PYRIDINIUM OXAZOLE DYAD SCAFFOLD AND A PROCESS FOR PREPARATION THEREOF

Abstract

The present invention relates to a pyridinium oxazole dyad scaffold of formula (I) and a process for the preparation thereof. The present invention further discloses a pyridine compound of formula (II) which is used for the preparation of formula (I) and a process for preparation thereof.

##STR00001##

Claims

1.-3. (canceled)

4. A pyridine compound of formula (II), ##STR00007## wherein; R.sub.1, R.sub.2 and R.sub.3 are same or different and each is independently selected from the group consisting of H, alkyl groups, alkenyl groups, aryl groups, heteroaryl groups, electron donating as well as electron withdrawing substituents; X is selected from the group consisting of H, alkyl, benzyl, aryl, OR, SR and NR; wherein R is selected from the group consisting of H, alkyl and aryl.

5.-8. (canceled)

9. A process for the preparation of pyridine compound of formula (II) as claimed in claim 4, wherein said process comprising the steps of: a) degassing the reaction mixture consisting of pyridine derivative, boronic acid in suitable solvent with nitrogen; b) adding sodium carbonate or potassium carbonate, Palladium catalyst to the reaction mixture of step a under continuous flow of nitrogen; c) heating the reaction mixture of step b at the temperature ranging from 70 to 80 C. for 4 to 10 hours to afford desired product of formula (II).

10. The process as claimed in claim 9, wherein said boronic acid of step (a) is 2 allkynyl phenyl boronic acid and said solvent of step (a) is DMF/H.sub.2O in a ratio of 1:1 and the said catalyst of step (b) is PdCl.sub.2(PPh.sub.3).sub.2.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

[0026] FIG. 1: Observed fluorescence under UV excitation (365 nm).

[0027] FIG. 2: In vitro imaging in MCF-7 cells. (a1 and b1): MCF-7 cells treated with 1 M 3h for 6 h; Scale bar=64 and 100 micron. (a2): MCF-7 cells treated with 1 M DAPI for 6 h; Scale bar=64 micron. (b2): MCF-7 cells treated with 1 M Mito Tracker Green (MG) for 1 h; Scale bar=100 micron. (a3): merging of red (a1) and blue (a2) fluorescence images of cells. (b3): merging of red (b1), green (b2) fluorescence images of cells and fluorescence images with DAPI

[0028] FIG. 3: Absorption of representative derivatives in DCM

[0029] FIG. 4: Emission of representative derivatives in DCM at RT

[0030] FIG. 5: Excitation of representative derivatives in DCM at RT

[0031] FIG. 6: MTT assay

DETAILED DESCRIPTION OF THE INVENTION

[0032] The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated.

[0033] The present invention provides a pyridinium oxazole dyad scaffold of formula (I).

##STR00004##

[0034] Wherein; R.sub.1, R.sub.2 and R.sub.3 are selected from the group consisting of H, alkyl groups, alkenyl groups, aryl groups, heteroaryl groups, such as electron donating as well as electron withdrawing substituents; R.sub.1, R.sub.2 and R.sub.3 may be similar or different;

[0035] X=CRR, O, S, NR wherein R and R are same or different and each is independently selected from the group consisting of H, alkyl, benzyl, or aryl; further R and R may form a cyclic ring having 4 to 6 carbon atoms.

[0036] In preferred embodiment, said compound of formula I is tunable in UV region and Tunable emission wavelength depends upon substituents.

[0037] In an embodiment, the present invention provides pyridinium-oxazole dyad salts of formula (I) with tunable emission wavelengths.

[0038] In another embodiment of the present invention, said pyridinium-oxazole dyad salts of formula (I) can be accessed utilizing gold (I)-catalyzed oxidative intramolecular 1,2-aminoxygenation reactions, combining gold(I)/gold(III) catalysis.

[0039] In still another embodiment, the present invention provides intramolecular 1,2-aminooxygenation of alkynes to access pyridinium-oxazole dyad salts with tunable emission wavelengths.

[0040] In yet another embodiment, the present invention provides di-functionalization of alkynes utilising gold (I)/gold (III) catalysis.

[0041] In still yet another embodiment, the present invention provides a process for the preparation of a Pyridinium oxazole dyad scaffold of formula (I) comprises heating the reaction mixture consisting of pyridine of formula (II), Selectfluor in suitable solvent in presence of gold catalyst at the temperature ranging from 70 to 80 C. for the time period ranging from 6 to 8 hours to afford Pyridinium oxazole dyad scaffold.

[0042] In preferred embodiment, said pyridinium oxazole dyad scaffold of formula (I) are selected from 1-phenylbenzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate, 1-(naphthalen-1-yl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-iumtetrafluoroborate, 1-(naphthalen-2-yl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-iumtetrafluoroborate, 1-(phenanthren-9-yl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate, 1-(p-tolyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate, 1-(4-isopropylphenyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate, 1-(4-pentylphenyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate, 1-(4-methoxyphenyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate, 1-(4-butoxyphenyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium, 1-(4-fluoro phenyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-iumtetrafluoroborate, 1-(4-chlorophenyl) benzo[a]oxazolo[4,3,2-cd]indolizin-10-iumtetrafluoroborate, 1-(4-(dimethylamino)phenyl) benzo[a]oxazolo[4,3,2-cd]indolizin-10-iumtetrafluoroborate, 1-(4-pentanoylphenyl) benzo[a]oxazolo[4,3,2-cd]indolizin-10-iumtetrafluoroborate, 1-(2-methoxyphenyl) benzo[a]oxazolo[4,3,2-cd]indolizin-10-iumtetrafluoroborate,1-(3-methoxyphenyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-iumtetrafluoroborate, 1-(3-chlorophenyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-iumtetrafluoroborate,6-methyl-1-phenylbenzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate, 7-methyl-1-phenylbenzo[a]oxazolo[4,3,2-cd]indolizin-10-iumtetrafluoroborate,7-fluoro-1-phenylbenzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoro borate, 7-chloro-1-phenylbenzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate, 1-phenyldibenzo[a,f]oxazolo[4,3,2-cd]indolizin-12-ium tetrafluoroborate.

[0043] The scheme 1 is as shown below

##STR00005##

[0044] In another preferred embodiment, said solvent system is selected from acetonitrile (CH.sub.3CN), dichloromethane (CH.sub.2Cl.sub.2), chloroform (CHCl.sub.3) and toluene.

[0045] In still another preferred embodiment, said gold catalyst is selected from Chloro(triphenylphosphine)gold(I) (PPh.sub.3AuCl), Triphenylphosphine Gold(I) Trifluoromethanesulfonate (PPh.sub.3AuOTf), Chloro[(1,1-biphenyl-2-yl)di-tert-butylphosphine]gold(I) (JohnPhosAuCl), Chloro-(2-Biphenyl)dicyclohexylphosphine gold(I) (CyJohnPhosAuCl), tBuCyJhonAuCl, Chloro-tris(4 fluro-triphenylphosphine)gold(I) (4-FC.sub.6H.sub.4).sub.3PAuCl, Chloro-tris(4 trifluromethyl-triphenylphosphine)gold(I) (4-CF.sub.3C.sub.6H.sub.4).sub.3PAuCl, Chloro-Tris(pentafluorophenyl)phosphine) gold (I) (C.sub.6F.sub.5).sub.3PAuCl.

[0046] In still yet another embodiment, the present invention provides pyridine of formula (II) which is used for the preparation of formula (I).

##STR00006##

[0047] Wherein; R.sub.1, R.sub.2 and R.sub.3 are selected from the group consisting of H, alkyl groups, alkenyl groups, aryl groups, heteroaryl groups, such as electron donating as well as electron withdrawing substituents; R.sub.1, R.sub.2 and R.sub.3 may be similar or different;

[0048] X=H, alkyl, benzyl, aryl, OR, SR, NR; wherein RH, alkyl or aryl.

