyridazin-3-yl)- acetamide D D A MS: 509.3/511.3 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, intensity ratio [%] 100:38) 1H), 7.92 (s, 1H), 7.76 (d, J = 9.5, 1H), 7.68 (d, J = 7.5, 1H), 7.58 (dd, J = 9.4, 3.1, 1H), 7.54 (dd, J = 9.5, 2.5, 1H), 7.41 (s, 1H), 7.33 (d, J = 9.6, 1H), 7.21 (d, J = 2.4, 1H), 6.90 (d, J = 9.6, 1H), 5.33 (s, 1H), 3.81-3.75 (m, 4H), 3.59 (s, 3H), 3.49-3.42 (m, 4H). 312 2-[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(1-methyl- 6-oxo-1,6-dihydro- pyridin-2-yl)- acetamide D D A MS: 508.3/510.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, intensity ratio [%] 100:38) 1H), 8.04 (s, 1H), 7.83 (d, J = 9.4, 1H), 7.62-7.44 (m, 3H), 7.42-7.27 (m, 2H), 7.19 (d, J = 2.4, 1H), 6.36 (dd, J = 9.1, 1.3, 1H), 5.90 (dd, J = 7.1, 1.3, 1H), 5.48 (s, 1H), 3.77 (dd, J = 5.8, 4.0, 4H), 3.52-3.42 (m, 4H), 3.40 (s, 3H). 313 2-(3-Chloro-pyridin- 2-yl)-2-[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]acetamide C C B MS: 478.2/480.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, intensity ratio [%] 100:36) 1H), 8.51 (dd, J = 4.7, 1.5, 1H), 7.93 (dd, J = 8.1, 1.5, 1H), 7.64 (dd, J = 9.4, 2.9, 1H), 7.61-7.53 (m, 4H), 7.39 (dd, J = 9.9, 8.7, 1H), 7.36 (dd, J = 8.1, 4.7, 1H), 7.21 (d, J = 2.5, 1H), 7.17 (s, 1H, 5.53 (s, 1H), 3.84-3.73 (m, 4H), 3.50-3.41 (m, 4H). 314 (5,6-Dimethyl- pyrazin-2-yl)-[4- fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol C B B MS: 446.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.51 (s, 1H), 7.66-7.61 (m, 2H), 7.54-7.49 (m, 2H), 7.40-7.35 (m, 1H), 7.21-7.19 (m, 1H), 6.32 (d, J = 4.2, 1H), 5.84 (d, J = 4.0, 1H), 3.80- 3.75 (m, 4H), 3.46-3.42 (m, 4H), 2.45 (s, 3H), 2.44 (s, 3H). 315 2-[2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(3-chloro- pyrazin-2-yl)- acetamide D D C MS: 495.0/497.1/499.1 (M + H.sup.+) (Cl.sub.2 isotopy, 1H NMR (500 MHz, DMSO-d6) ppm = 9.07 (s, rel. peak intensity ratio [%] 100:75:20) 1H), 8.60 (d, J = 2.5, 1H), 8.45 (d, J = 2.5, 1H), 7.97- 7.91 (m, 1H), 7.88 (d, J = 9.5, 1H), 7.75 (dd, J = 8.3, 2.1, 1H), 7.71 (d, J = 8.2, 1H), 7.66 (d, J = 2.1, 1H), 7.53 (dd, J = 9.5, 2.6, 1H), 7.47-7.42 (m, 1H), 7.22-7.19 (m, 1H), 5.87 (s, 1H), 3.81- 3.76 (m, 4H), 3.47-3.42 (m, 4H). 316 2-[2-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(3- methoxy-pyrazin-2- yl)acetamide D C B MS: 475.4 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.05 (s, 1H), 8.13 (d, J = 2.9, 2H), 7.94 (d, J = 9.4, 1H), 7.78- 7.70 (m, 3H), 7.53 (dd, J = 9.5, 2.6, 1H), 7.41 (dd, J = 9.6, 8.6, 1H), 7.23 (s, 1H), 7.19 (d, J = 2.5, 1H), 5.59 (s, 1H), 3.95 (s, 3H), 3.82-3.74 (m, 4H), 3.48-3.40 (m, 4H). 317 2-[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(1-methyl- 6-oxo-1,6-dihydro- pyridazin-3-yl)- acetamide D D B MS: 475.3 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 7.86 (s, 1H), 7.64-7.50 (m, 4H), 7.47 (d, J = 9.6, 1H), 7.44 (dd, J = 9.8, 8.5, 1H), 7.34 (s, 1H), 7.20 (d, J = 2.2, 1H), 6.90 (d, J = 9.6, 1H), 5.05 (s, 1H), 3.83-3.73 (m, 4H), 3.61 (s, 3H), 3.44 (t, J = 4.9, 4H). 318 2-(3,5-Dimethyl- pyrazin-2-yl)-2-[4- fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]acetamide C D A MS: 473.4 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.29 (s, 1H), 7.60 (dd, J = 9.5, 2.9, 1H), 7.59- 7.55 (m, 2H), 7.54 (dd, J = 9.5, 2.5, 1H), 7.50 (s, 1H), 7.42-7.33 (m, 1H), 7.20 (d, J = 2.5, 1H), 7.15 (s, 1H), 5.35 (s, 1H), 3.78 (dd, J = 5.8, 4.0, 4H), 3.44 (dd, J = 6.0, 3.9, 4H), 2.49 (s, 3H), 2.41 (s, 3H). 319 0 2-[2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(3- methoxy-pyrazin-2- yl)acetamide C C A MS: 493.4 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, 1H), 8.13 (d, J = 2.8, 1H), 8.11 (d, J = 2.8, 1H), 7.73 (s, 1H), 7.61 (dd, J = 9.4, 3.2, 1H), 7.58-7.46 (m, 3H), 7.24 (s, 1H), 7.20 (d, J = 2.4, 1H), 5.53 (s, 1H), 3.95 (s, 3H), 3.78 (dd, J = 5.8, 4.0, 4H), 3.45 (dd, J = 6.0, 3.9, 4H). 320 2-[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(3- methoxy-pyrazin-2- yl)acetamide C B A MS: 509.3/511.3 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, intensity ratio [%] 100:38) 1H), 8.12 (d, J = 2.8, 1H), 8.09 (d, J = 2.8, 1H), 7.78 (s, 1H), 7.72 (d, J = 9.6, 1H), 7.60 (dd, J = 9.4, 3.1, 1H), 7.55 (dd, J = 9.5, 2.5, 1H), 7.51 (d, J = 7.6, 1H), 7.26 (s, 1H), 7.20 (d, J = 2.4, 1H), 5.65 (s, 1H), 3.95 (s, 3H), 3.86-3.66 (m, 4H), 3.56-3.37 (m, 4H). 321 2-(3,5-Difluoro- pyridin-4-yl)-2-[4- fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]acetamide C B B MS: 480.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.50 (s, 2H), 7.59 (s, 1H), 7.58-7.49 (m, 4H), 7.46-7.37 (m, 2H), 7.20 (d, J = 2.2, 1H), 5.42 (s, 1H), 3.87-3.64 (m, 4H), 3.59-3.40 (m, 4H). 322 2-(4-Chloro-5-fluoro- pyridin-3-yl)-2-[4- fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]acetamide B B C MS: 496.2/498.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (d, intensity ratio [%] 100:37) J = 2.3, 1H), 8.65 (s, 1H), 8.33 (s, 1H), 7.94 (s, 1H), 7.61-7.50 (m, 4H), 7.44 (dt, J = 20.5, 9.0, 2H), 7.20 (d, J = 2.1, 1H), 5.44 (s, 1H), 3.80-3.75 (m, 4H), 3.47-3.42 (m, 4H). 323 2-[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-imidazo- [1,2-b]pyridazin-6-yl- acetamide B B B MS: 518.2/520.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (d, intensity ratio [%] 100:35) J = 10.0, 1H), 8.24 (s, 1H), 8.08 (d, J = 9.5, 1H), 8.02 (s, 1H), 7.79 (d, J = 9.5, 1H), 7.76 (d, J = 1.2, 1H), 7.72 (d, J = 7.6, 1H), 7.60 (dd, J = 9.5, 3.2, 1H), 7.53 (dd, J = 9.5, 2.5, 1H), 7.47 (s, 1H), 7.22 (d, J = 2.5, 1H), 7.11 (d, J = 9.5, 1H), 5.61 (s, 1H), 3.81- 3.74 (m, 4H), 3.49-3.42 (m, 4H). 324 2-[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(3-methyl- pyrazin-2-yl)- acetamide B B A MS: 493.3/495.3 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, intensity ratio [%] 100:38) 1H), 8.40 (d, J = 2.5, 1H), 8.38 (d, J = 2.5, 1H), 7.80 (s, 1H), 7.73 (d, J = 9.5, 1H), 7.59 (dd, J = 9.4, 3.0, 1H), 7.54 (dd, J = 9.5, 2.5, 1H), 7.48 (d, J = 7.6, 1H), 7.34 (s, 1H), 7.19 (d, J = 2.4, 1H), 5.66 (s, 1H), 3.78 (dd, J = 5.8, 4.0, 4H), 3.45 (dd, J = 5.9, 3.9, 4H), 2.55 (s, 3H). 325 2-[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(6- methoxypyridazin-3- yl)acetamide D D B MS: 509.2/511.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, intensity ratio [%] 100:37) 1H), 7.96 (s, 1H), 7.75 (d, J = 9.5, 1H), 7.71 (d, J = 7.6, 1H), 7.63-7.51 (m, 2H), 7.47 (d, J = 9.2, 1H), 7.39 (s, 1H), 7.21 (d, J = 2.4, 1H), 7.17 (d, J = 9.2, 1H), 5.67 (s, 1H), 4.00 (s, 3H), 3.82-3.74 (m, 4H), 3.50-3.42 (m, 4H). 326 6-{[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-2-methyl-2H- pyridazin-3-one C B A MS: 448.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 7.66-7.60 (m, 2H), 7.55-7.49 (m, 2H), 7.47 (d, J = 9.6, 1H), 7.44-7.39 (m, 1H), 7.21- 7.19 (m, 1H), 6.93 (d, J = 9.6, 1H), 6.46 (d, J = 4.3, 1H), 5.66 (d, J = 4.3, 1H), 3.80-3.75 (m, 4H), 3.62 (s, 3H), 3.46-3.42 (m, 4H). 327 2-[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(3-methyl- pyrazin-2-yl)- acetamide C D A MS: 459.3 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.41 (d, J = 2.4, 1H), 8.38 (d, J = 2.6, 1H), 7.64- 7.51 (m, 5H), 7.38 (dd, J = 10.6, 8.5, 1H), 7.21- 7.16 (m, 2H), 5.41 (s, 1H), 3.83-3.74 (m, 4H), 3.46-3.40 (m, 4H), 2.54 (s, 3H). 328 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[2,3-c]- pyridin-7-ylmethanol A A D MS: 457.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, 1H), 8.32 (d, J = 5.2, 1H), 8.21 (d, J = 2.2, 1H), 7.74- 7.67 (m, 2H), 7.64 (d, J = 5.2, 1H), 7.52-7.49 (m, 2H), 7.36 (dd, J = 9.9, 8.4, 1H), 7.22-7.16 (m, 1H), 7.06 (d, J = 2.2, 1H), 6.32 (d, J = 5.0, 1H), 6.25 (d, J = 5.0, 1H), 3.80-3.75 (m, 4H), 3.46-3.41 (m, 4H). 329 0 2-[2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(3-methyl- pyrazin-2-yl)- acetamide C C A MS: 477.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, 1H), 8.41 (d, J = 2.6, 1H), 8.39 (d, J = 2.7, 1H), 7.77- 7.68 (m, 1H), 7.61 (dd, J = 9.4, 3.1, 1H), 7.59- 7.47 (m, 3H), 7.32 (s, 1H), 7.19 (d, J = 2.5, 1H), 5.57 (s, 1H), 3.84-3.74 (m, 4H), 3.48-3.41 (m, 4H), 2.55 (s, 3H). 