Alpha, Beta-UNSATURATED AMIDE COMPOUND, AND PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
20250313539 ยท 2025-10-09
Inventors
- Hong Liu (Shanghai, CN)
- Lin XU (Kunming, Yunnan, CN)
- Yu Zhou (Shanghai, CN)
- Yahong TAN (Kunming, Yunnan, CN)
- Yibing Wang (Shanghai, CN)
- Jinnan LI (Kunming, Yunnan, CN)
- He HUANG (Shanghai, CN)
- Qixin ZHOU (Kunming, Yunnan, CN)
- Yilang CHENG (Shanghai, CN)
- Hualiang Jiang (Shanghai, CN)
Cpc classification
C07D413/10
CHEMISTRY; METALLURGY
A61K31/427
HUMAN NECESSITIES
C07D263/26
CHEMISTRY; METALLURGY
A61P9/10
HUMAN NECESSITIES
C07D233/80
CHEMISTRY; METALLURGY
A61K31/4439
HUMAN NECESSITIES
A61K31/422
HUMAN NECESSITIES
A61K31/4709
HUMAN NECESSITIES
A61P25/28
HUMAN NECESSITIES
C07D417/06
CHEMISTRY; METALLURGY
C07D263/52
CHEMISTRY; METALLURGY
C07D413/06
CHEMISTRY; METALLURGY
C07D263/22
CHEMISTRY; METALLURGY
International classification
C07D263/26
CHEMISTRY; METALLURGY
C07D413/06
CHEMISTRY; METALLURGY
A61K31/422
HUMAN NECESSITIES
C07D413/10
CHEMISTRY; METALLURGY
A61K31/4439
HUMAN NECESSITIES
A61K31/4709
HUMAN NECESSITIES
C07D417/06
CHEMISTRY; METALLURGY
A61K31/427
HUMAN NECESSITIES
C07B59/00
CHEMISTRY; METALLURGY
C07D233/80
CHEMISTRY; METALLURGY
Abstract
Provided in the present invention are an ,-unsaturated amide compound, and a preparation method therefor, and a pharmaceutical composition and the use thereof. Specifically, provided in the present invention is a compound as represented by formula I, wherein the definition of each group is as described in the description. The compound can be used as a compound for improving cerebral blood flow and is used for preparing a pharmaceutical composition for treating neurodegenerative diseases such as Alzheimer's disease and vascular dementia and strokes.
Claims
1. An ,-unsaturated amide compound of formula I, or a racemic, a R-isomer, a S-isomer, a pharmaceutically acceptable salt, or a mixture thereof: ##STR00006## wherein, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 can each be independently selected from the group consisting of hydrogen, deuterium, tritium, halogen, cyano, amino, hydroxyl, nitro, substituted or unsubstituted C1C6 alkyl, substituted or unsubstituted C1C6 alkoxy and (CHR.sup.6).sub.nR; wherein R is selected from the group consisting of: substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted 5-7 membered heteroaryl, substituted or unsubstituted 5-7 membered heterocyclyl, substituted or unsubstituted C3-C12 cycloalkyl or fused heterocycle; or R.sup.3 and R.sup.4 together with the attached carbon atom form a group selected from the group consisting of carbonyl, substituted or unsubstituted 3-8-membered cycloalkyl, or substituted or unsubstituted 4-8 membered heterocyclyl; {circle around (A)} ring is selected from the group consisting of: C6-C10 aryl, 5-12 membered heteroaryl, 5-12 membered heterocyclyl, C3-C12cycloalkyl or fused heterocycle; R.sup.5 is 1, 2, 3, 4 or 5 substituents located on {circle around (A)} ring selected from the group consisting of hydrogen, deuterium, tritium, halogen, cyano, amino, hydroxyl, nitro, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted C6-C10 aryloxy, substituted or unsubstituted 5-7 membered heteroaryl, substituted or unsubstituted 5-7 membered heteroaryloxy, substituted or unsubstituted 5-7 membered heterocycle, and substituted or unsubstituted C3-C12 cycloalkyl; or two adjacent R.sup.5 are connected end-to-end with the atoms on {circle