[0049] In a preferred embodiment, said compound of formula (II) are selected from 2-(tert-butoxy)-6-(2-(phenylethynyl)phenyl)pyridine,2-(tert-butoxy)-6-(2-(naphthalen-1-ylethynyl)phenyl) pyridine,2-(tert-butoxy)-6-(2-(naphthalen-2-ylethynyl)phenyl)pyridine, 2-(tert-butoxy)-6-(2-(phenanthren-9-ylethynyl)phenyl)pyridine,2-(tert-butoxy)-6-(2-(hept-1-yn-1-yl)phenyl) pyridine,2-(tert-butoxy)-6-(2-(cyclohex-1-en-1-ylethynyl)phenyl)pyridine, 2-(tert-butoxy)-6-(2-(p-tolylethynyl)phenyl)pyridine, 2-(tert-butoxy)-6-(2-((4-isopropylphenyl)ethynyl) phenyl)pyridine,2-(tert-butoxy)-6-(2-((4-pentylphenyl)ethynyl)phenyl)pyridine,2-(tert-butoxy)-6-(2-((4-methoxyphenyl)ethynyl)phenyl)pyridine,2-(tert-butoxy)-6-(2-((4-butoxyphenyl)ethynyl)phenyl)pyridine,2-(tert-butoxy)-6-(2-((4-fluorophenyl) ethynyl)phenyl)pyridine,2-(tert-butoxy)-6-(2-((4-chlorophenyl)ethynyl)phenyl)pyridine, 4-((2-(6-(tert-butoxy)pyridin-2-yl)phenyl)ethynyl)-N,N-dimethylaniline, 1-(4-((2-(6-(tert-butoxy)pyridin-2-yl)phenyl)ethynyl)phenyl)pentan-1-one,2-(tert-butoxy)-6-(2-((2-methoxyphenyl)ethynyl)phenyl)pyridine,2-(tert-butoxy)-6-(2-((3-methoxyphenyl) ethynyl)phenyl)pyridine,2-(tert-butoxy)-6-(2-((3-chlorophenyl)ethynyl)phenyl)pyridine,2-(tert-butoxy)-6-(2-methyl-6-(phenylethynyl)phenyl)pyridine,2-(tert-butoxy)-6-(5-methyl-2-(phenylethynyl)phenyl)pyridine,2-(tert-butoxy)-6-(5-fluoro-2-(phenylethynyl)phenyl) pyridine, 2-(tert-butoxy)-6-(5-chloro-2-(phenylethynyl)phenyl)pyridine, 2-(tert-butoxy)-6-(4-chloro-2-(phenylethynyl)phenyl)pyridine, 1-methoxy-3-(2-(phenylethynyl)phenyl) isoquinoline,2-(tert-butoxy)-6-(2-((2-chloro-5-methoxyphenyl)ethynyl)phenyl)pyridine,2-(tert-butoxy)-6-(2-((3-chloro-4-methylphenyl)ethynyl)phenyl)pyridine,2-(tert-butoxy)-6-(3,5-dimethoxy-2-(phenylethynyl)phenyl)pyridine.

[0050] In still yet another embodiment, the present invention provides a process for the preparation of pyridine of formula (II) comprising the steps of [0051] a) degassing the reaction mixture consisting of pyridine derivative, boronic acid in suitable solvent with nitrogen; [0052] b) adding sodium carbonate or potassium carbonate, Palladium catalyst to the reaction mixture of step a under continuous flow of nitrogen; [0053] c) heating the reaction mixture of step b at the temperature ranging from 70 to 80 C. for 4 to 10 hours to afford desired product of formula (II).

[0054] In preferred embodiment, said boronic acid of step (a) is 2-alkylnyl aryl boronic acid preferably 2-allkynyl phenyl boronic acid.

[0055] In another preferred embodiment, said solvent is DMF/H.sub.2O in ratio 1:1.

[0056] In still another preferred embodiment, said Palladium catalyst of step (b) is PdCl.sub.2(PPh).sub.2.

[0057] In yet another embodiment, the present invention provides use of said compound of formula I for imaging application, particularly mitochondrial imaging for diagnosis of cancer.

[0058] In a preferred embodiment, said compound of formula I is used as a fluorescent agent for mitochondrial imaging.

[0059] In still yet another embodiment, the present invention provides cytotoxicity evaluation study of compound of formula I preferably 3n using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay (FIG. 6).

[0060] In still yet another embodiment, the present invention provides assessment of compound of formula I preferably 3n for its ability to localize and stain mitochondria in living cells by fluorescence microscope.

[0061] The novel compounds of the invention are brightly fluorescent. The compounds and the salts thereof are class of fluorescent materials containing a pyridinium-oxazole functional group.

[0062] The photo-physical properties of representative salts are studied in CH.sub.2Cl.sub.2 at RT (FIG. 1).

[0063] The corresponding absorption, emission and excitation, spectra are depicted in FIGS. 3, 4 and 5. The photoluminescence spectra of salts show intense peaks between em: 400-560 nm (FIG. 1) with Stokes shifts varies between (30-80 nm) which reveals violet-to-yellow fluorescence emissions depending on the functional group present in the salts. The compounds display good quantum yields upto 0.76.

[0064] The novel compounds of the invention may be useful as Organic light emitting diodes (OLED) materials for solution processing.

[0065] Table 1 shows Spectral properties of representative derivatives in DCM at Room temperature (RM) (10-5 M)

TABLE-US-00001 TABLE 1 Spectral properties of representative derivatives in DCM at RM (105M) .sub.abs .sub.em .sub.ex .sub.Stokes .sub.f Comp (nm).sup.a (nm).sup.b (nm).sup.c (nm).sup.d .sub.f.sup.e (nm).sup.f 3a 368 404 338 036 0.10 1.2 3m 370 410 339 040 0.19 1.7 3l 372 414 343 042 0.09 0.9 3q 376 455 332 079 0.20 2.0 3j 405 458 338 053 0.42 2.4 3c 410 481 364 071 0.49 5.2 3d 411 487 365 076 0.54 7.2 3n 506 555 511 049 0.76 9.1

[0066] a The maximum absorption bands more than 300 nm; b Excited at the longest maximum absorption band in CH.sub.2Cl.sub.2; .sup.cExcited wavelength; .sup.dStokes shift=em.sub.abs; .sup.eQuinine sulfate and rhodamine 6G was used as the standard; .sup.fFluorescent lifetime

[0067] The current invention provides compounds that display brightly fluorescence as well as a good .sub.f. The salts are a novel class of fluorescent materials that contain a pyridinium-oxazole functional group and the photo-physical properties of representative salts are studied in CH.sub.2Cl.sub.2 at RT The absorption and excitation maxima, the photoluminescence (PL) maxima and quantum yields (FF), as well as the excited state lifetimes (t.sub.f) of these compounds in CH.sub.2Cl.sub.2 solution are listed in Tables 3, whereas the corresponding absorption, emission, excitation spectra are depicted in FIGS. 3, 4 and 5. The photoluminescence spectra of salts show intense peaks between .sub.em: 400-560 nm (Table 3) with Stokes shifts varies between (30-80 nm) which reveals violet-to-yellow fluorescence emissions depending on the functional group present in the salts. Substituents like chloro and fluoro on the core had only a modest effect on the fluorescent properties (3l and 3j). When phenyl ring replaced by bulky substituents like 2-napthyl and 9-phenathryl on the core had stronger effect on the fluorescent properties (3c and 3d). The presence of stronger donar group like NMe.sub.2 leads to significant bathochromic shifts in emission (4a and 4h, and FIG. 1). These observations are indicative of a predominant -* character for the lowest excited state, and the life time t.sub.f values are consistent with a singlet multiplicity. Most of these compounds display good quantum yields upto 0.76 (3n). The radiative rate constants are barely affected by the substitution pattern, an indication of the similar excited state character for all compounds.

EXAMPLES

[0068] Following examples are given by way of illustration therefore should not be construed to limit the scope of the invention.

Example 1: General Procedure for Sonogashira Cross Coupling of Aryl Iodides with Different Substituted Acetylenes

[0069] A suspension of (un)substituted 2-bromoiodobenzene (2 gm, 7.06 mmol), PdCl.sub.2(PPh.sub.3).sub.2 (99.2 mg, 0.14 mmol, 2 mol %), Cu(I) iodide (40.2 mg, 0.21 mmol, 3 mol %) in 20 mL of triethylamine was degassed three times. After 10 min a solution of (un)substituted aryl/alkyl acetylene (0.84 mL, 7.77 mmol, 1.1 eq) in Et.sub.3N (3.6 mL) is added dropwise over 5 min via syringe and the reaction mixture is left to stir for 12 h and monitored by TLC. After total consumption of the 2-bromoiodobenzene, the reaction mixture was filtered through celite and extracted with EtOAc (310 mL). The organic layer was washed with a saturated solution of NH.sub.4Cl (210 mL), water (210 mL), dried over Na.sub.2SO.sub.4 and the solvent was removed under vacuo. The reaction mixture was purified by flash chromatography on silica gel, (eluent: pet. ether) to give the product (un)substituted bromo benzene as a yellow oil (S1, Yield 88%).