330 5-Chloro-6-{[2- chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}pyrimidin-4-ol C D A MS: 484.1/486.1/488.1 (M + H.sup.+) (Cl.sub.2 isotopy, rel. 1H NMR (500 MHz, DMSO-d6) ppm = 13 06 (s, peak intensity ratio [%] 100:70:18) 1H), 9.09 (s, 1H), 8.22-8.14 (m, 2H), 7.97 (d, J = 9.4, 1H), 7.71 (dd, J = 8.2, 2.2, 1H), 7.62-7.56 (m, 2H), 7.22 (d, J = 2.6, 1H), 6.46 (d, J = 5.5, 1H), 6.31 (d, J = 5.5, 1H), 3.83-3.77 (m, 4H), 3.48- 3.43 (m, 4H). 331 (3-methyl-pyrazin-2- yl)-[3-(7-morpholin-4- ylquinazolin-4-yl)-4- oxocyclohexa-2,5- dien-(E)-ylidene]- acetic acid C C A MS: 456.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.06 (s, 1H), 8.70 (d, J = 2.5, 1H), 8.56 (d, J = 2.6, 1H), 8.01 (dd, J = 8.8, 2.3, 1H), 7.84 (d, J = 2.3, 1H), 7.48 (d, J = 1.4, 2H), 7.38 (d, J = 8.8, 1H), 7.17-7.14 (m, 1H), 3.81-3.74 (m, 4H), 3.45-3.39 (m, 4H), 2.55 (s, 3H). 332 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thieno[2,3-d}- pyridazin-7-yl- methanol A A B MS: 474.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.56 (s, 1H), 9.08 (s, 1H), 8.26 (d, J = 5.4, 1H), 7.79-7.72 (m, 2H), 7.70 (d, J = 5.4, 1H), 7.51-7.44 (m, 2H), 7.43-7.35 (m, 1H), 7.21-7.16 (m, 1H), 7.10 (d, J = 3.8, 1H), 6.38 (d, J = 3.9, 1H), 3.82-3.74 (m, 4H), 3.47-3.40 (m, 4H). 333 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thieno[2,3-d}- pyridazin-4-yl- methanol A A B MS: 474.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.84 (d, J = 0.6, 1H), 9.08 (s, 1H), 8.28 (d, J = 5.3, 1H), 7.89 (dd, J = 5.4, 0.7, 1H), 7.75-7.67 (m, 2H), 7.49 (dd, J = 9.4, 2.4, 1H), 7.45 (dd, J = 9.4, 2.9, 1H), 7.42- 7.34 (m, 1H), 7.19 (d, J = 2.3, 1H), 6.82 (s, 1H), 6.42 (s, 1H), 3.81-3.75 (m, 4H), 3.47-3.41 (m, 4H). 334 2-[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(1,4- dimethyl-6-oxo-1,6- dihydropyridin-2-yl)- acetamide D D A MS: 522.1/524.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, intensity ratio [%] 100:35) 1H), 8.10-7.99 (m, 1H), 7.85 (d, J = 9.4, 1H), 7.58- 7.49 (m, 3H), 7.34 (d, J = 7.4, 1H), 7.24-7.17 (m, 1H), 6.22-6.15 (m, 1H), 5.79-5.77 (m, 1H), 5.47 (s, 1H), 3.82-3.75 (m, 4H), 3.46 (t, J = 5.0, 4H), 3.36 (s, 3H), 2.05 (s, 3H). 335 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[2,3-d}- pyridazin-7-yl- methanol A A A MS: 458.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.59 (s, 1H), 9.09 (s, 1H), 8.37 (d, J = 2.1, 1H), 7.82-7.70 (m, 2H), 7.54-7.47 (m, 2H), 7.40 (dd, J = 9.8, 8.6, 1H), 7.23-7.16 (m, 2H), 6.69 (d, J = 4.6, 1H), 6.40 (d, J = 4.6, 1H), 3.81-3.75 (m, 4H), 3.47-3.41 (m, 4H). 336 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[2,3-d}- pyridazin-7-yl- methanol A A A MS: 475.7 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.63 (s, 1H), 9.14 (s, 1H), 8.41 (d, J = 2.1, 1H), 8.10 (t, J = 8.1, 1H), 7.63 (dd, J = 9.4, 3.0, 1H), 7.58 (dd, J = 9.4, 2.5, 1H), 7.45 (t, J = 10.1, 1H), 7.27-7.19 (m, 2H), 6.82 (d, J = 5.3, 1H), 6.63 (d, J = 5.3, 1H), 3.83-3.77 (m, 4H), 3.50-3.45 (m, 4H). 337 7-[[4-Fluoro-3-(7- morpholino- quinazolin-4-yl)- phenyl]hydroxy- methyl]-5H-thieno- [2,3-d}pyridazin-4- one A B B MS: 490.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 12.73 (s, 1H), 9.10 (s, 1H), 8.04 (d, J = 5.3, 1H), 7.74-7.63 (m, 2H), 7.59 (d, J = 5.2, 1H), 7.53-7.45 (m, 2H), 7.44-7.37 (m, 1H), 7.23-7.13 (m, 1H), 6.88 (s, 1H), 5.94 (s, 1H), 3.82-3.71 (m, 4H), 3.46-3.41 (m, 4H). 338 4-[[4-Fluoro-3-(7- morpholino- quinazolin-4-yl)- phenyl]hydroxy- methyl]-6H- thieno[2,3-d}- pyridazin-7-one A B A MS: 490.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 12.82 (s, 1H), 9.09 (s, 1H), 8.18 (d, J = 5.2, 1H), 7.70-7.64 (m, 2H), 7.62 (d, J = 5.2, 1H), 7.50 (dd, J = 9.4, 2.4, 1H), 7.47 (dd, J = 9.4, 2.8, 1H), 7.44-7.36 (m, 1H), 7.19 (d, J = 2.3, 1H), 6.62 (s, 1H), 6.01 (s, 1H), 3.81-3.73 (m, 4H), 3.48-3.40 (m, 4H). 339 0 6-{[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1,4-dimethyl- 1H-pyridin-2-one C B A MS: 494.7/496.7 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.13 (s, intensity ratio [%] 100:37) 1H), 7.79 (d, J = 9.5, 1H), 7.71 (d, J = 7.6, 1H), 7.60 (dd, J = 9.4, 3.2, 1H), 7.54 (dd, J = 9.4, 2.5, 1H), 7.22 (d, J = 2.4, 1H), 6.60 (d, J = 6.2, 1H), 6.27- 6.15 (m, 1H), 6.05 (d, J = 6.2, 1H), 5.84-5.68 (m, 1H), 3.81-3.75 (m, 4H), 3.52-3.43 (m, 7H), 2.05 (s, 3H). 340 6-{[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1,4-dimethyl- 1H-pyridin-2-one A B A MS: 461.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 7.62-7.54 (m, 2H), 7.54-7.49 (m, 2H), 7.49-7.41 (m, 1H), 7.22-7.18 (m, 1H), 6.50 (d, J = 5.1, 1H), 6.21-6.15 (m, 2H), 5.90 (d, J = 5.1, 1H), 3.81-3.74 (m, 4H), 3.48-3.41 (m, 4H), 3.30 (s, 3H), 2.12 (s, 3H). 341 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thieno[2,3-d}- pyridazin-4-yl- methanol A A B MS: 492.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.85 (d, J = 0.8, 1H), 9.12 (s, 1H), 8.33 (d, J = 5.3, 1H), 8.01 (t, J = 8.1, 1H), 7.91 (dd, J = 5.4, 0.8, 1H), 7.66- 7.50 (m, 2H), 7.43 (t, J = 10.1, 1H), 7.21 (d, J = 2.4, 1H), 6.84 (s, 1H), 6.63 (s, 1H), 3.86-3.70 (m, 4H), 3.54-3.40 (m, 4H). 342 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thieno[2,3-d}- pyridazin-7-yl- methanol A A A MS: 492.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.57 (s, 1H), 9.09 (s, 1H), 8.27 (d, J = 5.4, 1H), 7.86 (t, J = 8.0, 1H), 7.71 (d, J = 5.4, 1H), 7.61-7.42 (m, 3H), 7.19 (d, J = 2.4, 1H), 7.16 (d, J = 4.8, 1H), 6.54 (d, J = 4.8, 1H), 3.85-3.69 (m, 4H), 3.50-3.38 (m, 4H). 343 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-[1,2,4]- triazolo[4,3-a]pyridin- 3-ylmethanol (Ena 2) A B B MS: 457.2 (M + H.sup.+); R.sub.t 11.36 min (SFC, see racemate Chiralpak AS-H, CO.sub.2/20% by vol. of methanol, 0.5% by vol. of diethylamine) 344 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-[1,2,4]- triazolo[4,3-a]pyridin- 3-ylmethanol (Ena 1) A C A MS: 457.2 (M + H.sup.+); R.sub.t 8.65 min (SFC, Chiralpak see racemate AS-H, CO.sub.2/20% by vol. of methanol, 0.5% by vol. of diethylamine) 345 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]pyrrolo[2,1-f]- [1,2,4]triazin-4-yl- methanol A A D MS: 457.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.49 (s, 1H), 8.08 (dd, J = 2.6, 1.4, 1H), 7.84- 7.76 (m, 2H), 7.53-7.45 (m, 2H), 7.42-7.36 (m, 1H), 7.29 (dd, J = 4.6, 1.4, 1H), 7.19 (d, J = 2.0, 1H), 7.02 (dd, J = 4.6, 2.6, 1H), 6.62 (s, 1H), 6.07 (s, 1H), 3.80-3.74 (m, 4H), 3.46-3.41 (m, 4H). 346 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(9-methyl- 9H-purin-6-yl)- methanol (Ena 2) C D B MS: 490.2 (M + H.sup.+); R.sub.t 7.65 min (SFC, Chiralpak see racemate AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 347 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(9-methyl- 9H-purin-6-yl)- methanol (Ena 1) B B A MS: 490.2 (M + H.sup.+); R.sub.t 4.59 min (SFC, Chiralpak see racemate AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 348 2-[2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-pyrrolo- [1,2-a]pyrazin-1-yl- acetamide A B C MS: 501.3 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 8.23-8.19 (m, 1H), 7.93 (s, 1H), 7.80 (t, J = 8.2, 1H), 7.77 (dd, J = 2.4, 1.4, 1H), 7.63 (dd, J = 9.4, 3.1, 1H), 7.55 (dd, J = 12.3, 2.8, 1H), 7.50 (d, J = 10.0, 1H), 7.44 (d, J = 4.8, 1H), 7.33 (s, 1H), 7.21 (d, J = 2.5, 1H), 6.94-6.89 (m, 2H), 5.75 (s, 1H), 3.82-3.77 (m, 4H), 3.49-3.45 (m, 4H). 349 00 4-[2-Fluoro-5-(3- methyl-pyrazin-2- ylmethyl)phenyl]-7- morpholin-4-yl- quinazoline B A A MS: 416.3 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.43-8.36 (m, 2H), 7.56-7.49 (m, 2H), 7.46 (dd, J = 7.8, 5.5, 2H), 7.39-7.33 (m, 1H), 7.22-7.16 (m, 1H), 4.28 (s, 2H), 3.81-3.75 (m, 4H), 3.46-3.41 (m, 4H), 2.53 (s, 3H). 350 01 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-[1,2,4]- triazolo[4,3-a]pyridin- 5-ylmethanol B C A MS: 475.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.33 (s, 1H), 9.13 (s, 1H), 7.94 (t, J = 8.1, 1H), 7.80 (d, J = 9.2, 1H), 7.61-7.50 (m, 3H), 7.42 (dd, J = 9.2, 6.8, 1H), 7.22 (d, J = 2.4, 1H), 6.93 (d, J = 5.7, 1H), 6.87 (d, J = 6.8, 1H), 6.49 (d, J = 5.6, 1H), 3.83- 3.75 (m, 4H), 3.49-3.43 (m, 4H). 