around (A)} ring to form a substituted or unsubstituted 4-8 membered ring (i.e., forming a fused ring structure with the A ring); or two R.sup.5 on the same atom of {circle around (A)} ring are connected end-to-end together with {circle around (A)} ring form a substituted or unsubstituted 3-8-membered ring (i.e., forming a spiro ring structure with ring A); X is N(CH.sub.2).sub.nR.sup.6, O, or S; n is 0, 1, 2, or 3; R.sup.6 is independently selected from the group consisting of: hydrogen, halogen, cyano, amino, hydroxyl, nitro, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted 5-12 membered heterocyclyl containing 1 to 3 heteroatoms selected from oxygen, sulfur, and nitrogen, substituted or unsubstituted C2-C10 acyl, substituted or unsubstituted C2-C10 ester group, substituted or unsubstituted C1-C6 amide group, S02R.sup.5, and COR.sup.5; wherein, unless otherwise specified, the heteroaromatic ring, heterocycle, or heterocyclyl are each independently contains 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen; the aromatic or heteroaromatic ring includes a monocyclic, fused-ring, or fused ring, and the carbocycle or heterocycle includes a monocyclic, fused, spiro, or bridged ring; the substituted refers to being substituted by one or more (preferably 1-3) substituents selected from the group consisting of halogen, cyano, nitro, amino, hydroxyl, hydroxymethyl, carboxyl, thiol, C1-C6 alkyl, halogen substituted C1-C6 alkyl, C1-C6 alkoxy, halogen substituted C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, C1-C6 alkylsulfonyl, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted 5-7 membered heteroaryl, and 3-12 membered heterocyclyl; the halogen is F, Cl, Br or I.
2. The ,-unsaturated amide compound according to claim 1, wherein {circle around (A)} ring is selected from the group consisting of C6C10 aryl and C5C12 heteroaryl.
3. The ,-unsaturated amide compound according to claim 1, wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are each independently selected from the group consisting of hydrogen, deuterium, substituted or unsubstituted C1-C6 alkyl and (CHR.sup.6).sub.nR; wherein R is selected from the group consisting of: substituted or unsubstituted C6-C10 aryl, and substituted or unsubstituted 5-7 membered heteroaryl; n is 0, 1, or 2; R.sup.6 is hydrogen, halogen, or substituted or unsubstituted C1-C6 alkyl.
4. The ,-unsaturated amide compound according to claim 1, wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are each independently selected from the group consisting of hydrogen, deuterium, substituted or unsubstituted C1-C6 alkyl and (CHR.sup.6).sub.nR; wherein, R is selected from the group consisting of: substituted or unsubstituted C6-C10 aryl and substituted or unsubstituted 5-7 membered heteroaryl.
5. The ,-unsaturated amide compound according to claim 1, wherein R.sup.1 is H or D, and R.sup.2 is selected from the group consisting of hydrogen, deuterium, substituted or unsubstituted C1-C6 alkyl and (CHR.sup.6).sub.nR; wherein R is selected from the group consisting of: substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted 5-7 membered heteroaryl; the substituted refers to being substituted by one or more substituents selected from the group consisting of halogen, cyano, nitro, amino, hydroxyl, hydroxymethyl, carboxyl, thiol, C1-C6 alkyl, halogen substituted C1-C6 alkyl, C1-C6 alkoxy, halogen substituted C1-C6 alkoxy, and C1-C6 alkoxycarbonyl.