Example 2: General Procedure for Preparation of 2-Alkynylphenylboronic Acids

[0070] In a two-necked round bottom flask, 1.6 M solution of BuLi in hexanes (5.5 mL, 8.78 mmol, 1.5 eq) was added dropwise to a solution of 2-phenylethynyl bromobenzene (S.sub.1) (1.5 g, 5.85 mmol) in 45 mL of diethyl ether under nitrogen atmosphere at 78 C. The mixture was stirred at 78 C. for 1 h and then at 40 C. for 1 h then cooled back to 78 C. and B(O.sup.iPr).sub.3 (1.65 g, 8.78 mmol, 1.5 eq) is added dropwise. The mixture was allowed to warm up gradually to room temperature, while maintaining vigorous stirring for 16 h. Then, the reaction is quenched with 40 mL of 1N HCl for 30 minutes and extracted with EtOAc (320 mL). The combined organic solution is dried over Na.sub.2SO.sub.4 and the solvent was removed under vacuo. The product was purified by flash chromatography on silica gel, (eluent: pet. ether/EtOAc) followed by recrystallization from pet. ether to give the product (2-(phenylethynyl)phenyl)boronic acid (S.sub.27) as a white solid (Yield 84%).

Example 3: General Procedure for Preparation of Suzuki Coupling Reaction Between Bromo-Pyridines and Boronic Acids

[0071] In a sealed tube 2-bromo-6-.sup.tbutylypyridine (300 mg, 1.59 mmol) and (2-(phenylethynyl)phenyl)boronic acid (S.sub.20) (425 mg, 1.91 mmol, 1.2 eq) in DMF/H.sub.2O 1:1 (2 mL) was degassed with nitrogen for 5 min followed by addition of Na.sub.2CO.sub.3 (507 mg, 4.78 mmol, 3 eq) under continuous flow of nitrogen, PdCl.sub.2(PPh.sub.3).sub.2 (55.8 mg, 0.079 mmol, 5 mol %) were added to the reaction mixture under a nitrogen atmosphere. The reaction mixture was stirred at 80 C. for 12 h the solution was diluted with NaHCO.sub.3 (5 mL), and then the product is extracted with EtOAc (305 mL). The combined organic layer was dried over Na.sub.2SO.sub.4 and the solvent is removed under vacuo. The crude product was purified on a silica gel column using pet. ether/EtOAc as eluent to afford 2-methoxy-6-(2 (phenylethynyl)-phenyl) pyridine (1a) as a yellow thick liquid (Yield 84%).

a) 2-(tert-butoxy)-6-(2-(phenylethynyl)phenyl)pyridine (1a)

[0072] Thick liquid, 84% yield; R.sub.f=0.80 (Pet.Ether/EtOAc=95/05); .sup.1H NMR (500 MHz, CDCl.sub.3) =7.88 (d, J=7.6 Hz, 1H), 7.74-7.67 (m, 2H), 7.67-7.61 (m, 1H), 7.50-7.43 (m, 3H), 7.42-7.37 (m, 1H), 7.37-7.30 (m, 3H), 6.70 (d, J=8.0 Hz, 1H), 1.69 (s, 9H); .sup.13C NMR (125 MHz, CDCl.sub.3) =163.4, 154.2, 142.2, 137.8, 133.2, 131.4, 129.7, 128.4, 128.3, 128.2, 127.7, 123.5, 121.0, 116.6, 111.8, 92.6, 89.6, 79.4, 28.8; HRMS (ESI) calcd for C.sub.23H.sub.12ON (M.sup.++H) 328.1696, found 328.1694.

b) 2-(tert-butoxy)-6-(2-(naphthalen-1-ylethynyl)phenyl)pyridine (1b)

[0073] Yellowish solid, 78% yield; mp=108-109 C.; R.sub.f=0.85 (Pet.Ether/EtOAc=95/05); .sup.1H NMR (500 MHz, CDCl.sub.3) =8.28-8.21 (m, 1H), 7.98-7.94 (m, 1H), 7.92-7.85 (m, 3H), 7.81 (d, J=7.2 Hz, 1H), 7.78-7.74 (m, 1H), 7.69 (t, J=7.8 Hz, 1H), 7.59-7.53 (m, 3H), 7.52-7.46 (m, 2H), 6.82 (d, J=8.0 Hz, 1H), 1.75 (s, 9H); .sup.13C NMR (125 MHz, CDCl.sub.3) =163.6, 154.6, 142.5, 138.1, 133.3, 133.2, 133.1, 130.2, 129.7, 128.6, 128.5, 128.1, 127.8, 126.6, 126.3, 125.2, 121.3, 121.1, 116.8, 111.8, 94.3, 90.9, 79.5, 77.3, 76.7, 28.8; HRMS (ESI) calcd for C.sub.27H.sub.24ON (M.sup.++H) 378.1852, found 378.1850.

c) 2-(tert-butoxy)-6-(2-(phenanthren-9-ylethynyl)phenyl)pyridine (1d)

[0074] Yellowish solid, 68% yield; mp=86-87 C.; R.sub.f=0.85 (Pet.Ether/EtOAc=95/05); .sup.1H NMR (500 MHz, CDCl.sub.3) =8.66 (d, J=8.4 Hz, 1H), 8.69 (d, J=8.4 Hz, 1H), 8.24 (d, J=8.4 Hz, 1H), 7.99 (s, 1H), 7.90-7.80 (m, 3H), 7.73 (d, J=7.2 Hz, 1H), 7.71-7.55 (m, 6H), 7.53-7.48 (m, 1H), 7.47-7.41 (m, 1H), 6.74 (d, J=8.0 Hz, 1H), 1.66 (s, 9H); .sup.13C NMR (125 MHz, CDCl.sub.3) =163.6, 154.6, 142.6, 138.1, 133.4, 131.7, 131.2, 131.1, 130.2, 130.0, 129.8, 128.5, 127.8, 127.4, 127.1, 127.0, 126.9, 122.7, 122.6, 121.3, 119.9, 116.8, 111.9, 93.9, 91.1, 79.6, 28.9; HRMS (ESI) calcd for C.sub.31H.sub.26ON (M.sup.++H) 428.2009, found 428.2007.

d) 2-(tert-butoxy)-6-(2-(hept-1-yn-1-yl)phenyl)pyridine (1e)

[0075] Thick liquid, 56% yield; R.sub.f=0.70 (Pet.Ether/EtOAc=95/05); .sup.1H NMR (500 MHz, CDCl.sub.3) =7.82 (dd, J=1.1, 7.6 Hz, 1H), 7.66 (d, J=6.9 Hz, 1H), 7.60-7.53 (m, 2H), 7.40 (dt, J=1.1, 7.6 Hz, 1H), 7.34-7.28 (m, 1H), 6.66 (d, J=7.6 Hz, 1H), 2.40 (t, J=7.1 Hz, 2H), 1.69 (s, 9H), 1.43-1.34 (m, 4H), 0.94 (t, J=7.2 Hz, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) =163.3, 154.5, 141.9, 137.7, 133.4, 129.6, 127.6, 127.5, 121.8, 116.5, 111.5, 93.9, 80.5, 79.3, 31.1, 28.8, 28.1, 22.2, 19.6, 14.0; HRMS (ESI) calcd for C.sub.22H.sub.28ON (M.sup.++H) 322.2165, found 322.2165.

e) 2-(tert-butoxy)-6-(2-(p-tolylethynyl)phenyl)pyridine (1g)

[0076] Thick liquid, 82% yield; R.sub.f=0.80 (Pet.Ether/EtOAc=95/05); .sup.1H NMR (500 MHz, CDCl.sub.3) =7.90-7.82 (m, 1H), 7.70 (d, J=7.2 Hz, 1H), 7.68-7.64 (m, 1H), 7.64-7.59 (m, 1H), 7.47-7.42 (m, 1H), 7.39-7.31 (m, 3H), 7.15 (d, J=8.0 Hz, 2H), 6.67 (d, J=8.0 Hz, 1H), 2.37 (s, 3H), 1.66 (s, 9H); 13C NMR (125 MHz, CDCl.sub.3) =163.4, 154.3, 142.1, 138.3, 137.8, 133.2, 131.3, 129.7, 129.1, 128.2, 127.7, 121.2, 120.4, 116.6, 111.7, 92.8, 89.0, 79.4, 28.9, 21.5; HRMS (ESI) calcd for C.sub.24H.sub.24ON (M.sup.++H) 342.1852, found 342.1852.

f) 2-(tert-butoxy)-6-(2-((4-methoxyphenyl)ethynyl)phenyl)pyridine (1j)