351 02 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-[1,2,4]- triazolo[4,3-a]- pyrazin-8-ylmethanol C D A MS: 458.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.44 (s, 1H), 9.09 (s, 1H), 8.52 (d, J = 4.7, 1H), 7.91 (d, J = 4.7, 1H), 7.85-7.78 (m, 2H), 7.53 (dd, J = 9.4, 2.9, 1H), 7.50 (dd, J = 9.4, 2.4, 1H), 7.41-7.35 (m, 1H), 7.20 (d, J = 2.3, 1H), 6.51 (s, 1H), 6.43 (s, 1H), 3.82-3.74 (m, 4H), 3.47-3.41 (m, 4H). 352 03 4-{2-Fluoro-5- [methoxy-(3-methyl- pyrazin-2-yl)methyl]- phenyl}-7-morpholin- 4-ylquinazoline (Ena 1) D A* MS: 446.2 (M + H.sup.+); R.sub.t 3.08 min (SFC, Chiralcel 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, OJ-H, CO.sub.2/20% by vol. of 2-propanol, 0.5% by 1H), 8.53-8.42 (m, 2H), 7.69-7.58 (m, 2H), vol. of diethylamine) 7.58-7.48 (m, 2H), 7.48-7.38 (m, 1H), 7.21 (d, J = 1.9, 1H), 5.80 (s, 1H), 3.81-3.70 (m, 4H), 3.48- 3.39 (m, 4H), 3.36 (s, 3H), 2.59 (s, 3H). 353 04 4-{2-Fluoro-5- [methoxy-(3-methyl- pyrazin-2-yl)methyl]- phenyl}-7-morpholin- 4-ylquinazoline (Ena 2) C D A MS: 446.2 (M + H.sup.+); R.sub.t 3.78 min (SFC, Chiralcel 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, OJ-H, CO.sub.2/20% by vol. of 2-propanol, 0.5% by 1H), 8.52-8.43 (m, 2H), 7.69-7.58 (m, 2H), vol. of diethylamine) 7.58-7.51 (m, 2H), 7.49-7.39 (m, 1H), 7.28- 7.15 (m, 1H), 5.81 (s, 1H), 3.84-3.74 (m, 4H), 3.49-3.42 (m, 4H), 3.36 (s, 3H, 2.59 (s, 3H). 354 05 (3,5-Dimethyl- pyrazin-2-yl)-[4- fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol A A A MS: 446.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.30 (s, 1H), 7.60-7.50 (m, 4H), 7.41-7.33 (m, 1H), 7.23-7.17 (m, 1H), 6.20 (d, J = 5.4, 1H), 6.04 (d, J = 5.2, 1H), 3.81-3.76 (m, 4H), 3.47- 3.42 (m, 4H), 2.50 (s, 3H), 2.43 (s, 3H). 355 06 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3,5- dimethyl-pyrazin-2- yl)methanol B B B MS: 464.3 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, 1H), 8.26 (s, 1H), 7.89 (t, J = 8.2, 1H), 7.61 (dd, J = 9.4, 3.2, 1H), 7.56 (dd, J = 9.4, 2.5, 1H), 7.39 (t, J = 10.1, 1H), 7.21 (d, J = 2.4, 1H), 6.28 (d, J = 6.0, 1H), 6.23 (d, J = 6.0, 1H), 3.82-3.75 (m, 4H), 3.49- 3.41 (m, 4H), 2.62 (s, 3H), 2.43 (s, 3H). 356 07 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]pyrrolo[1,2-a]- pyrazin-1-ylmethanol A A D MS: 456.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 8.20 (dd, J = 4.8, 1.0, 1H), 7.79-7.72 (m, 3H), 7.53-7.45 (m, 3H), 7.40-7.34 (m, 1H), 7.20 (d, J = 2.1, 1H), 7.02 (dt, J = 4.1, 1.2, 1H), 6.87 (dd, J = 4.1, 2.5, 1H), 6.33 (d, J = 4.9, 1H), 6.06 (d, J = 4.8, 1H), 3.82-3.76 (m, 4H), 3.48-3.42 (m, 4H). 357 08 [2-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6-methoxy- pyridazin-3-yl)- methanol B B A MS: 448.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, 1H), 8.00 (dd, J = 7.1, 2.3, 1H), 7.89 (d, J = 9.4, 1H), 7.80-7.71 (m, 2H), 7.55 (dd, J = 9.5, 2.6, 1H), 7.38 (dd, J = 10.0, 8.4, 1H), 7.27-7.18 (m, 2H), 6.57 (d, J = 4.8, 1H), 6.24 (d, J = 4.8, 1H), 4.01 (s, 3H), 3.85-3.71 (m, 4H), 3.51-3.40 (m, 4H). 358 09 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]pyrrolo[1,2-a]- pyrazin-1-ylmethanol A A C MS: 474.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, 1H), 8.25-8.19 (m, 1H), 7.94 (t, J = 8.2, 1H), 7.78 (dd, J = 2.5, 1.3, 1H), 7.58 (dd, J = 9.3, 3.0, 1H), 7.55 (dd, J = 9.4, 2.4, 1H), 7.47-7.39 (m, 2H), 7.22 (d, J = 2.3, 1H), 6.97-6.93 (m, 1H), 6.91 (dd, J = 4.1, 2.5, 1H), 6.43 (d, J = 5.9, 1H), 6.30 (d, J = 5.9, 1H), 3.82-3.76 (m, 4H), 3.49-3.44 (m, 4H). 359 0 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]pyrrolo[1,2-a]- pyrazin-1-ylmethanol A A D MS: 490.2/492.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, intensity ratio [%] 100:31) 1H), 8.20 (dd, J = 4.7, 1.0, 1H), 7.97 (d, J = 7.8, 1H), 7.76 (dd, J = 2.5, 1.3, 1H), 7.63 (d, J = 9.5, 1H), 7.60 (dd, J = 9.4, 3.2, 1H), 7.55 (dd, J = 9.4, 2.6, 1H), 7.40 (d, J = 4.8, 1H), 7.21 (d, J = 2.5, 1H), 7.00- 6.95 (m, 1H), 6.91 (dd, J = 4.1, 2.5, 1H), 6.48 (d, J = 6.2, 1H), 6.36 (d, J = 6.1, 1H), 3.81-3.75 (m, 4H), 3.48-3.43 (m, 4H). 360 2-{[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-3-methyl-3H- pyrimidin-4-one B B A MS: 448.3 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 7.91 (d, J = 6.5, 1H), 7.67-7.60 (m, 2H), 7.60- 7.50 (m, 2H), 7.44 (t, J = 9.5, 1H), 7.20 (d, J = 1.7, 1H), 6.72 (s, 1H), 6.38 (d, J = 6.5, 1H), 6.00 (s, 1H), 3.82-3.73 (m, 4H), 3.48 (s, 3H), 3.47-3.42 (m, 4H). 361 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]pyrrolo[1,2-a]- pyrazin-1-ylmethanol B B D MS: 472.2/474.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, intensity ratio [%] 100:33) 1H), 8.22-8.19 (m, 1H), 8.14 (d, J = 2.2, 1H), 7.89 (d, J = 9.4, 1H), 7.76 (dd, J = 2.5, 1.3, 1H), 7.70 (dd, J = 8.2, 2.2, 1H), 7.61 (d, J = 8.2, 1H), 7.53 (dd, J = 9.5, 2.6, 1H), 7.43 (d, J = 4.8, 1H), 7.21 (d, J = 2.6, 1H), 7.00-6.97 (m, 1H), 6.93-6.90 (m, 1H), 6.45-6.40 (m, 2H), 3.81-3.76 (m, 4H), 3.48-3.42 (m, 4H). 362 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]pyrrolo[2,1-f]- [1,2,4]triazin-4-yl- methanol B B D MS: 473.2/475.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, intensity ratio [%] 100:38) 1H), 8.49 (s, 1H), 8.16 (d, J = 2.2, 1H), 8.12 (dd, J = 2.6, 1.4, 1H), 7.88 (d, J = 9.4, 1H), 7.74 (dd, J = 8.2, 2.2, 1H), 7.64 (d, J = 8.2, 1H), 7.54 (dd, J = 9.5, 2.6, 1H), 7.23-7.19 (m, 2H), 7.06 (dd, J = 4.6, 2.6, 1H), 6.80 (d, J = 5.7, 1H), 6.44 (d, J = 5.7, 1H), 3.81-3.76 (m, 4H), 3.48-3.43 (m, 4H). 363 6-{[2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1-methyl-1H- pyridin-2-one (Ena 2) C C B MS: 463.2/465.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:42); R.sub.t 4.63 min (SFC, Chiralcel OJ-H, CO.sub.2/20% by vol. of methanol, 0.5% by vol. of diethylamine) 364 6-{[2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1-methyl-1H- pyridin-2-one (Ena 1) A A A MS: 463.2/465.2 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:41); R.sub.t 2.74 min (SFC, Chiralcel OJ-H, CO.sub.2/20% by vol. of methanol, 0.5% by vol. of diethylamine) 365 6-{[2-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1-methyl-1H- pyridin-2-one (Ena 2) B B A MS: 447.2 (M + H.sup.+); R.sub.t 7.64 min (SFC, Chiralpak see racemate AS-H, CO.sub.2/25% by vol. of methanol) 366 6-{[2-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1-methyl-1H- pyridin-2-one (Ena 1) C C A MS: 447.2 (M + H.sup.+); R.sub.t 4.61 min (SFC, Chiralpak see racemate AS-H, CO.sub.2/25% by vol. of methanol) 367 6-{[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-2H- pyridazin-3-one (Ena 1) A B A MS: 434.1 (M + H.sup.+); Rt 13.79 min, (SFC, see enantiomer Chiralcel OJ-H, OJ-H, CO.sub.2/15% by vol. of methanol, 0.5% by vol. of diethylamine) Ena 2 to this compound: Example 76 368 2-{[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-3-methyl-3H- pyrimidin-4-one C C A MS: 482.2/484.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.14 (s, intensity ratio [%] 100:41) 1H), 7.88 (d, J = 7.7, 1H), 7.83 (d, J = 6.5, 1H), 7.70 (d, J = 9.4, 1H), 7.63 (dd, J = 9.4, 3.2, 1H), 7.57 (dd, J = 9.5, 2.5, 1H), 7.23 (d, J = 2.4, 1H), 6.91 (d, J = 7.0, J = 7.0, 1H), 6.39 (d, J = 6.5, 1H), 6.15 (d, 1H), 3.83-3.76 (m, 4H), 3.72 (s, 3H), 3.50-3.44 (m, 4H). 369 0 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]imidazo- [1,2-a]pyrazin-8-yl- methanol C C B MS: 473.1/475.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, intensity ratio [%] 100:25) 1H), 8.57 (d, J = 4.5, 1H), 8.27 (d, J = 2.2, 1H), 8.18 (d, J = 1.1, 1H), 8.04 (d, J = 9.4, 1H), 7.88 (d, J = 1.1, 1H), 7.83 (d, J = 4.5, 1H), 7.72 (dd, J = 8.2, 2.3, 1H), 7.62-7.55 (m, 2H), 7.23 (d, J = 2.6, 1H), 6.87 (d, J = 5.8, 1H), 6.50 (d, J = 5.9, 1H), 3.83-3.78 (m, 4H), 3.50-3.45 (m, 4H). 370 [2-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(9-methyl- 9H-purin-6-yl)- methanol C B A MS: 472.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.07 (s, 1H), 8.91 (s, 1H), 8.58 (s, 1H), 8.28 (dd, J = 7.0, 2.3, 1H), 8.05 (d, J = 9.4, 1H), 7.72 (ddd, J = 8.3, 5.0, 2.4, 1H), 7.58 (dd, J = 9.5, 2.6, 1H), 7.30 (dd, J = 10.0, 8.5, 1H), 7.21 (d, J = 2.5, 1H), 6.66 (d, J = 5.5, 1H), 6.44 (d, J = 5.6, 1H), 3.85 (s, 3H), 3.82- 3.78 (m, 4H), 3.49-3.45 (m, 4H). 