6. The ,-unsaturated amide compound according to claim 1, wherein R.sup.3 and R.sup.4 are each independently deuterium.
7. The ,-unsaturated amide compound according to claim 1, wherein the compound of formula I is selected from the following table: TABLE-US-00003 number structure name 1
8. The preparation method of compound of formula I according to claim 1, wherein the method comprises steps of: ##STR00129## In an inert solvent, reacting a compound of formula II and a compound of formula III to obtain compound of formula I.
9. A pharmaceutical composition, comprising (1) a compound according to claim 1, or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a hydrate or a solvate thereof; and (2) a pharmaceutically acceptable carrier.
10. A use of the compound according to claim 1, or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a hydrate or a solvate thereof, or the pharmaceutical composition comprising the compound according to claim 1, or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, a hydrate of a solvate thereof, in the preparation of a pharmaceutical composition for the prevention and/or treatment of neurodegenerative diseases or stroke; preferably, the neurodegenerative disease is selected from the group consisting of Alzheimer's disease and vascular dementia.
Description
FIGURES
[0038]
[0039]
EXAMPLES
[0040] After long-term and in-depth research, the inventor has provided an , unsaturated amide compound that can be used for neurodegenerative diseases such as Alzheimer's disease. The compound can effectively improve capillary cerebral blood flow. Based on the above findings, the inventor has completed the present invention.
Term
[0041] In the present invention, the halogen is F, Cl, Br, or I.
[0042] In the present invention, unless otherwise specified, the terms used herein have general meanings known to those skilled in the art.
[0043] In the present invention, the term C1-C6 alkyl refers to straight or branched alkyl having 1 to 6 carbon atoms, including but not limited to methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec butyl, tert butyl, pentyl, and hexyl, etc; Preferred is ethyl, propyl, isopropyl, butyl, isobutyl, sec butyl, and tert butyl.
[0044] In the present invention, the term C1-C6 alkoxy refers to straight or branched chain alkoxy having 1 to 6 carbon atoms, including but not limited to methoxy, ethoxy, propoxy, isopropoxy, and butoxy.
[0045] In the present invention, the term C2-C6 alkenyl refers to a straight or branched chain alkenyl containing one double bond with 2 to 6 carbon atoms, including but not limited to vinyl, propenyl, butenyl, isobutenyl, pentenyl, and hexenyl.
[0046] In the present invention, the term C2-C6 alkynyl refers to a straight or branched chain alkynyl containing a triple bond with 2 to 6 carbon atoms, including but not limited to ethynyl, propynyl, butynyl, isobutyl, pentynyl, and hexynyl.
[0047] In the present invention, the term C3-C10 cycloalkyl refers to a cycloalkyl having 3 to 10 carbon atoms on the ring, including but not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and cyclodecyl. The terms C3-C8 cycloalkyl , C3-C7 cycloalkyl , and C3-C6 cycloalkyl have similar meanings.
[0048] In the present invention, the term C3-C10 cycloalkenyl refers to a cycloalkenyl having 3 to 10 carbon atoms on the ring, including but not limited to cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, and cyclodecyl. The term C3-C7 cycloalkenyl has a similar meaning.
[0049] In the present invention, the terms aromatic ring or aryl have the same meaning, and preferably aryl is C6-C12 aryl or C6-C10 aryl. The term C6-C12 aryl refers to aromatic ring groups with 6 to 12 carbon atoms that do not contain heteroatoms on the ring, such as phenyl, naphthyl, etc. The term C6-C10 aryl has a similar meaning.
[0050] In the present invention, the terms aromatic heterocycle or heteroaryl have the same meaning, referring to a heteroaromatic group containing one or more heteroatoms. The heteroatoms referred to here include oxygen, sulfur, and nitrogen. For example, furyl, thienyl, pyridyl, pyrazolyl pyrazole, pyrrolyl, N-alkylpyrrolyl, pyrimidinyl, pyrazinyl, imidazolyl, tetrazolyl, etc. The heteroaromatic ring can be fused onto an aryl, heterocyclyl, or cycloalkyl ring, wherein the ring connected to the parent structure is a heteroaromatic ring. Heteroaryl can be optionally substituted or unsubstituted.