[0077] Thick liquid, 76% yield; R.sub.f=0.70 (Pet.Ether/EtOAc=95/05); .sup.1H NMR (500 MHz, CDCl.sub.3) =7.91-7.82 (m, 1H), 7.72 (d, J=7.2 Hz, 1H), 7.69-7.60 (m, 2H), 7.48-7.42 (m, 1H), 7.42-7.34 (m, 3H), 6.88 (d, J=8.8 Hz, 2H), 6.69 (d, J=8.0 Hz, 1H), 3.82 (s, 3H), 1.68 (s, 9H); 13C NMR (125 MHz, CDCl.sub.3) =163.4, 159.6, 154.3, 142.0, 137.8, 133.0, 132.8, 129.7, 128.1, 127.7, 121.3, 116.6, 115.6, 113.9, 111.7, 92.6, 88.3, 79.4, 55.2, 28.8; HRMS (ESI) calcd for C.sub.24H.sub.24O.sub.2N (M.sup.++H) 358.1802, found 358.1801.

g) 2-(tert-butoxy)-6-(2-((4-fluorophenyl)ethynyl)phenyl)pyridine (1l)

[0078] Thick liquid, 65% yield; R.sub.f=0.70 (Pet.Ether/EtOAc=95/05); .sup.1H NMR (500 MHz, CDCl.sub.3) =7.87-7.81 (m, 1H), 7.68-7.60 (m, 3H), 7.49-7.44 (m, 1H), 7.44-7.34 (m, 3H), 7.07-6.98 (m, 2H), 6.68 (dd, J=1.9, 7.0 Hz, 1H), 1.66 (s, 9H); 13C NMR (125 MHz, CDCl.sub.3) =163.5, 163.4-161.4 (d, J=248.91 Hz), 154.3, 142.3, 137.8, 133.3-133.1 (d, J=14.31 Hz), 133.2, 129.8, 128.5, 127.7, 120.8, 119.6-119.6 (d, J=2.86 Hz), 116.5, 115.7-115.5 (d, J=21.94 Hz), 111.8, 91.4, 89.3, 79.5, 28.8; HRMS (ESI) calcd for C.sub.23H.sub.21ONF (M.sup.++H) 346.1602, found 346.1600.

h) 4-((2-(6-(tert-butoxy)pyridin-2-yl)phenyl)ethynyl)-N,N-dimethylaniline (1n)

[0079] Yellowish solid, 68% yield; mp=116-117 C.; R.sub.f=0.65 (Pet.Ether/EtOAc=95/05); .sup.1H NMR (500 MHz, CDCl.sub.3) =7.86 (d, J=7.6 Hz, 1H), 7.77 (d, J=6.9 Hz, 1H), 7.67-7.59 (m, 2H), 7.45-7.38 (m, 1H), 7.37-7.29 (m, 3H), 6.66 (d, J=9.2 Hz, 3H), 2.99 (s, 6H), 1.67 (s, 9H); .sup.13C NMR (125 MHz, CDCl.sub.3) =163.4, 154.4, 150.0, 141.5, 137.8, 132.8, 132.5, 129.6, 127.6, 127.6, 121.9, 116.7, 111.8, 111.5, 110.3, 94.0, 87.7, 79.3, 40.2, 28.9; HRMS (ESI) calcd for C.sub.25H.sub.27ON.sub.2 (M.sup.++H) 371.2118, found 371.2117.

i) 1-(4-((2-(6-(tert-butoxy)pyridin-2-yl)phenyl)ethynyl)phenyl)pentan-1-one (1o)

[0080] Thick liquid, 58% yield; R.sub.f=0.60 (Pet.Ether/EtOAc=95/05); .sup.1H NMR (500 MHz, CDCl.sub.3) =7.92 (d, J=8.3 Hz, 2H), 7.83 (d, J=7.3 Hz, 1H), 7.67 (d, J=7.8 Hz, 1H), 7.62 (q, J=7.7 Hz, 2H), 7.52-7.42 (m, 3H), 7.42-7.31 (m, 1H), 6.68 (d, J=7.3 Hz, 1H), 1.77-1.69 (m, 2H), 1.65 (s, 9H), 1.46-1.38 (m, 2H), 0.97 (t, J=7.3 Hz, 3H); 13C NMR (125 MHz, CDCl.sub.3) =199.7, 163.5, 154.1, 142.6, 137.9, 136.0, 133.3, 131.4, 129.8, 128.9, 128.1, 127.9, 127.8, 120.4, 116.5, 111.9, 92.9, 91.7, 79.5, 77.3, 76.7, 38.3, 28.8, 26.4, 22.4, 13.9; HRMS (ESI) calcd for C.sub.28H.sub.30O.sub.2N (M.sup.++H) 412.2271, found 412.2268.

j) 2-(tert-butoxy)-6-(5-methyl-2-(phenylethynyl)phenyl)pyridine (1t)

[0081] Thick liquid, 72% yield; R.sub.f=0.80 (Pet.Ether/EtOAc=95/05); .sup.1H NMR (400 MHz, CDCl.sub.3) =7.70-7.61 (m, 3H), 7.59 (d, J=7.8 Hz, 1H), 7.49-7.39 (m, 2H), 7.38-7.29 (m, 3H), 7.21 (d, J=7.8 Hz, 1H), 6.69 (d, J=7.8 Hz, 1H), 2.47 (s, 3H), 1.69 (s, 9H); 13C NMR (100 MHz, CDCl.sub.3) =163.4, 154.5, 142.1, 138.4, 137.8, 133.2, 131.3, 130.4, 128.6, 128.2, 128.0, 123.7, 118.1, 116.7, 111.7, 91.8, 89.8, 79.4, 77.3, 76.7, 28.9, 21.6; HRMS (ESI) calcd for C.sub.24H.sub.24ON (M.sup.++H) 342.1852, found 342.1851.

k) 2-(tert-butoxy)-6-(5-fluoro-2-(phenylethynyl)phenyl)pyridine (1u)

[0082] Thick liquid, 74% yield; mp=65-66 C.; R.sub.f=0.70 (Pet.Ether/EtOAc=95/05); .sup.1H NMR (400 MHz, CDCl.sub.3) =7.77 (d, J=7.3 Hz, 1H), 7.69-7.57 (m, 3H), 7.51-7.41 (m, 2H), 7.39-7.28 (m, 3H), 7.09 (dt, J=2.4, 8.2 Hz, 1H), 6.71 (d, J=7.9 Hz, 1H), 1.68 (s, 9H); .sup.13C NMR (100 MHz, CDCl.sub.3) =163.7-161.3 (d, J=248.92 Hz), 163.5, 152.8, 144.5-144.4 (d, J=8.48 Hz), 138.0, 135.2-135.1 (d, J=8.48 Hz), 131.3, 128.3, 128.2, 123.3, 117.0 (d, J=3.03 Hz), 116.7-116.4 (d, J=23.12 Hz), 116.5, 115.2-115.0 (d, J=21.58 Hz), 112.4, 92.3, 88.7, 79.6, 28.8; HRMS (ESI) calcd for C.sub.23H.sub.21ONF (M.sup.++H) 346.1602, found 346.1601.

l) 1-methoxy-3-(2-(phenylethynyl)phenyl)isoquinoline (1x)

[0083] During preparation of 1x, the 2-bromo-6-methoxyisoquinoline was used instead of 2-bromo-6-butylypyridine.