371 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(9-methyl- 9H-purin-6-yl)- methanol C B C MS: 488.2/490.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, intensity ratio [%] 100:33) 1H), 8.90 (s, 1H), 8.59 (s, 1H), 8.38 (d, J = 2.2, 1H), 8.12 (d, J = 9.4, 1H), 7.70 (dd, J = 8.2, 2.3, 1H), 7.60 (dd, J = 9.5, 2.6, 1H), 7.56 (d, J = 8.2, 1H), 7.23 (d, J = 2.6, 1H), 6.71 (d, J = 5.4, 1H), 6.53 (d, J = 5.4, 1H), 3.86 (s, 3H), 3.82-3.77 (m, 4H), 3.49-3.45 (m, 4H). 372 [2-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]imidazo- [1,2-a]pyrazin-8-yl- methanol C B A MS: 457.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, 1H), 8.58 (d, J = 4.5, 1H), 8.24-8.16 (m, 2H), 8.00 (d, J = 9.4, 1H), 7.91-7.83 (m, 2H), 7.74 (ddd, J = 8.1, 5.0, 2.4, 1H), 7.57 (dd, J = 9.5, 2.6, 1H), 7.33 (dd, J = 10.0, 8.5, 1H), 7.22 (d, J = 2.5, 1H), 6.80 (d, J = 5.9, 1H), 6.39 (d, J = 6.0, 1H), 3.86- 3.75 (m, 4H), 3.52-3.43 (m, 4H). 373 [2-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-[1,2,4]- triazolo[4,3-a]pyridin- 5-ylmethanol B B B MS: 457.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.36-9.30 (m, 1H), 9.07 (s, 1H), 8.03 (dd, J = 7.2, 2.3, 1H), 7.86-7.76 (m, 3H), 7.52-7.38 (m, 3H), 7.21 (d, J = 2.6, 1H), 6.91 (d, J = 5.6, 1H), 6.87-6.80 (m, 1H), 6.53 (d, J = 5.6, 1H), 3.83-3.74 (m, 4H), 3.48- 3.40 (m, 4H). 374 [2-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[3,2-d}- pyrimidin-4-yl- methanol A B B MS: 458.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, 1H), 9.02 (s, 1H), 8.59 (d, J = 2.2, 1H), 8.20 (dd, J = 7.0, 2.3, 1H), 7.92 (d, J = 9.4, 1H), 7.77 (ddd, J = 8.4, 5.0, 2.4, 1H), 7.57 (dd, J = 9.5, 2.6, 1H), 7.37 (dd, J = 10.0, 8.5, 1H), 7.27 (d, J = 2.3, 1H), 7.22 (d, J = 2.5, 1H), 6.73 (d, J = 5.2, 1H), 6.48 (d, J = 5.1, 1H), 3.82-3.76 (m, 4H), 3.49-3.44 (m, 4H). 375 6-{[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1-methyl-1H- pyridin-2-one (Ena 2) A B A MS: 447.3 (M + H.sup.+); R.sub.t 4.15 min (SFC, Chiralcel see racemate OJ-H, CO.sub.2/20% by vol. of methanol, 0.5% by vol. of diethylamine) 376 6-{[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1-methyl-1H- pyridin-2-one (Ena 1) A A A MS: 447.3 (M + H.sup.+); R.sub.t 3.23 min (SFC, Chiralcel see racemate OJ-H, CO.sub.2/20% by vol. of methanol, 0.5% by vol. of diethylamine) 377 2-[2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(5-methyl- pyrimidin-4-yl)- acetamide (Ena 2) B B B MS: 475.1/477.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:34); R.sub.t 6.14 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 378 2-[2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(5-methyl- pyrimidin-4-yl)- acetamide (Ena 1) B B A MS: 475.1/477.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:34); R.sub.t 3.81 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 379 0 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-[1,2,4]- triazolo[4,3-a]pyridin- 3-ylmethanol B B A MS: 475.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.14 (s, 1H), 8.63 (dt, J = 7.1, 1.2, 1H), 8.02 (t, J = 8.1, 1H), 7.81 (dt, J = 9.3, 1.1, 1H), 7.64 (dd, J = 9.4, 3.3, 1H), 7.60-7.50 (m, 2H), 7.44 (ddd, J = 9.3, 6.6, 1.1, 1H), 7.23 (d, J = 2.5, 1H), 7.06 (td, J = 6.8, 1.0, 1H), 6.87 (d, J = 6.0, 1H), 6.69 (d, J = 6.0, 1H), 3.82- 3.77 (m, 4H), 3.49-3.45 (m, 4H). 380 6-{[2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1-methyl-1H- pyridin-2-one (Ena 2) B B A MS: 465.2 (M + H.sup.+); R.sub.t 10.95 min (SFC, see racemate Chiralpak AD-H, CO.sub.2/20% by vol. of methanol, 0.5% by vol. of diethylamine) 381 6-{[2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1-methyl-1H- pyridin-2-one (Ena 1) A B A MS: 465.2 (M + H.sup.+); R.sub.t 7.49 min (SFC, Chiralpak see racemate AD-H, CO.sub.2/20% by vol. of methanol, 0.5% by vol. of diethylamine) 382 6-{[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1-methyl-1H- pyridin-2-one (Ena 2) C B B MS: 481.1/483.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:35); R.sub.t 4.55 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 383 6-{[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1-methyl-1H- pyridin-2-one (Ena 1) A A A MS: 481.1/483.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:35); R.sub.t 2.24 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 384 (R)-[2,4-Difluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(7-methyl- 7H-purin-6-yl)- methanol (Ena 2) C D A MS: 490.2 (M + H.sup.+); R.sub.t 5.77 min (SFC, Chiralpak see racemate AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 385 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(1-methyl- 1H-pyrazolo[3,4-d}- pyrimidin-4-yl)- methanol C B A MS: 488.2/490.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.05 (s, intensity ratio [%] 100:31) 1H), 8.92 (s, 1H), 8.44 (s, 1H), 7.95 (d, J = 2.2, 1H), 7.80 (d, J = 9.4, 1H), 7.72 (dd, J = 8.2, 2.2, 1H), 7.66 (d, J = 8.2, 1H), 7.50 (dd, J = 9.5, 2.6, 1H), 7.19 (d, J = 2.5, 1H), 6.90 (d, J = 4.9, 1H), 6.49 (d, J = 4.9, 1H), 4.05 (s, 3H), 3.82-3.76 (m, 4H), 3.47-3.41 (m, 4H). 386 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(7-methyl- 7H-purin-6-yl)- methanol (Ena 1) B C A MS: 490.2 (M + H.sup.+); R.sub.t 3.50 min (SFC, Chiralpak see racemate AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 387 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(5,6,7,8- tetrahydropyrido- [3,4-d}pyrimidin-4-yl)- methanol C B B MS: 491.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 8.83 (s, 1H), 7.87 (t, J = 8.2, 1H), 7.60 (dd, J = 9.4, 3.0, 1H), 7.56 (dd, J = 9.4, 2.5, 1H), 7.42 (t, J = 10.1, 1H), 7.21 (d, J = 2.4, 1H), 6.33 (d, J = 6.3, 1H), 6.16 (d, J = 6.3, 1H), 3.86 (s, 2H), 3.82-3.75 (m, 4H), 3.49-3.42 (m, 4H), 3.09-2.94 (m, 2H), 2.94-2.72 (m, 2H). 388 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(5,6,7,8- tetrahydropyrido- [3,4-d}pyrimidin-4-yl)- methanol C B C MS: 473.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.88 (s, 1H), 7.64-7.56 (m, 2H), 7.55-7.50 (m, 2H), 7.38 (dd, J = 10.5, 8.1, 1H), 7.23-7.16 (m, 1H), 6.20 (d, J = 5.8, 1H), 5.96 (d, J = 5.8, 1H), 3.83 (s, 2H), 3.81-3.72 (m, 4H), 3.49-3.39 (m, 4H), 3.05-2.84 (m, 2H), 2.77-2.72 (m, 2H). 389 0 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(5-fluoro- pyrimidin-4-yl)- methanol (Ena 2) C C C MS: 452.1/454.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:34); R.sub.t 3.98 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 390 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(5-fluoro- pyrimidin-4-yl)- methanol (Ena 1) B B B MS: 452.1/454.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:34); R.sub.t 2.20 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 391 [2-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(1-methyl- 1H-pyrazolo[3,4-d}- pyrimidin-4-yl)- methanol C B B MS: 472.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.05 (s, 1H), 8.90 (s, 1H), 8.49 (s, 1H), 7.93 (dd, J = 6.9, 2.3, 1H), 7.81 (d, J = 9.4, 1H), 7.74 (ddd, J = 8.4, 4.9, 2.3, 1H), 7.52 (dd, J = 9.5, 2.6, 1H), 7.40 (dd, J = 9.9, 8.5, 1H), 7.19 (d, J = 2.6, 1H), 6.88 (s, 1H), 6.37 (s, 1H), 4.05 (s, 3H), 3.81-3.75 (m, 4H), 3.51-3.42 (m, 4H). 392 [2-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(5-methyl- pyrimidin-4-yl)- methanol B B B MS: 432.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, 1H), 8.98 (s, 1H), 8.64 (s, 1H), 8.07 (dd, J = 7.1, 2.3, 1H), 7.93 (d, J = 9.4, 1H), 7.74 (ddd, J = 8.3, 5.0, 2.3, 1H), 7.57 (dd, J = 9.5, 2.6, 1H), 7.35 (dd, J = 10.1, 8.4, 1H), 7.21 (d, J = 2.6, 1H), 6.38 (d, J = 6.0, 1H), 6.25 (d, J = 6.0, 1H), 3.82-3.76 (m, 4H), 3.51-3.43 (m, 4H), 2.41 (s, 3H). 393 [2-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)- methanol B C B MS: 432.