[0051] In the present invention, the term 3-12 membered heterocyclyl refers to a saturated or unsaturated 3-12 membered ring group containing 1-3 heteroatoms selected from oxygen, sulfur, and nitrogen on the ring, such as dioxolane. The term 3-7 membered heterocyclyl has a similar meaning.
[0052] In the present invention, the term substituted refers to one or more hydrogen atoms on a specific functional group are substituted by a specific substituent. The specific substituents were those described in the preceding text or those that appear in various Examples. Unless otherwise specified, a substituted group may have a substituent selected from a specific group at any substitutable site of the group, which may be the same or different at each position. A cyclic substituent, such as a heterocycloalkyl, can be attached to another ring, such as a cycloalkyl, to form a spirobicyclic system, for example, where two rings share a common carbon atom. Those skilled in this field should understand that the expected combinations of substituents in the present invention were those that were stable or chemically achievable. The substituents include (but are not limited to): C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, 3- to 12 membered heterocyclyl, aryl, heteroaryl, halogen, hydroxyl, carboxyl (COOH), C1-8 aldehyde, C2-10 acyl, C2-10 ester group, amino, alkoxy, C1-10 sulfonyl, etc.
Compound of Formula I
[0053] The present invention provides an ,-unsaturated amide compound of Formula I, or a racemic, a R-isomer, a S-isomer, a pharmaceutically acceptable salt, or a mixture thereof:
##STR00003## [0054] wherein, [0055] R.sup.1, R.sup.2, R.sup.3, and R.sup.4 can each be independently selected from the group consisting of hydrogen, deuterium, tritium, halogen, cyano, amino, hydroxyl, nitro, substituted or unsubstituted C1C6 alkyl, substituted or unsubstituted C1C6 alkoxy, and (CHR.sup.6).sub.nR; wherein R is selected from the group consisting of: substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted 5-7 membered heteroaryl, substituted or unsubstituted 5-7 membered heterocyclyl, substituted or unsubstituted C3-C12cycloalkyl or fused heterocycle; [0056] {circle around (A)} ring is selected from the group consisting of: C6-C10 aryl, 5-12 membered heteroaryl, 5-12 membered heterocyclyl, C3-C12cycloalkyl or heterocycle; [0057] R.sup.5 is 1, 2, 3, 4 or 5 substituents located on A ring selected from the group consisting of hydrogen, deuterium, tritium, halogen, cyano, amino, hydroxyl, nitro, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted C6-C10 aryloxy, substituted or unsubstituted 5-7 membered heteroaryl, substituted or unsubstituted 5-7 membered heteroaryloxy, substituted or unsubstituted 5-7 membered heterocycle, substituted or unsubstituted C3-C12 cycloalkyl; [0058] or two adjacent R.sup.5 are connected end-to-end with the atoms on {circle around (A)} ringform a substituted or unsubstituted 4-8 membered ring (i.e., forming a fused ring structure with the A ring); [0059] or two R.sup.5 on the same atom on {circle around (A)} ring are connected end-to-end together with form a substituted or unsubstituted 3-8-membered ring (i.e., forming a spiro ring structure with ring A); [0060] X is N(CH.sub.2).sub.nR.sup.6, O, or S; [0061] n is 0, 1, 2, or 3; [0062] R.sup.6 is independently selected from the group consisting of: hydrogen, halogen, cyano, amino, hydroxyl, nitro, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted 5-12 membered heterocycle containing 1 to 3 heteroatoms selected from oxygen, sulfur, and nitrogen, substituted or unsubstituted C2-C10 acyl, substituted or unsubstituted C2-C10 ester group, substituted or unsubstituted C1-C6 amide group, SO.sub.2R.sup.5, and COR.sup.5; [0063] wherein, unless otherwise specified, the heteroaromatic ring, heterocycle ring, or heterocyclyl are each independently contains 1 to 4 heteroatoms selected from oxygen, sulfur, and nitrogen; the aromatic or heteroaromatic ring includes a monocyclic, fused-ring, or fused ring, and the carbocycle or heterocycle includes a monocyclic, fused, spiro, or bridged ring; [0064] the substituted refers to being substituted by one or more (preferably 1-3) substituents selected from the group consisting of halogen, cyano, nitro, amino, hydroxyl, hydroxymethyl, carboxyl, thiol, C1-C6 alkyl, halogen substituted C1-C6 alkyl, C1-C6 alkoxy, halogen substituted C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, C1-C6 alkylsulfonyl, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted 5-7 membered heteroaryl, and 3-12 membered heterocyclyl; the halogen is F, Cl, Br or I.