[0084] Yellowish solid, 68% yield; mp=84-85 C.; R.sub.f=0.75 (Pet.Ether/EtOAc=95/05); .sup.1H NMR (400 MHz, CDCl.sub.3) =8.35 (d, J=7.6 Hz, 1H), 8.16 (s, 1H), 8.09 (dd, J=1.1, 7.6 Hz, 1H), 7.84 (d, J=8.0 Hz, 1H), 7.77 (dd, J=1.1, 7.6 Hz, 1H), 7.70 (dt, J=1.3, 7.5 Hz, 1H), 7.59 (ddd, J=1.0, 7.0, 8.1 Hz, 1H), 7.54-7.50 (m, 1H), 7.50-7.45 (m, 2H), 7.42 (dt, J=1.3, 7.5 Hz, 1H), 7.36-7.32 (m, 3H), 4.27 (s, 3H); .sup.13C NMR (100 MHz, CDCl.sub.3) =160.2, 147.5, 141.9, 138.2, 133.5, 131.3, 130.4, 129.8, 128.5, 128.3, 128.1, 127.6, 126.6, 126.6, 124.1, 123.6, 121.1, 118.8, 115.0, 92.7, 90.0, 53.7; HRMS (ESI) calcd for C.sub.28H.sub.18ON (M.sup.++H) 336.1383, found 336.1384.

m) 2-(tert-butoxy)-6-(2-((2-chloro-5-methoxyphenyl)ethynyl)phenyl)pyridine (1y)

[0085] Yellowish solid, 52% yield; mp=85-86 C.; R.sub.f=0.60 (Pet.Ether/EtOAc=95/05); .sup.1H NMR (500 MHz, CDCl.sub.3) =7.87 (dd, J=1.1, 8.0 Hz, 1H), 7.75 (d, J=7.2 Hz, 1H), 7.72 (dd, J=1.1, 7.6 Hz, 1H), 7.63-7.57 (m, 1H), 7.48 (dt, J=1.5, 7.6 Hz, 1H), 7.41-7.35 (m, 1H), 7.28 (d, J=8.8 Hz, 1H), 6.96 (d, J=3.1 Hz, 1H), 6.81 (dd, J=3.1, 8.8 Hz, 1H), 6.66 (d, J=8.4 Hz, 1H), 3.79 (s, 3H), 1.65 (s, 9H); .sup.13C NMR (125 MHz, CDCl.sub.3) =163.4, 157.8, 153.9, 142.3, 138.0, 133.7, 129.9, 129.7, 128.9, 127.7, 127.4, 123.9, 120.6, 117.6, 116.9, 116.0, 111.9, 94.3, 89.5, 79.4, 55.5, 28.8; HRMS (ESI) calcd for C.sub.24H.sub.22O.sub.2NCl (M.sup.++H) 392.1412, found 392.1417.

n) 2-(tert-butoxy)-6-(2-((3-chloro-4-methylphenyl)ethynyl)phenyl)pyridine (1z)

[0086] Yellowish solid, 52% yield; mp=81-82 C.; R.sub.f=0.60 (Pet.Ether/EtOAc=95/05); .sup.1H NMR (500 MHz, CDCl.sub.3) =7.67-7.61 (m, 3H), 7.46 (dt, J=1.5, 7.6 Hz, 1H), 7.42 (d, J=1.5 Hz, 1H), 7.37 (dt, J=1.1, 7.4 Hz, 1H), 7.23-7.15 (m, 2H), 6.68 (t, J=4.4 Hz, 1H), 2.39 (s, 3H), 1.66 (s, 9H); 13C NMR (125 MHz, CDCl.sub.3) =163.5, 154.2, 142.3, 137.9, 136.4, 134.2, 133.2, 131.6, 130.8, 129.8, 129.5, 128.6, 127.7, 122.4, 120.7, 116.5, 111.9, 91.2, 90.1, 79.5, 28.9, 20.0; HRMS (ESI) calcd for C.sub.24H.sub.23ONCl (M.sup.++H) 376.1463, found 376.1458.

o) 2-(tert-butoxy)-6-(3,5-dimethoxy-2-(phenylethynyl)phenyl)pyridine (1aa)

[0087] Yellowish solid, 76% yield; mp=124-125 C.; R.sub.f=0.55 (Pet.Ether/EtOAc=95/05); .sup.1H NMR (400 MHz, CDCl.sub.3) =7.70 (d, J=7.8 Hz, 1H), 7.61 (t, J=7.6 Hz, 1H), 7.42 (d, J=6.4 Hz, 2H), 7.35-7.25 (m, 3H), 7.02 (d, J=2.0 Hz, 1H), 6.67 (d, J=8.3 Hz, 1H), 6.53 (d, J=2.0 Hz, 1H), 3.96 (s, 3H), 3.89 (s, 3H), 1.66 (s, 9H); 13C NMR (100 MHz, CDCl.sub.3) =163.2, 161.8, 160.3, 154.1, 145.1, 137.8, 131.2, 128.1, 127.6, 124.1, 116.9, 111.9, 106.0, 98.3, 95.8, 85.6, 79.4, 56.2, 55.3, 28.8; HRMS (ESI) calcd for C.sub.25H.sub.26O.sub.3N (M.sup.++H) 388.1907, found 388.1904.

Example 3: Procedure for Gold-Catalyzed 1,2 amino-oxygenation of alkyne

[0088] To a screw-cap vial containing a stir bar were added 2-(tert-butoxy)-6-(2-(phenylethynyl)phenyl)pyridine (1a) (80 mg, 0.10 mmol), 5 mol % (C.sub.6F.sub.5).sub.3PAuCl (7 mg, 5 mol %) and CH.sub.3CN (2 mL). The reaction vial was fitted with a cap, evacuated and back filled with N.sub.2 and heated at 80 C. for 6 h. When the reaction time was completed, the reaction mixture was allowed to cool at ambient temperature. The mixture was diluted with CH.sub.2Cl.sub.2 (10 mL) and filtered through a Celite pad and the Celite pad was washed several times with CH.sub.2Cl.sub.2 (50 mL). The combined filtrate was concentrated in vacuo and the resulting residue was purified by column chromatography on silica (DCM/MeOH; 95:5) to afford the products. 3a as off white solid in 92% yield.

a) 1-phenylbenzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3a)

[0089] Off white solid, 92% yield; mp=192-193 C.; R.sub.f=0.50 (DCM/MeOH=95/05); .sup.1H NMR (500 MHz, DMSO-d.sub.6) =8.89 (br. s., 2H), 8.83 (d, J=5.9 Hz, 2H), 8.65 (d, J=3.9 Hz, 1H), 8.37 (d, J=7.3 Hz, 2H), 8.16-7.99 (m, 2H), 7.92-7.81 (m, 3H); .sup.13C NMR (100 MHz, DMSO-d.sub.6) =150.4, 146.4, 142.6, 135.8, 133.9, 133.4, 132.7, 131.0, 130.5, 127.6, 127.0, 125.9, 124.6, 121.2, 117.0, 108.6; nB NMR (160 MHz, DMSO-d.sub.6): 1.31; .sup.19F NMR (470 MHz, DMSO-d.sub.6): 148.22, 148.28 and secondary isotopic shift (.sup.10B, .sup.11B) of 0.055 ppm; HRMS (ESI) calcd for C.sub.19H.sub.12ON.sup.+ (M.sup.+-BF.sub.4.sup.) 270.0913, found 270.0910.

b) 1-(naphthalen-1-yl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3b)

[0090] Light yellow solid, 68% yield; mp=198-200 C.; R.sub.f=0.45 (DCM/MeOH=95/05); .sup.1H NMR (500 MHz, DMSO-d.sub.6) =8.95 (s, 1H), 8.84 (d, J=7.6 Hz, 1H), 8.73 (d, J=7.2 Hz, 1H), 8.49-8.37 (m, 3H), 8.28 (d, J=6.5 Hz, 1H), 8.07-7.92 (m, 5H), 7.88-7.77 (m, 3H); .sup.13C NMR (125 MHz, DMSO-d.sub.6) =149.8, 147.0, 142.7, 135.9, 134.1, 133.9, 133.5, 132.5, 130.9, 129.4, 129.3, 128.9, 127.7, 127.2, 126.1, 125.9, 124.6, 124.3, 123.0, 121.4, 117.0, 109.0; HRMS (ESI) calcd for C.sub.23H.sub.14ON.sup.+ (M.sup.+-BF.sub.4.sup.) 320.1070, found 320.1065.

c) 1-(phenanthren-9-yl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3d)

[0091] Light yellow solid, 63% yield; mp=230-232 C.; R.sub.f=0.50 (DCM/MeOH=95/05); .sup.1H NMR (400 MHz, DMSO-d.sub.6) =9.16 (d, J=8.3 Hz, 1H), 9.09-9.04 (m, 1H), 9.01-8.91 (m, 2H), 8.85 (d, J=7.8 Hz, 1H), 8.79 (s, 1H), 8.75 (d, J=7.8 Hz, 1H), 8.50 (d, J=7.8 Hz, 1H), 8.39 (d, J=7.8 Hz, 1H), 8.13-7.93 (m, 5H), 7.87 (q, J=7.5 Hz, 2H); .sup.13C NMR (100 MHz, DMSO-d.sub.6) =153.3, 149.6, 147.0, 142.9, 136.0, 134.2, 133.3, 132.6, 131.5, 130.9, 130.4, 130.3, 130.0, 128.6, 128.4, 128.1, 127.2, 125.9, 125.3, 124.9, 124.3, 123.5, 123.4, 123.2, 122.7, 120.6, 117.1, 115.6, 109.0; HRMS (ESI) calcd for C.sub.27H.sub.16ON.sup.+ (M.sup.+-BF.sub.4.sup.) 370.1225, found 370.1226.