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, 1H), 8.45 (d, J = 2.5, 1H), 8.41 (d, J = 2.5, 1H), 8.09 (dd, J = 7.1, 2.3, 1H), 7.94 (d, J = 9.4, 1H), 7.74 (ddd, J = 7.9, 5.0, 2.3, 1H), 7.56 (dd, J = 9.5, 2.6, 1H), 7.33 (dd, J = 10.1, 8.4, 1H), 7.21 (d, J = 2.5, 1H), 6.35 (d, J = 5.8, 1H), 6.32 (d, J = 5.9, 1H), 3.83- 3.76 (m, 4H), 3.45 (t, J = 4.9, 4H), 2.68 (s, 3H). 394 [2-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol B B D MS: 448.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, 1H), 8.19 (d, J = 2.7, 1H), 8.17 (d, J = 2.7, 1H), 8.07 (dd, J = 7.1, 2.3, 1H), 7.93 (d, J = 9.4, 1H), 7.73 (ddd, J = 8.3, 5.0, 2.4, 1H), 7.57 (dd, J = 9.5, 2.6, 1H), 7.33 (dd, J = 10.1, 8.4, 1H), 7.22 (d, J = 2.5, 1H), 6.35 (d, J = 6.0, 1H), 6.21 (d, J = 6.0, 1H), 3.98 (s, 3H), 3.82-3.76 (m, 4H), 3.46 (dd, J = 5.9, 3.9, 4H). 395 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]imidazo- [1,2-a]pyrazin-8-yl- methanol (Ena 2) C C B MS: 491.2/493.2 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:37); R.sub.t 14.57 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 396 (S)-[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]imidazo- [1,2-a]pyrazin-8-yl- methanol (Ena 1) B A A MS: 491.2/493.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:35); R.sub.t 4.27 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 397 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]imidazo- [1,2-a]pyrazin-8-yl- methanol B A A MS: 491.2/493.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.13 (s, intensity ratio [%] 100:35) 1H), 8.55 (d, J = 4.5, 1H), 8.17 (d, J = 1.1, 1H), 8.06 (d, J = 7.8, 1H), 7.85 (d, J = 1.1, 1H), 7.80 (d, J = 4.5, 1H), 7.67 (dd, J = 9.4, 3.1, 1H), 7.61 (d, J = 9.5, 1H), 7.57 (dd, J = 9.5, 2.6, 1H), 7.22 (d, J = 2.5, 1H), 6.81 (d, J = 5.3, 1H), 6.52 (d, J = 6.1, 1H), 3.81-3.77 (m, 4H), 3.49-3.45 (m, 4H). 398 1-Ethyl-6-{[4-fluoro- 3-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1H-pyridin-2- one B B A MS: 461.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 7.63-7.56 (m, 2H), 7.54 (dd, J = 9.4, 2.5, 1H), 7.52-7.43 (m, 2H), 7.41 (dd, J = 9.1, 6.9, 1H), 7.20 (d, J = 2.4, 1H), 6.58 (d, J = 5.0, 1H), 6.35 (dd, J = 9.1, 1.4, 1H), 6.31 (dd, J = 7.0, 1.4, 1H), 5.91 (d, J = 5.0, 1H), 4.05-3.88 (m, 2H), 3.81-3.74 (m, 4H), 3.48-3.39 (m, 4H), 0.95 (t, J = 6.9, 3H). 399 0 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-[1,2,4]- triazolo[4,3-a]pyridin- 3-ylmethanol A B A MS: 457.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 8.51-8.39 (m, 1H), 7.83-7.74 (m, 1H), 7.74-7.64 (m, 2H), 7.55 (dd, J = 9.4, 3.0, 1H), 7.51 (dd, J = 9.4, 2.4, 1H), 7.48-7.42 (m, 1H), 7.42-7.35 (m, 1H), 7.20 (d, J = 2.3, 1H), 7.04- 6.94 (m, 1H), 6.83 (d, J = 5.2, 1H), 6.52 (d, J = 4.8, 1H), 3.88-3.72 (m, 4H), 3.49-3.37 (m, 4H). 400 6-{[2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1-methyl-1H- pyridin-2-one A A B MS: 463.1/465.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, intensity ratio [%] 100:37) 1H), 7.90 (d, J = 2.1, 1H), 7.84 (d, J = 9.4, 1H), 7.79 (dd, J = 8.2, 2.2, 1H), 7.72 (d, J = 8.2, 1H), 7.51 (dd, J = 9.5, 2.6, 1H), 7.33 (dd, J = 9.1, 7.0, 1H), 7.21 (d, J = 2.5, 1H), 6.60 (d, J = 6.2, 1H), 6.38 (dd, J = 9.1, 1.3, 1H), 6.10 (d, J = 6.1, 1H), 5.88 (dd, J = 7.0, 1.4, 1H), 3.84-3.74 (m, 4H), 3.56 (s, 3H), 3.48-3.40 (m, 4H). 401 6-{[2-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1-methyl-1H- pyridin-2-one B B C MS: 447.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.06 (s, 1H), 7.85-7.75 (m, 3H), 7.51 (dd, J = 9.5, 2.6, 1H), 7.46 (dd, J = 10.1, 8.4, 1H), 7.38 (dd, J = 9.1, 7.0, 1H), 7.20 (d, J = 2.5, 1H), 6.59 (d, J = 5.9, 1H), 6.38 (dd, J = 9.1, 1.1, 1H), 6.21-6.15 (m, 1H), 6.14 (d, J = 5.8, 1H), 3.81-3.74 (m, 4H), 3.46 (s, 3H), 3.45- 3.41 (m, 4H). 402 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(1-methyl- 1H-pyrazolo[3,4-d}- pyrimidin-4-yl)- methanol B B B MS: 506.2/508.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, intensity ratio [%] 100:38) 1H), 8.90 (s, 1H), 8.44 (s, 1H), 7.81 (d, J = 7.6, 1H), 7.69 (d, J = 9.5, 1H), 7.56-7.48 (m, 2H), 7.22- 7.16 (m, 1H), 6.92 (d, J = 5.0, 1H), 6.43 (d, J = 5.0, 1H), 4.04 (s, 3H), 3.81-3.74 (m, 4H), 3.48-3.40 (m, 4H). 403 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(1-methyl- 1H-pyrazolo[3,4-d}- pyrimidin-4-yl)- methanol B B B MS: 490.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.07 (s, 1H), 8.89 (s, 1H), 8.49 (s, 1H), 7.79 (t, J = 8.0, 1H), 7.56-7.50 (m, 2H), 7.47 (t, J = 10.0, 1H), 7.19 (s, 1H), 6.88 (s, 1H), 6.32 (s, 1H), 4.04 (s, 3H), 3.81-3.74 (m, 4H), 3.48-3.40 (m, 4H). 404 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(1-methyl- 1H-pyrazolo[3,4-d}- pyrimidin-4-yl)- methanol B A A MS: 472.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.91 (s, 1H), 8.53 (s, 1H), 7.79-7.72 (m, 2H), 7.54-7.44 (m, 2H), 7.38 (dd, J = 9.8, 8.4, 1H), 7.19 (d, J = 2.1, 1H), 6.79 (d, J = 4.0, 1H), 6.10 (d, J = 3.3, 1H), 4.03 (s, 3H), 3.80-3.75 (m, 4H), 3.46- 3.41 (m, 4H). 405 [2-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thieno[3,2-d}- pyrimidin-4-yl- methanol A A D MS: 474.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.07 (s, 1H), 9.04 (s, 1H), 8.49 (d, J = 5.5, 1H), 7.91 (dd, J = 6.9, 2.3, 1H), 7.80 (d, J = 9.4, 1H), 7.79-7.74 (m, 1H), 7.63 (d, J = 5.5, 1H), 7.49 (dd, J = 9.5, 2.6, 1H), 7.43 (dd, J = 9.9, 8.5, 1H), 7.21-7.15 (m, 2H), 6.38 (d, J = 2.1, 1H), 3.83-3.76 (m, 4H), 3.47- 3.42 (m, 4H). 406 [2-Fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thieno[2,3-d}- pyrimidin-4-yl- methanol A A C MS: 474.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.06 (s, 1H), 9.03 (s, 1H), 8.48 (d, J = 5.6, 1H), 7.90 (dd, J = 6.9, 2.3, 1H), 7.79 (d, J = 9.4, 1H), 7/8-7.73 (m, 1H), 7.62 (d, J = 5.6, 1H), 7.48 (dd, J = 9.5, 2.6, 1H), 7.41 (dd, J = 9.9, 8.5, 1H), 7.18 (d, J = 2.6, 1H), 7.16 (d, J = 4.7, 1H), 6.36 (d, J = 4.5, 1H), 3.82- 3.74 (m, 4H), 3.48-3.40 (m, 4H). 407 2-[2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-2-(5-methyl- pyrimidin-4-yl)- acetamide A B B MS: 475.2/477.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (400 MHz, DMSO-d6) ppm = 9.06 (s, intensity ratio [%] 100:36) 1H), 8.95 (s, 1H), 8.64-8.60 (m, 1H), 7.89 (d, J = 9.5, 1H), 7.85-7.79 (m, 1H), 7.76-7.67 (m, 3H), 7.54 (dd, J = 9.4, 2.6, 1H), 7.42-7.34 (m, 1H), 7.20 (d, J = 2.5, 1H), 5.67 (s, 1H), 3.84-3.74 (m, 4H), 3.50-3.42 (m, 4H), 2.31 (s, 3H). 408 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(5-methoxy- pyrimidin-4-yl)- methanol (Ena 2) B B C MS: 464.2/466.2 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:36); R.sub.t 5.41 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 409 0 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(5-methoxy- pyrimidin-4-yl)- methanol (Ena 1) B B A MS: 464.1/466.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:35); R.sub.t 3.05 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 410 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol (Ena 2) A A D MS: 464.2/466.2 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:35); R.sub.t 5.47 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 411 (S)-[2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol (Ena 1) B B C MS: 464.1/466.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:35); R.sub.t 2.84 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 412 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(5-fluoro- pyrimidin-4-yl)- methanol C C B MS: 452.1/454.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, intensity ratio [%] 100:35) 1H), 9.03 (d, J = 2.9, 1H), 8.93 (d, J = 2.1, 1H), 8.24 (d, J = 2.2, 1H), 7.96 (d, J = 9.4, 1H), 7.74 (dd, J = 8.2, 2.3, 1H), 7.62 (d, J = 8.2, 1H), 7.59 (dd, J = 9.5, 2.6, 1H), 7.23 (d, J = 2.5, 1H), 6.77 (d, J = 5.5, 1H), 6.38 (d, J = 5.5, 1H), 3.82-3.76 (m, 4H), 3.49-3.44 (m, 4H). 413 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(5-methoxy- pyrimidin-4-yl)- methanol B B B MS: 464.2/466.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, intensity ratio [%] 100:36) 1H), 8.74 (s, 1H), 8.64 (s, 1H), 8.15 (d, J = 2.2, 1H), 7.95 (d, J = 9.4, 1H), 7.69 (dd, J = 8.2, 2.3, 1H), 7.57 (dd, J = 8.9, 2.8, 2H), 7.22 (d, J = 2.5, 1H), 6.43 (d, J = 6.0, 1H), 6.31 (d, J = 6.0, 1H), 4.01 (s, 3H), 3.83-3.74 (m, 4H), 3.50-3.41 (m, 4H). 