d) 1-(p-tolyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3g)

[0092] Off white solid, 85% yield; mp=222-223 C.; R.sub.f=0.40 (DCM/MeOH=95/05); .sup.1H NMR (500 MHz, DMSO-d.sub.6) =8.92-8.84 (m, 2H), 8.79 (d, J=8.0 Hz, 1H), 8.82 (d, J=8.0 Hz, 1H), 8.65-8.56 (m, 1H), 8.27 (d, J=8.0 Hz, 2H), 8.10 (t, J=7.4 Hz, 1H), 8.05 (t, J=7.6 Hz, 1H), 7.68 (d, J=7.6 Hz, 2H), 2.53 (s, 3H); .sup.13C NMR (100 MHz, DMSO-d.sub.6) =150.8, 146.2, 144.2, 142.2, 135.7, 133.7, 132.6, 131.0, 130.8, 127.6, 127.0, 125.8, 124.4, 121.8, 120.5, 116.9, 108.4, 21.4; HRMS (ESI) calcd for C.sub.20H.sub.14ON.sup.+ (M.sup.+-BF.sub.4.sup.) 284.1070, found 284.1067.

e) 1-(4-isopropylphenyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3h)

[0093] Off white solid, 80% yield; mp=214-215 C.; R.sub.f=0.40 (DCM/MeOH=95/05); .sup.1H NMR (400 MHz, DMSO-d.sub.6) =8.88 (d, J=3.9 Hz, 2H), 8.79 (d, J=7.8 Hz, 1H), 8.82 (d, J=7.8 Hz, 1H), 8.63 (t, J=3.9 Hz, 1H), 8.36-8.23 (m, J=7.3 Hz, 2H), 8.13-8.02 (m, 2H), 7.78-7.70 (m, J=7.8 Hz, 2H), 3.12 (td, J=6.7, 13.6 Hz, 1H), 1.32 (d, J=7.3 Hz, 6H); .sup.13C NMR (125 MHz, DMSO-d.sub.6) =154.5, 150.8, 146.2, 142.3, 135.7, 133.8, 132.6, 130.8, 128.5, 127.9, 127.0, 125.9, 124.4, 122.2, 120.6, 116.9, 108.5, 33.7, 23.4; HRMS (ESI) calcd for C.sub.22H.sub.18ON.sup.+ (M.sup.+-BF.sub.4.sup.) 312.1383, found 312.1382.

f) 1-(4-methoxyphenyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3j)

[0094] Light yellow solid, 83% yield; mp=190-192 C.; R.sub.f.sup.=0.30 (DCM/MeOH=95/10); .sup.1H NMR (400 MHz, DMSO-d.sub.6) =8.94-8.70 (m, 4H), 8.58 (d, J=7.3 Hz, 1H), 8.33 (d, J=8.5 Hz, 2H), 8.12-7.98 (m, 2H), 7.41 (d, J=8.5 Hz, 2H), 3.97 (br. s., 3H); 13C NMR (125 MHz, DMSO-d.sub.6) =163.2, 151.1, 146.0, 141.7, 135.4, 133.5, 132.5, 130.5, 129.9, 127.1, 125.8, 124.0, 119.4, 116.7, 116.1, 108.1, 55.9; HRMS (ESI) calcd for C.sub.20H.sub.14O.sub.2N.sup.+ (M.sup.+-BF.sub.4.sup.) 300.1019, found 300.1019.

g) 1-(4-butoxyphenyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3k)

[0095] Light yellow solid, 86% yield; mp=183-185 C.; R.sub.f=0.30 (DCM/MeOH=95/10); .sup.1H NMR (400 MHz, DMSO-d.sub.6) =8.95-8.71 (m, 4H), 8.64-8.53 (m, 1H), 8.42-8.22 (m, 2H), 8.16-7.99 (m, 2H), 7.42-7.32 (m, 2H), 4.23-4.15 (m, 2H), 1.82-1.74 (m, 2H), 1.54-1.45 (m, 2H), 0.98 (t, J=7.3 Hz, 3H); .sup.13C NMR (100 MHz, DMSO-d.sub.6) =162.8, 151.2, 146.1, 141.7, 135.5, 133.5, 132.6, 130.5, 130.2, 130.0, 127.1, 125.8, 124.0, 119.4, 116.8, 116.5, 108.1, 68.130.6, 18.8, 13.8; HRMS (ESI) calcd for C.sub.23H.sub.20O.sub.2N.sup.+ (M.sup.+-BF.sub.4.sup.) 342.1489, found 342.1483.

h) 1-(4-fluorophenyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3l)

[0096] Off white solid, 71% yield; mp=254-255 C.; R.sub.f=0.60 (DCM/MeOH=95/10); .sup.1H NMR (400 MHz, DMSO-d.sub.6) =8.98-8.75 (m, 3H), 8.64 (d, J=8.3 Hz, 1H), 8.54-8.37 (m, 2H), 8.22-8.01 (m, 2H), 7.85-7.62 (m, 3H); .sup.13C NMR (100 MHz, DMSO-d.sub.6) =166.2, 165.9-163.4 (d, J=254.31 Hz), 153.1, 151.3, 149.5, 146.3, 143.7, 142.7, 135.8, 133.9, 132.9, 132.6, 131.6, 131.0, 130.9-130.8 (d, J=9.25 Hz), 130.7-130.6 (d, J=10.02 Hz), 126.9, 126.3, 126.0, 124.7, 124.4, 121.8, 121.3, 121.0, 118.2-118.0 (d, J=23.12 Hz), 118.1-117.9 (d, J=22.35 Hz), 117.1, 110.4-110.3 (d, J=6.94 Hz), 108.6; HRMS (ESI) calcd for C.sub.19H.sub.11ONF.sup.+ (M.sup.+-BF.sub.4.sup.) 288.0819, found 288.0815.

i) 1-(4-chlorophenyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3m)

[0097] Off white solid, 65% yield; mp=274-275 C.; R.sub.f=0.60 (DCM/MeOH=95/10); .sup.1H NMR (400 MHz, DMSO-d.sub.6) =8.99-8.86 (m, 2H), 8.79 (d, J=7.3 Hz, 1H), 8.83 (d, J=7.8 Hz, 1H), 8.65 (d, J=6.8 Hz, 1H), 8.37 (d, J=8.3 Hz, 2H), 8.17-8.02 (m, 2H), 7.92 (d, J=8.3 Hz, 2H); .sup.13C NMR (100 MHz, DMSO-d.sub.6) =149.3, 146.4, 142.9, 138.0, 135.9, 134.0, 132.7, 131.2, 130.7, 129.4, 126.8, 126.0, 124.6, 123.4, 121.5, 117.1, 108.8; HRMS (ESI) calcd for C.sub.19H.sub.11ONCl.sup.+ (M.sup.+-BF.sub.4.sup.) 304.0524, found 304.0520.

j) 1-(4-(dimethylamino)phenyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3n)

[0098] Reddish solid, 82% yield; mp=242-244 C.; R.sub.f=0.5 (DCM/MeOH=95/10); .sup.1H NMR (400 MHz, DMSO-d.sub.6) =8.78 (d, J=6.8 Hz, 2H), 8.75-8.61 (m, 2H), 8.45 (d, J=8.3 Hz, 1H), 8.21-8.10 (m, J=8.8 Hz, 2H), 8.05 (t, J=7.1 Hz, 1H), 7.97 (d, J=7.3 Hz, 1H), 7.13-6.93 (m, J=8.3 Hz, 2H), 3.18-3.13 (m, 6H); 13C NMR (125 MHz, DMSO-d.sub.6) =153.1, 152.9, 145.5, 139.8, 134.5, 132.5, 132.1, 129.5, 129.3, 127.2, 125.5, 123.3, 116.7, 116.2, 112.7, 110.0, 106.8, 40.1; HRMS (ESI) calcd for C.sub.21H.sub.17ON.sub.2.sup.+ (M.sup.+-BF.sub.4.sup.) 313.1335, found 313.1330.

k) 1-(4-pentanoylphenyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3o)

[0099] Off white solid, 53% yield; mp=202-204 C.; R/=0.30 (DCM/MeOH=95/05); .sup.1H NMR (500 MHz, DMSO-d.sub.6) =9.00 (t, J=9.5 Hz, 1H), 8.93 (d, J=7.9 Hz, 1H), 8.81 (dd, J=2.4, 9.2 Hz, 1H), 8.66 (d, J=7.9 Hz, 1H), 8.51 (d, J=8.5 Hz, 2H), 8.41-8.35 (m, 2H), 8.19 (t, J=7.6 Hz, 1H), 8.12 (t, J=7.7 Hz, 1H), 3.17 (t, J=7.3 Hz, 2H), 1.67 (quin, J=7.4 Hz, 2H), 1.43-1.37 (m, 2H), 0.95 (t, J=7.4 Hz, 3H); .sup.13C NMR (125 MHz, DMSO-d.sub.6) =199.4, 150.8, 143.9, 139.7, 133.0, 131.9, 131.8, 131.6, 129.7, 128.1, 127.8, 126.4, 126.1, 125.0, 124.1, 123.3, 110.7, 110.7, 38.1, 25.8, 21.8, 13.9; HRMS (ESI) calcd for C.sub.24H.sub.20O.sub.2N.sup.+ (M.sup.+-BF.sub.4.sup.) 354.1489, found 354.1485.