414 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[3,2-d}- pyrimidin-4-yl- methanol (Ena 2) C A C MS: 474.1/476.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:34); R.sub.t 6.16 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 415 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[3,2-d}- pyrimidin-4-yl- methanol (Ena 1) B A C MS: 474.1/476.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:35); R.sub.t 3.19 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 416 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[2,3-d}- pyrimidin-4-yl- methanol B B C MS: 474.1/476.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.07 (s, intensity ratio [%] 100:34) 1H), 8.88 (s, 1H), 8.20 (d, J = 2.5, 1H), 8.03 (d, J = 2.2, 1H), 7.84 (d, J = 9.4, 1H), 7.72 (dd, J = 8.2, 2.2, 1H), 7.65 (d, J = 8.3, 1H), 7.52 (dd, J = 9.4, 2.6, 1H), 7.26 (d, J = 2.5, 1H), 7.20 (d, J = 2.5, 1H), 6.88- 6.72 (m, 1H), 6.46 (s, 1H), 3.82-3.76 (m, 4H), 3.48-3.42 (m, 4H). 417 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(5-methyl- pyrimidin-4-yl)- methanol (Ena 2) C B B MS: 448.1/450.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:36); R.sub.t 6.39 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 418 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(5-methyl- pyrimidin-4-yl)- methanol (Ena 1) C B A MS: 448.1/450.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:36); R.sub.t 4.95 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 419 0 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(5-methyl- pyrimidin-4-yl)- methanol C B B MS: 448.1/450.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (400 MHz, DMSO-d6) ppm = 9.10 (s, intensity ratio [%] 100:37 1H), 8.94 (s, 1H), 8.67 (s, 1H), 8.16 (d, J = 2.2, 1H), 7.98 (d, J = 9.4, 1H), 7.72 (dd, J = 8.2, 2.2, 1H), 7.64-7.53 (m, 2H), 7.22 (d, J = 2.5, 1H), 6.47 (d, J = 6.0, 1H), 6.25 (d, J = 6.0, 1H), 3.84-3.73 (m, 4H), 3.51-3.42 (m, 4H), 2.49 (s, 3H). 420 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(9-methyl- 9H-purin-6-yl)- methanol C C A MS: 472.3 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, 1H), 8.91 (s, 1H), 8.55 (s, 1H), 7.82-7.73 (m, 2H), 7.56-7.47 (m, 2H), 7.40-7.31 (m, 1H), 7.19 (d, J = 1.3, 1H), 6.43 (d, J = 3.0, 1H), 6.30 (d, J = 5.2, 1H), 3.83 (s, 3H), 3.81-3.75 (m, 4H), 3.47- 3.40 (m, 4H). 421 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(9-methyl- 9H-purin-6-yl)- methanol C B A MS: 490.3 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 8.90 (s, 1H), 8.56 (s, 1H), 8.07 (t, J = 8.2, 1H), 7.66 (dd, J = 9.4, 2.9, 1H), 7.56 (dd, J = 9.4, 2.5, 1H), 7.38 (t, J = 10.1, 1H), 7.21 (d, J = 2.4, 1H), 6.61 (d, J = 4.8, 1H), 6.48 (d, J = 5.6, 1H), 3.85 (s, 3H), 3.82-3.75 (m, 4H), 3.52-3.43 (m, 4H). 422 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol B B C MS: 464.1/466.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, intensity ratio [%] 100:37) 1H), 8.19-8.14 (m, 2H), 8.11 (d, J = 2.7, 1H), 7.95 (d, J = 9.4, 1H), 7.69 (dd, J = 8.2, 2.3, 1H), 7.60- 7.53 (m, 2H), 7.22 (d, J = 2.6, 1H), 6.38 (d, J = 5.8, 1H), 6.27 (d, J = 5.8, 1H), 4.00 (s, 3H), 3.82-3.75 (m, 4H), 3.49-3.42 (m, 4H). 423 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(7-methyl- 7H-purin-6-yl)- methanol C C A MS: 506.2/4508.3 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.14 (s, intensity ratio [%] 100:40) 1H), 8.83 (s, 1H), 8.69 (s, 1H), 8.01 (d, J = 7.8, 1H), 7.71-7.63 (m, 2H), 7.59 (dd, J = 9.4, 2.5, 1H), 7.22 (d, J = 2.4, 1H), 6.87 (d, J = 6.3, 1H), 6.66 (d, J = 6.3, 1H), 4.25 (s, 3H), 3.84-3.73 (m, 4H), 3.52- 3.42 (m, 4H). 424 1-(3-{[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}pyrazin-2-yl)- 3-methyl- imidazolidin-2-one D D A MS: 516.4 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.50 (d, J = 2.4, 1H), 8.43 (d, J = 2.4, 1H), 7.69- 7.59 (m, 2H), 7.59-7.49 (m, 2H), 7.35 (t, J = 9.2, 1H), 7.19 (d, J = 1.9, 1H), 6.23 (d, J = 4.4, 1H), 5.95 (d, J = 5.3, 1H), 3.85 (t, J = 7.8, 2H), 3.82-3.73 (m, 4H), 3.52-3.40 (m, 6H), 2.78 (s, 3H). 425 1-(3-{[4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}pyrazin-2-yl)- pyrrolidin-2-one D D A MS: 501.4 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.61 (d, J = 2.4, 1H), 8.52 (d, J = 2.4, 1H), 7.65- 7.56 (m, 2H), 7.56-7.49 (m, 2H), 7.36 (t, J = 9.5, 1H), 7.19 (s, 1H), 6.02 (s, 2H), 3.89-3.82 (m, 1H), 3.81-3.74 (m, 4H), 3.74-3.64 (m, 1H), 3.50-3.39 (m, 4H), 2.57-2.41 (m, 2H), 2.17- 2.08 (m, 1H), 2.07-1.98 (m, 1H). 426 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)- methanol (Ena 2) C B A MS: 448.1/450.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:36); R.sub.t 5.95 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 427 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)- methanol (Ena 1) C B B MS: 448.1/450.2 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:31); R.sub.t 3.91 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 428 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)- methanol C A C MS: 448.2/450.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, intensity ratio [%] 100:36) 1H), 8.43 (d, J = 2.5, 1H), 8.36 (d, J = 2.5, 1H), 8.18 (d, J = 2.2, 1H), 7.97 (d, J = 9.4, 1H), 7.71 (dd, J = 8.2, 2.3, 1H), 7.61-7.54 (m, 2H), 7.22 (d, J = 2.6, 1H), 6.41 (d, J = 5.8, 1H), 6.30 (d, J = 5.8, 1H), 3.81-3.75 (m, 4H), 3.49-3.42 (m, 4H), 2.76 (s, 3H). 429 0 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]thieno[2,3-d}- pyrimidin-4-yl- methanol A A D MS: 508.1/510.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.07 (s, intensity ratio [%] 100:40) 1H), 9.05 (s, 1H), 8.46 (d, J = 5.6, 1H), 7.75 (d, J = 7.6, 1H), 7.72 (d, J = 9.6, 1H), 7.61 (d, J = 5.6, 1H), 7.55-7.49 (m, 2H), 7.20 (d, J = 5.0, 1H), 7.19- 7.17 (m, 1H), 6.42 (d, J = 5.1, 1H), 3.80-3.75 (m, 4H), 3.46-3.42 (m, 4H). 430 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thieno[2,3-d}- pyrimidin-4-yl- methanol B A A MS: 490.2/492.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.06 (s, intensity ratio [%] 100:40) 1H), 9.04 (s, 1H), 8.47 (d, J = 5.6, 1H), 7.89 (d, J = 2.1, 1H), 7.76 (d, J = 9.4, 1H), 7.73 (dd, J = 8.2, 2.2, 1H), 7.69 (d, J = 8.3, 1H), 7.62 (d, J = 5.5, 1H), 7.47 (dd, J = 9.5, 2.6, 1H), 7.20-7.16 (m, 2H), 6.47 (d, J = 4.9, 1H), 3.80-3.75 (m, 4H), 3.46- 3.41 (m, 4H). 431 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(7-methyl- 7H-purin-6-yl)- methanol C B A MS: 490.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, 1H), 8.85 (s, 1H), 8.67 (s, 1H), 7.91 (t, J = 8.1, 1H), 7.64 (dd, J = 9.4, 3.2, 1H), 7.58 (dd, J = 9.4, 2.5, 1H), 7.46 (t, J = 10.1, 1H), 7.21 (d, J = 2.5, 1H), 6.82 (d, J = 6.5, 1H), 6.65 (d, J = 6.5, 1H), 4.19 (s, 3H), 3.81-3.76 (m, 4H), 3.49-3.44 (m, 4H). 432 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[3,2-d}- pyrimidin-4-yl- methanol C B C MS: 474.1/476.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, intensity ratio [%] 100:34) 1H), 9.02 (s, 1H), 8.59 (d, J = 2.3, 1H), 8.30 (d, J = 2.2, 1H), 7.96 (d, J = 9.4, 1H), 7.74 (dd, J = 8.2, 2.3, 1H), 7.62 (d, J = 8.2, 1H), 7.59 (dd, J = 9.5, 2.6, 1H), 7.28 (d, J = 2.3, 1H), 7.23 (d, J = 2.6, 1H), 6.79 (d, J = 5.2, 1H), 6.54 (d, J = 5.2, 1H), 3.83-3.75 (m, 4H), 3.50-3.42 (m, 4H). 433 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(7-methyl- 7H-purin-6-yl)- methanol C B A MS: 472.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, 1H), 8.90 (s, 1H), 8.60 (s, 1H), 7.68-7.60 (m, 2H), 7.56 (dd, J = 9.4, 2.8, 1H), 7.52 (dd, J = 9.4, 2.4, 1H), 7.44-7.38(m, 1H), 7.19 (d, J = 2.3, 1H), 6.84 (d, J = 5.5, 1H), 6.37 (d, J = 5.4, 1H), 4.04 (s, 3H), 3.81-3.75 (m, 4H), 3.47-3.41 (m, 4H). 434 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[2,3-d}- pyrimidin-4-yl- methanol A A A MS: 458.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 8.89 (s, 1H), 8.18 (d, J = 2.5, 1H), 7.77-7.72 (m, 2H), 7.54-7.47 (m, 2H), 7.40 (t, J = 9.5, 1H), 7.36 (d, J = 2.5, 1H), 7.20 (d, J = 2.2, 1H), 6.71 (d, J = 4.2, 1H), 6.13 (d, J = 4.2, 1H), 3.81-3.76 (m, 4H), 3.47-3.42 (m, 4H). 