1) 1-(2-methoxyphenyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3p)

[0100] Light yellow solid, 72% yield; mp=228-229 C.; R.sub.f=0.50 (DCM/MeOH=95/10); .sup.1H NMR (400 MHz, DMSO-d.sub.6) =8.92-8.81 (m, 2H), 8.78 (d, J=7.3 Hz, 1H), 8.59 (dd, J=3.7, 5.5 Hz, 1H), 8.33 (d, J=7.9 Hz, 1H), 8.13 (d, J=7.9 Hz, 1H), 8.11-8.03 (m, 1H), 8.03-7.94 (m, 1H), 7.84 (t, J=7.9 Hz, 1H), 7.53 (d, J=8.5 Hz, 1H), 7.38 (t, J=7.6 Hz, 1H), 4.14 (s, 3H); .sup.13C NMR (100 MHz, DMSO-d.sub.6) =157.5, 147.4, 146.3, 142.2, 135.8, 135.3, 133.9, 132.3, 130.2, 129.9, 128.4, 126.9, 125.4, 121.8, 116.5, 113.6, 112.9, 108.2, 56.5; HRMS (ESI) calcd for C.sub.20H.sub.14O.sub.2N.sup.+ (M.sup.+-BF.sub.4.sup.) 300.1019, found 300.1017.

m) 1-(3-methoxyphenyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3q)

[0101] Light yellow solid, 82% yield; mp=206-208 C.; R.sub.f.sup.=0.60 (DCM/MeOH=95/10); .sup.1H NMR (400 MHz, DMSO-d.sub.6) =8.99-8.69 (m, 4H), 8.64 (br. s., 1H), 8.23-8.02 (m, 2H), 7.97 (d, J=7.3 Hz, 1H), 7.86-7.65 (m, 2H), 7.52-7.28 (m, 1H), 3.99 (br. s., 3H); .sup.13C NMR (100 MHz, DMSO-d.sub.6) =160.3, 150.1, 146.3, 142.7, 135.8, 134.0, 132.8, 132.0, 131.1, 126.9, 126.0, 125.8, 124.5, 120.5, 120.3, 119.9, 119.5, 117.0, 111.8, 108.7, 55.8; HRMS (ESI) calcd for C.sub.20H.sub.14O.sub.2N.sup.+ (M.sup.+-BF.sub.4.sup.) 300.1019, found 300.1017.

n) 1-(3-chlorophenyl)benzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3r)

[0102] Off white solid, 58% yield; mp=204-206 C.; R.sub.f=0.30 (DCM/MeOH=95/05); .sup.1H NMR (400 MHz, DMSO-d.sub.6) =8.99 (t, J=9.5 Hz, 1H), 8.83 (d, J=7.8 Hz, 1H), 8.77 (d, J=8.8 Hz, 1H), 8.65 (d, J=7.3 Hz, 1H), 8.45-8.27 (m, 2H), 8.18 (t, J=7.6 Hz, 1H), 8.11 (t, J=7.6 Hz, 1H), 7.93 (q, J=7.8 Hz, 2H); .sup.13C NMR (100 MHz, DMSO-d.sub.6) =150.7, 150.3, 143.8, 135.1, 133.4, 133.0, 132.6, 131.9, 131.7, 131.5, 126.9, 126.7, 126.4, 126.2, 126.0, 125.0, 122.9, 110.7, 110.6; HRMS (ESI) calcd for C.sub.19H.sub.11ONCl.sup.+ (M.sup.+-BF.sub.4.sup.) 304.0524, found 304.0521.

o) 6-methyl-1-phenylbenzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3s)

[0103] Off white solid, 85% yield; mp=220-221 C.; R.sub.f=0.30 (DCM/MeOH=95/05); .sup.1H NMR (500 MHz, DMSO-d.sub.6) =8.88 (t, J=8.2 Hz, 1H), 8.78 (d, J=7.6 Hz, 1H), 8.66 (d, J=8.4 Hz, 2H), 8.36 (d, J=7.2 Hz, 2H), 8.01 (t, J=7.8 Hz, 1H), 7.91-7.80 (m, 4H), 2.99 (s, 3H); .sup.13C NMR (125 MHz, DMSO-d.sub.6) =150.2, 146.4, 142.5, 137.9, 135.6, 133.3, 132.7, 132.6, 132.4, 130.5, 127.6, 127.0, 124.6, 122.1, 121.3, 118.4, 108.4, 19.4; HRMS (ESI) calcd for C.sub.20H.sub.14ON.sup.+ (M.sup.+-BF.sub.4.sup.) 284.1070, found 284.1067.

p) 7-methyl-1-phenylbenzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3t)

[0104] Off white solid, 76% yield; mp=224-226 C.; R.sub.f=0.40 (DCM/MeOH=95/05); .sup.1H NMR (500 MHz, DMSO-d.sub.6) =8.89 (t, J=8.2 Hz, 1H), 8.78 (d, J=7.6 Hz, 1H), 8.66 (d, J=8.4 Hz, 2H), 8.36 (d, J=7.2 Hz, 2H), 8.01 (t, J=7.8 Hz, 1H), 7.90-7.82 (m, 4H), 2.99 (s, 3H); 13C NMR (125 MHz, DMSO-d.sub.6) =149.8, 146.4, 142.6, 141.6, 135.8, 134.2, 133.6, 133.2, 130.5, 127.5, 126.0, 124.7, 124.6, 124.2, 121.1, 116.8, 108.5, 21.5; HRMS (ESI) calcd for C.sub.20H.sub.14ON.sup.+ (M.sup.+-BF.sub.4.sup.) 284.1070, found 284.1067.

q) 7-fluoro-1-phenylbenzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3u)

[0105] Off white solid, 65% yield; mp=255-256 C.; R.sub.f=0.60 (DCM/MeOH=95/10); .sup.1H NMR (400 MHz, DMSO-d.sub.6) =9.02-8.84 (m, 3H), 8.80 (dd, J=2.1, 8.9 Hz, 1H), 8.70 (d, J=8.5 Hz, 1H), 8.46-8.29 (m, 2H), 7.98 (dt, J=2.4, 8.9 Hz, 1H), 7.92-7.76 (m, 3H); .sup.13C NMR (100 MHz, DMSO-d.sub.6) =164.2-161.7 (d, J=250.16 Hz), 150.3, 146.3, 142.6, 135.9, 135.8, 135.1-135.1 (d, J=3.83 Hz), 133.4, 130.5, 127.6, 126.7-126.6 (d, J=9.59 Hz), 124.4, 123.6, 120.5, 120.5-120.2 (d, J=23.96 Hz), 117.7, 113.2-112.9 (d, J=25.88 Hz), 109.3; HRMS (ESI) calcd for C.sub.19H.sub.11ONF.sup.+ (M.sup.+-BF.sub.4.sup.) 288.0819, found 288.0815.

r) 7-chloro-1-phenylbenzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3v)

[0106] off white solid, 56% yield; mp=208-210 C.; R.sub.f=0.35 (DCM/MeOH=95/05); .sup.1H NMR (400 MHz, DMSO-d.sub.6) =9.09-8.80 (m, 4H), 8.68 (d, J=3.4 Hz, 1H), 8.39 (d, J=6.8 Hz, 2H), 8.16 (d, J=8.3 Hz, 1H), 7.87 (d, J=6.4 Hz, 3H); .sup.13C NMR (100 MHz, DMSO-d.sub.6) =150.8, 146.3, 142.8, 140.9, 135.6, 135.3, 134.8, 133.6, 132.4, 130.5, 128.0, 127.8, 125.9, 125.6, 124.4, 120.6, 117.7, 109.4; HRMS (ESI) calcd for C.sub.19H.sub.11ONCl.sup.+ (M.sup.+-BF.sub.4.sup.) 304.0524, found 304.0517.