435 6-{[2-Chloro-4-fluoro- 5-(7-morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1-methyl-1H- pyridin-2-one B A A MS: 481.2/483.2 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, intensity ratio [%] 100:38) 1H), 7.77 (d, J = 9.5, 1H), 7.74 (d, J = 7.6, 1H), 7.60 (dd, J = 9.4, 3.3, 1H), 7.53 (dd, J = 9.4, 2.5, 1H), 7.33 (dd, J = 9.1, 7.0, 1H), 7.21 (d, J = 2.5, 1H), 6.62 (d, J = 6.3, 1H), 6.37 (dd, J = 9.1, 1.3, 1H), 6.06 (d, J = 6.2, 1H), 5.89-5.85 (m, 1H), 3.81-3.75 (m, 4H), 3.55 (s, 3H), 3.49-3.43 (m, 4H). 436 6-{[2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]hydroxy- methyl}-1-methyl-1H- pyridin-2-one B B A MS: 465.3 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 7.63 (t, J = 8.1, 1H), 7.59-7.51 (m, 3H), 7.38 (dd, J = 9.1, 7.0, 1H), 7.20 (d, J = 2.3, 1H), 6.60 (d, J = 5.9, 1H), 6.39-6.35 (m, 1H), 6.20-6.16 (m, 1H), 6.09 (d, J = 5.9, 1H), 3.81-3.75 (m, 4H), 3.49- 3.40 (m, 7H). 437 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thieno[2,3-d}- pyrimidin-4-yl- methanol A A C MS: 474.1 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 9.08 (s, 1H), 8.47 (d, J = 5.6, 1H), 7.78-7.73 (m, 2H), 7.61 (d, J = 5.6, 1H), 7.54-7.46 (m, 2H), 7.43-7.36 (m, 1H), 7.21-7.18 (m, 1H), 7.13 (d, J = 3.9, 1H), 6.12 (d, J = 3.9, 1H), 3.82-3.73 (m, 4H), 3.48-3.40 (m, 4H). 438 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thieno[3,2-d}- pyrimidin-4-yl- methanol A A C MS: 474.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 9.07 (s, 1H), 8.46 (s, 1H), 8.45 (s, 1H), 7.78- 7.73 (m, 2H), 7.60 (d, J = 5.5, 1H), 7.52-7.46 (m, 2H), 7.41-7.36 (m, 1H), 7.20-7.18 (m, 1H), 7.11 (d, J = 3.9, 1H), 6.12 (d, J = 3.9, 1H), 3.80- 3.75 (m, 4H), 3.46-3.41 (m, 4H). 439 0 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]thieno[3,2-d}- pyrimidin-4-yl- methanol A A C MS: 492.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.07 (s, 1H), 9.05 (s, 1H), 8.47 (d, J = 5.6, 1H), 7.76 (t, J = 8.0, 1H), 7.61 (d, J = 5.6, 1H), 7.54-7.46 (m, 3H), 7.21-7.16 (m, 2H), 6.32 (d, J = 4.8, 1H), 3.80- 3.74 (m, 4H), 3.46-3.41 (m, 4H). 440 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[3,2-d}- pyrimidin-4-yl- methanol (Ena 2) A A B MS: 492.1/494.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:38); R.sub.t 8.33 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 441 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[3,2-d}- pyrimidin-4-yl- methanol (Ena 1) A A C MS: 492.1/494.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:38); R.sub.t 3.83 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 442 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[3,2-d}- pyrimidin-4-yl- methanol (Ena 2) A A A MS: 458.2 (M + H+); R.sub.t 7.52 min (SFC, see racemate Chiralpak AD-H, CO.sub.2/40% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 443 [4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[3,2-d}- pyrimidin-4-yl- methanol (Ena 1) B B A* MS: 458.1 (M + H.sup.+); R.sub.t 3.43 min (SFC, Chiralpak see racemate AD-H, CO.sub.2/40% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 444 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[3,2-d}- pyrimidin-4-yl- methanol (Ena 2) A B A MS: 476.2 (M + H.sup.+); R.sub.t 9.29 min (SFC, Chiralpak see racemate AD-H, CO.sub.2/30% by vol. of methanol, 0.5% by vol. of diethylamine) 445 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[3,2-d}- pyrimidin-4-yl- methanol (Ena 1) B A A MS: 476.1 (M + H.sup.+); R.sub.t 5.74 min (SFC, Chiralpak see racemate AD-H, CO.sub.2/30% by vol. of methanol, 0.5% by vol. of diethylamine) 446 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[3,2-d}- pyrimidin-4-yl- methanol A B A MS: 476.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, 1H), 9.00 (s, 1H), 8.57 (d, J = 2.3, 1H), 8.00 (t, J = 8.1, 1H), 7.59 (dd, J = 9.4, 2.8, 1H), 7.56 (dd, J = 9.4, 2.4, 1H), 7.45 (t, J = 10.1, 1H), 7.27 (d, J = 2.3, 1H), 7.21 (d, J = 2.3, 1H), 6.75 (d, J = 5.4, 1H), 6.43 (d, J = 5.3, 1H), 3.81-3.76 (m, 4H), 3.49- 3.42 (m, 4H). 447 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(5-methoxy- pyrimidin-4-yl)- methanol A B C MS: 482.2/484.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (400 MHz, DMSO-d6) ppm = 9.14 (s, intensity ratio [%] 100:40) 1H), 8.74 (s, 1H), 8.65 (s, 1H), 7.97 (d, J = 7.9, 1H), 7.69-7.52 (m, 3H), 7.23 (d, J = 2.4, 1H), 6.43- 6.32 (m, 2H), 4.01 (s, 3H), 3.80 (dd, J = 5.9, 3.9, 4H), 3.47 (t, J = 4.9, 4H). 448 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(5-methoxy- pyrimidin-4-yl)- methanol A B C MS: 466.2 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 8.77 (s, 1H), 8.62 (s, 1H), 7.86 (t, J = 8.2, 1H), 7.66-7.50 (m, 2H), 7.41 (t, J = 10.1, 1H), 7.21 (d, J = 2.1, 1H), 6.32 (d, J = 6.2, 1H), 6.25 (d, J = 6.3, 1H), 3.97 (s, 3H), 3.78 (t, J = 4.9, 4H), 3.45 (t, J = 4.9, 4H). 449 00 (3-Difluoromethoxy- pyrazin-2-yl)-[2,4- difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol (Ena 2) A B A MS: 502.2 (M + H.sup.+); R.sub.t 3.40 min (SFC, Chiralpak see racemate AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 450 01 (3-Difluoromethoxy- pyrazin-2-yl)-[2,4- difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol (Ena 1) C C B MS: 502.2 (M + H.sup.+); R.sub.t 2.00 min (SFC, Chiralpak see racemate AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 451 02 (3-Difluoromethoxy- pyrazin-2-yl)-[2,4- difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol B B B MS: 502.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.12 (s, 1H), 8.49 (d, J = 2.6, 1H), 8.32 (d, J = 2.6, 1H), 7.91 (t, J = 8.2, 1H), 7.77 (t, J = 71.7, 1H), 7.61-7.51 (m, 2H), 7.43 (t, J = 10.1, 1H), 7.21 (d, J = 2.4, 1H), 6.48 (d, J = 5.9, 1H), 6.29 (d, J = 4.7, 1H), 3.81- 3.75 (m, 4H), 3.48-3.42 (m, 4H). 452 03 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[3,2-d}- pyrimidin-4-yl- methanol A A C MS: 492.1/494.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.15 (s, intensity ratio [%] 100:41) 1H), 9.01 (s, 1H), 8.59 (d, J = 2.3, 1H), 8.11 (d, J = 7.7, 1H), 7.67 (d, J = 9.4, 1H), 7.64 (dd, J = 9.4, 2.9, 1H), 7.59 (dd, J = 9.4, 2.5, 1H), 7.29 (d, J = 2.3, 1H), 7.24 (d, J = 2.4, 1H), 6.85 (d, J = 5.4, 1H), 6.50 (d, J = 5.3, 1H), 3.83-3.77 (m, 4H), 3.51-3.44 (m, 4H). 453 04 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol (Ena 1) B A C MS: 466.1 (M + H.sup.+); R.sub.t 2.76 min (SFC, Chiralpak see racemate AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 454 05 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol (Ena 2) A A A MS: 466.2 (M + H.sup.+); R.sub.t 4.60 min (SFC, Chiralpak see racemate AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 455 06 (R)-[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol A A B MS: 482.1/484.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:36); R.sub.t 5.48 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 456 07 (S)-[2-Chloro-4- fluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol A A C MS: 482.1/484.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:35); R.sub.t 2.58 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of methanol, 0.5% by vol. of diethylamine) 457 08 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methyl- pyrazin-2-yl)- methanol B A A MS: 466.1/468.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.13 (s, intensity ratio [%] 100:36) 1H), 8.43 (d, J = 2.5, 1H), 8.36 (d, J = 2.5, 1H), 7.99 (d, J = 7.8, 1H), 7.67-7.60 (m, 2H), 7.57 (dd, J = 9.4, 2.5, 1H), 7.22 (d, J = 2.4, 1H), 6.44 (d, J = 5.9, 1H), 6.25 (d, J = 5.6, 1H), 3.86-3.72 (m, 4H), 3.52-3.42 (m, 4H), 2.74 (s, 3H). 458 09 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6-methoxy- pyridazin-3-yl)- methanol (Ena 1) A A C MS: 464.1/466.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (400 MHz, DMSO-d6) ppm = 9.08 (s, intensity ratio [%] 100:36); R.sub.t 11.22 min (SFC, 1H), 8.07 (d, J = 2.2, 1H), 7.89 (d, J = 9.5, 1H), 7.73- Chiralcel OJ-H, CO.sub.2/15% by vol. of 2-propanol, 7.67 (m, 2H), 7.63 (d, J = 8.2, 1H), 7.54 (dd, 0.5% by vol. of diethylamine) J = 9.5, 2.6, 1H), 7.24-7.19 (m, 2H), 6.59 (d, J = 4.8, 1H), 6.28 (d, J = 4.8, 1H), 4.00 (s, 3H), 3.82- 3.75 (m, 4H), 3.48-3.41 (m, 4H). 