s) 8-chloro-1-phenylbenzo[a]oxazolo[4,3,2-cd]indolizin-10-ium tetrafluoroborate (3w)

[0107] Off white solid, 52% yield; mp=206-208 C.; R.sub.f=0.30 (DCM/MeOH=95/05); .sup.1H NMR (400 MHz, DMSO-d.sub.6) =8.99-8.78 (m, 4H), 8.68 (d, J=3.4 Hz, 1H), 8.39 (d, J=6.8 Hz, 2H), 8.16 (d, J=8.3 Hz, 1H), 7.87 (d, J=6.4 Hz, 3H); .sup.13C NMR (100 MHz, DMSO-d.sub.6) =151.3, 146.3, 142.8, 137.7, 135.0, 133.7, 132.5, 131.2, 130.6, 128.4, 128.1, 127.3, 124.3, 120.4, 117.3, 108.9; HRMS (ESI) calcd for C.sub.19H.sub.11ONCl.sup.+ (M.sup.+-BF.sub.4.sup.) 304.0524, found 304.0533.

t) 1-phenyldibenzo[a,f]oxazolo[4,3,2-cd]indolizin-12-ium tetrafluoroborate (3x)

[0108] White solid, 72% yield; mp=258-259 C.; R.sub.f=0.5 (DCM/MeOH=95/10); .sup.1H NMR (500 MHz, DMSO-d.sub.6) =9.30 (s, 1H), 9.06 (d, J=8.0 Hz, 1H), 8.81-8.77 (m, 1H), 8.77-8.73 (m, 1H), 8.69 (d, J=8.4 Hz, 1H), 8.45-8.42 (m, 2H), 8.35-8.30 (m, 1H), 8.30-8.24 (m, 1H), 8.09-8.01 (m, 2H), 7.90-7.86 (m, 2H), 7.82 (d, J=7.2 Hz, 1H); .sup.13C NMR (125 MHz, DMSO-d.sub.6) =148.3, 145.7, 138.1, 134.4, 134.1, 132.6, 132.1, 131.4, 130.6, 130.4, 129.7, 127.1, 127.0, 126.9, 125.3, 124.8, 124.8, 123.6, 122.0, 116.7, 113.9; HRMS (ESI) calcd for C.sub.23H.sub.14ON.sup.+ (M.sup.+-BF.sub.4.sup.) 320.1070, found 320.1071.

u) 6-(2-chloro-5-methoxyphenyl)-4H-pyrido[2,1-a]isoquinolin-4-one (3y)

[0109] Yellow solid, 62% yield; mp=186-187 C.; R.sub.f=0.40 (Pet. Ether/EtOAc=70/30); .sup.1H NMR (500 MHz, CDCl.sub.3) =7.89 (d, J=7.6 Hz, 1H), 7.76 (d, J=7.2 Hz, 1H), 7.56-7.47 (m, 2H), 7.41 (dd, J=6.9, 8.8 Hz, 1H), 7.34-7.28 (m, 2H), 6.83 (dd, J=3.1, 8.8 Hz, 1H), 6.74 (d, J=6.5 Hz, 1H), 6.60 (d, J=2.7 Hz, 1H), 6.49 (d, J=9.2 Hz, 1H), 3.75 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) =159.7, 156.4, 145.0, 137.7, 136.4, 135.6, 134.8, 130.5, 130.0, 129.2, 128.5, 125.5, 120.5, 120.3, 119.7, 116.5, 114.7, 112.2, 99.0, 55.4; HRMS (ESI) calcd for C.sub.20H.sub.15O.sub.2NCl (M.sup.++H) 336.0784, found 336.0779.

v) (E)-6-(3-chloro-4-methylbenzylidene)pyrido[2,1-a]isoindol-4(6H)-one (3z)

[0110] Yellow solid, 23% yield; mp=194-195 C.; R.sub.f=0.35 (Pet. Ether/EtOAc=60/20); .sup.1H NMR (500 MHz, CDCl.sub.3) =9.34 (s, 1H), 7.54 (s, 1H), 7.51-7.42 (m, 6H), 7.40 (d, J=7.2 Hz, 1H), 7.14 (d, J=8.4 Hz, 1H), 7.02 (d, J=8.0 Hz, 1H), 6.76 (d, J=6.5 Hz, 1H), 6.64 (d, J=9.2 Hz, 1H), 2.42 (s, 3H); .sup.13C NMR (125 MHz, CDCl.sub.3) =163.0, 143.9, 139.5, 137.9, 137.6, 135.9, 131.9, 131.0, 130.0, 129.1, 128.7, 127.9, 123.8, 123.2, 120.5, 120.1, 98.5, 21.6; HRMS (ESI) calcd for C.sub.20H.sub.14ONCl (M.sup.++H) 319.0680, found 319.0675.

Example 4: Bioimaging Studies of Pyridinium-Oxazole Dyad Salt 3n in MCF-7 Cells

[0111] Materials:

[0112] MCF-7 cells are obtained from National Centre for Cell Science, Pune, India. Dulbecco's modified eagle medium (DMEM), Dulbecco's phosphate buffered saline (DPBS), fetal bovine serum (FBS), MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and DAPI are purchased from Sigma-Aldrich, USA.

[0113] Sample Preparation for In Vitro Studies:

[0114] The stock solutions (5 mM) of the organic molecules are prepared in DMSO solvent. Each time, the freshly prepared stock solutions are used for all the cell culture experiments.

[0115] Cell Culture:

[0116] MCF-7 cells were obtained from National Centre for Cell Science, Pune, India. For bio imaging purpose, the cells were seeded in a 6 well plate at a density of 10.sup.5 cells/mL in Dulbecco's Modified Eagle's Medium+Ham's F12 containing 10% fetal bovine serum and a 0.1% antibiotic solution for 24 h at 370 C and 5% CO2 for adherence

[0117] Cell Viability Assay:

[0118] Cell viability assay was performed in MCF-7 cells using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) reagent. Compounds at concentration of 1, 5, 10 and 20 M dissolved in DMSO were added to the cells in media without FBS. DMSO was used as a control. MTT assay was carried out after 24 h incubation. A MTT solution (20 l, 5 mg/mL) was prepared in PBS pH 7.4 then added to each well and incubated for 3 h. The purple formazan crystals formed were dissolved by addition of 150 l of DMSO for 5 min absorbance was measured using Biotek SYNERGY HT, microplate reader. IC.sub.50 was determined by using ED50V10 excel add-on software. Finally, the absorbance of solution was measured using a multimode reader (Biotek Synergy) at 570 nm.

[0119] In Vitro Imaging:

[0120] MCF-7 cells (110.sup.4 cells/mL/well) were seeded in a 6-well tissue culture plate for 48 h. The cells were then treated with 1 M concentration of different organic molecules for 30 minutes. After thorough washing with 1PBS (P.sup.H 7.4), the cells are fixed used paraformaldehye (4% in PBS) for 15 minutes. Then cells were washed using 1PBS twice. Further cells are permeated using 0.4% triton X in PBS for 30 seconds followed by treatment with 1 g/mL of DAPI solution for 15 minutes. The cells are again ished twice with 1PBS (P.sup.H 7.4). Finally, a confocal fluorescence microscope (Nikon Eclipse: TE 2000-E, Japan). Bioimaging studies are carried out using red and green filters. (FIG. 2)

Example 5: Co-Staining Experiment with Standard Mitotracker Green (MG)

[0121] Cells are cultured and maintained as described above. Cells were treated with 1 M compound for 30 min followed by washing with PBS. Further cells were treated with 50 nm MG for 10 min and then washed with PBS. Cells were fixed and treated with DAPI as described above.

Example 6: Assessment of 3n for its Ability to Localize and Stain Mitochondria in Living Cells

[0122] MCF-7 cells were incubated with 1 M of 3n for 1 h, and excess dyes were washed away by buffer solution. As shown in FIG. 2 (a1 and b1), 3n stains specifically the mitochondrial region in MCF-7 cells. The costaining experiment with MitoTracker green MG (MT), a commercially available mitochondria imaging agent, suggests that the observed fluorescence from 3n is localized in the mitochondria of the living MCF-7 cells (FIG. 2). This study suggests that the 3n can successfully be exploited as an imaging agent for mitochondrial targeting.

Advantages of the Invention

[0123] 1. This is first method for preparation of pyridinium-oxazole dyad salts.

[0124] 2. These are new class of fluorescent molecules.

[0125] 3. These class of molecules can be used as mitochondria tracker in live cells.

[0126] 4. These ionic salts can be used as dopants in organic light emitting diods cells.