459 0 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6-methoxy- pyridazin-3-yl)- methanol (Ena 2) B B A* MS: 464.1/466.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:36); R.sub.t 14.88 min (SFC, Chiralcel OJ-H, CO.sub.2/15% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 460 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(6-methoxy- pyridazin-3-yl)- methanol B A A* MS: 464.1/466.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, intensity ratio [%] 100:36) 1H), 8.08 (d, J = 2.2, 1H), 7.89 (d, J = 9.5, 1H), 7.73- 7.67 (m, 2H), 7.63 (d, J = 8.2, 1H), 7.54 (dd, J = 9.4, 2.7, 1H), 7.23-7.19 (m, 2H), 6.59 (d, J = 4.9, 1H), 6.28 (d, J = 4.8, 1H), 4.00 (s, 3H), 3.81- 3.75 (m, 4H), 3.48-3.42 (m, 4H). 461 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methyl- 3H-imidazo[4,5-c]- pyridin-4-yl)methanol A A A* MS: 471.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.08 (s, 1H), 8.33 (s, 1H), 8.25 (d, J = 5.5, 1H), 7.62 (d, J = 5.5, 1H), 7.61-7.50 (m, 4H), 7.42-7.37 (m, 1H), 7.19 (d, J = 2.3, 1H), 6.61 (d, J = 5.5, 1H), 6.43 (d, J = 5.4, 1H), 4.01 (s, 3H), 3.80-3.74 (m, 4H), 3.46-3.41 (m, 4H). 462 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-iodo- pyrazin-2-yl)- methanol A A B MS: 544.1 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.62 (d, J = 2.4, 1H), 8.37 (d, J = 2.4, 1H), 7.69- 7.61 (m, 2H), 7.58-7.49 (m, 2H), 7.44-7.36 (m, 1H), 7.22-7.17 (m, 1H), 6.33 (d, J = 5.7, 1H), 6.17 (d, J = 5.7, 1H), 3.81-3.75 (m, 4H), 3.47-3.41 (m, 4H). 463 (3-Ethoxy-pyridin-2- yl)-[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol B A B MS: 461.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.14 (dd, J = 4.7, 1.2, 1H), 7.63-7.55 (m, 2H), 7.55-7.47 (m, 2H), 7.41 (dd, J = 8.3, 1.3, 1H), 7.38-7.31 (m, 1H), 7.29 (dd, J = 8.3, 4.7, 1H), 7.21-7.17 (m, 1H), 6.07 (d, J = 6.3, 1H), 5.79 (d, J = 6.6, 1H), 4.06 (q, J = 7.0, 2H), 3.81-3.75 (m, 4H), 3.47-3.41 (m, 4H), 1.28 (t, J = 6.9, 3H). 464 (3-Difluoromethoxy- pyrazin-2-yl)-[4- fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol B B B MS: 484.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 8.51 (d, J = 2.6, 1H), 8.28 (d, J = 2.6, 1H), 7.86- 7.55 (m, 3H), 7.54-7.49 (m, 2H), 7.43-7.36 (m, 1H), 7.22-7.17 (m, 1H), 6.30 (d, J = 5.6, 1H), 6.10 (d, J = 4.9, 1H), 3.83-3.73 (m, 4H), 3.48-3.40 (m, 4H). 465 (3-Chloro-pyridin-2- yl)-[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol (Ena 2) A A B MS: 451.1/453.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:35); R.sub.t 6.63 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 466 (3-Chloro-pyridin-2- yl)-[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol (Ena 1) C B B MS: 451.1/453.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:35); R.sub.t 3.98 min (SFC, Chiralpak AD-H, CO.sub.2/40% by vol. of 2-propanol, 0.5% by vol. of diethylamine) 467 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol B A A MS: 466.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 8.16 (dd, J = 16.4, 2.7, 2H), 7.87 (1, J = 8.2, 1H), 7.59 (dd, J = 9.4, 3.0, 1H), 7.56 (dd, J = 9.4, 2.4, 1H), 7.40 (t, J = 10.1, 1H), 7.21 (d, J = 2.5, 1H), 6.28 (s, 1H), 6.23 (s, 1H), 3.96 (s, 3H), 3.81- 3.75 (m, 4H), 3.49-3.43 (m, 4H). 468 [2-Chloro-4-fluoro-5- (7-morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methoxy- pyrazin-2-yl)- methanol A A B MS: 482.1/484.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.13 (s, intensity ratio [%] 100:37) 1H), 8.17 (d, J = 2.7, 1H), 8.11 (d, J = 2.7, 1H), 7.97 (d, J = 7.8, 1H), 7.65-7.58 (m, 2H), 7.56 (dd, J = 9.4, 2.5, 1H), 7.22 (d, J = 2.4, 1H), 6.31 (s, 2H), 4.00 (s, 3H), 3.81-3.76 (m, 4H), 3.48-3.43 (m, 4H). 469 0 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]pyridazin-3-yl- methanol (Ena 2) D D C MS: 434.1/436.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:38); R.sub.t 4.70 min (SFC, Chiralcel OJ-H, CO.sub.2/20% by vol. of methanol, 0.5% by vol. of diethylamine) 470 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]pyridazin-3-yl- methanol (Ena 1) B A A MS: 434.1/436.1 (M + H.sup.+) (Cl isotopy, rel. peak see racemate intensity ratio [%] 100:38); R.sub.t 2.52 min (SFC, Chiralcel OJ-H, CO.sub.2/20% by vol. of methanol, 0.5% by vol. of diethylamine) 471 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]furo[3,2-d}- pyrimidin-4-yl- methanol A A A* MS: 458.1 (M + H+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 9.01 (s, 1H), 8.55 (d, J = 2.3, 1H), 7.79-7.73 (m, 2H), 7.54-7.49 (m, 2H), 7.44-7.38 (m, 1H), 7.24 (d, J = 2.2, 1H), 7.22-7.18 (m, 1H), 6.62 (d, J = 4.6, 1H), 6.20 (d, J = 4.6, 1H), 3.80-3.75 (m, 4H), 3.47-3.42 (m, 4H). 472 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-methyl- pyridin-2-yl)methanol B A A MS: 431.2 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.08 (s, 1H), 8.43-8.39 (m, 1H), 7.63-7.57 (m, 1H), 7.56-7.49 (m, 4H), 7.39-7.32 (m, 1H), 7.28- 7.23 (m, 1H), 7.21-7.17 (m, 1H), 6.09 (s, 1H), 6.01 (s, 1H), 3.82-3.73 (m, 4H), 3.48-3.40 (m, 4H), 2.28 (s, 3H). 473 (3-bromo-5-methoxy- pyridin-2-yl)-[4- fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol B A B MS: 525.1/527.1 (M + H.sup.+) (Br isotopy, rel. peak 1H NMR (400 MHz, DMSO-d6) ppm = 9.09 (s, intensity ratio [%] 100:97) 1H), 8.31 (d, J = 2.6, 1H), 7.70 (d, J = 2.6, 1H), 7.62- 7.56 (m, 2H), 7.54-7.50 (m, 2H), 7.39-7.33 (m, 1H), 7.21-7.18 (m, 1H), 6.16 (d, J = 6.1, 1H), 6.01 (d, J = 6.1, 1H), 3.84 (s, 3H), 3.80-3.75 (m, 4H), 3.46-3.41 (m, 4H). 474 [2,4-Difluoro-5-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]imidazo- [2,1-b]thiazol-6-yl- methanol D D C MS: 480.1 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.09 (s, 1H), 7.85 (d, J = 4.5, 1H), 7.71-7.68 (m, 1H), 7.62- 7.55 (m, 1H), 7.54-7.51 (m, 2H), 7.26 (t, J = 9.1, 1H), 7.21-7.17 (m, 2H), 6.18-6.13 (m, 2H), 3.80-3.75 (m, 4H), 3.47-3.41 (m, 4H). 475 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-trifluoro- methoxypyridin-2-yl)- methanol A A B MS: 501.2 (M + H.sup.+) 1H NMR (400 MHz, DMSO-d6) ppm = 9.11 (s, 1H), 8.61 (dd, J = 4.6, 1.3, 1H), 7.87 (dp, J = 8.4, 1.6, 1H), 7.69-7.57 (m, 2H), 7.57-7.46 (m, 3H), 7.40 (dd, J = 9.9, 8.4, 1H), 7.21 (d, J = 1.9, 1H), 6.26 (d, J = 5.9, 1H), 6.13 (d, J = 5.9, 1H), 3.89-3.65 (m, 4H), 3.54-3.38 (m, 4H). 476 [4-Fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]-(3-trifluoro- methylpyrazin-2-yl)- methanol B A A MS: 486.2 (M + H.sup.+) 1H NMR (500 MHz, DMSO-d6) ppm = 9.10 (s, 1H), 9.00 (d, J = 2.3, 1H), 8.77 (d, J = 2.3, 1H), 7.66 (dd, J = 6.9, 2.3, 1H), 7.63-7.59 (m, 1H), 7.56- 7.50 (m, 2H), 7.43-7.37 (m, 1H), 7.21-7.18 (m, 1H), 6.54 (d, J = 5.7, 1H), 6.21 (d, J = 4.3, 1H), 3.81- 3.74 (m, 4H), 3.48-3.40 (m, 4H). 478 (3-bromo-pyridin-2- yl)-[4-fluoro-3-(7- morpholin-4-yl- quinazolin-4-yl)- phenyl]methanol A A D MS: 495.1/497.1 (M + H.sup.+) (Br isotopy, rel. peak 1H NMR (400 MHz, DMSO-d6) ppm = 9.09 (s, intensity ratio [%] 100:96) 1H), 8.60 (dd, J = 4.6, 1.4, 1H), 8.08 (dd, J = 8.1, 1.5, 1H), 7.65-7.59 (m, 2H), 7.54-7.50 (m, 2H), 7.41-7.34 (m, 1H), 7.29 (dd, J = 8.1, 4.6, 1H), 7.21-7.18 (m, 1H), 6.20 (d, J = 6.3, 1H), 6.12 (d, J = 6.3, 1H), 3.82-3.74 (m, 4H), 3.49-3.40 (m, 4H). 479 [2-Chloro-5-(7- morpholin-4-yl- quinazolin-4-yl)- pyenyl]pyridazin-3-yl- methanol B A B MS: 434.1/436.1 (M + H.sup.+) (Cl isotopy, rel. peak 1H NMR (500 MHz, DMSO-d6) ppm = 9.15 (dd, intensity ratio [%] 100:37) J = 4.9, 1.7, 1H), 9.08 (s, 1H), 8.04 (d, J = 2.2, 1H), 7.87 (d, J = 9.4, 1H), 7.80 (dd, J = 8.5, 1.7, 1H), 7.74- 7.69 (m, 2H), 7.64 (d, J = 8.2, 1H), 7.52 (dd, J = 9.5, 2.6, 1H), 7.21 (d, J = 2.5, 1H), 6.69 (d, J = 4.9, 1H), 6.38 (d, J = 4.9, 1H), 3.83-3.72 (m, 4H), 3.49-3.40 (m, 4H). *In the second column: enantiomer isolated by chromatography which represents either the pure R or S configuration of the molecule *In the final column: potassium channel activity measured using hERG binding assay instead of hERG patch clamp assay

(175) Example numbers 273-277, 281-283, 287 and 477 have intentionally been omitted.