[0065] In a preferred embodiment, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, {circle around (A)} ring, X, O, S, or n are each independently the corresponding group in the compound in each example.
Preparation Method for Compound of Formula I
[0066] The present invention also provides a method for preparing a compound represented by formula I, which is carried out according to the following scheme (example):
[0067] The compound of formula (I) can be prepared by the method shown in Scheme 1 below
[0068] The structural formulas and R group labels used in the following schemes were only used in this section. The compounds of formula (II) and formula (III) can be obtained on the market or synthesized using conventional techniques in this field.
##STR00004##
Pharmaceutical Composition
[0069] Another aspect of the present invention provides a pharmaceutical composition comprising a therapeutic effective amount selected from one or more of a compound of Formula I, a pharmaceutically acceptable salt, a enantiomer, a diastereomer, and a racemate, and optionally, one or more pharmaceutically acceptable carriers, excipients, adjuvants, accessories and/or diluents. The accessories can be, such as odorants, fragrances, sweeteners, etc.
[0070] The pharmaceutical composition provided by the present invention preferably contains active ingredients in a weight ratio of 1-99%. The preferred ratio is that the compound of formula I as the active ingredient accounts for 65 wt % to 99 wt % of the total weight, and the remaining part is a pharmaceutically acceptable carrier, diluent, solution or salt solution.
[0071] The compound and pharmaceutical composition provided by the present invention can be various forms, such as tablets, capsules, powders, syrups, solutions, suspensions, and aerosols, and can be present in suitable solid or liquid carriers or diluents and in suitable disinfectants for injection or drip.
[0072] The various dosage forms of the pharmaceutical composition of the present invention can be prepared according to conventional preparation methods in the pharmaceutical field.
[0073] A unit measurement of its formulation includes 1 mg-700 mg of compound of formula I, and preferably, the unit measurement of the formulation includes 25 mg-300 mg of compound of formula I.
[0074] The compounds and pharmaceutical compositions of the present invention can be used clinically in mammals, including humans and animals, and can be administered through oral, nasal, dermal, pulmonary, or gastrointestinal routes. The most preferred option is oral administration. The most preferred daily dose is 50-1400 mg/kg body weight, taken in one dose, or 25-700 mg/kg body weight in divided doses. Regardless of the method of administration, the optimal dosage for an individual should be determined based on the specific treatment. Usually, it starts from a small dose and gradually increases until the most suitable dose is found.
[0075] Another aspect of the present invention provides a method for increasing cerebral blood flow, comprising selected from one or more of a compound of Formula I, a pharmaceutically acceptable salt, a enantiomer, a diastereomer and a racemate, and optionally, one or more pharmaceutically acceptable carriers, excipients, adjuvants, accessories and/or diluents.
[0076] The compounds and compositions of the present invention were used for the treatment and prevention of neurodegenerative diseases and stroke related to cerebral blood flow, including but not limited to Alzheimer's disease, vascular dementia, and stroke.
[0077] The present invention will be further explained in conjunction with specific examples. It should be understood that these examples were only used to illustrate the present invention and not to limit the scope of the present invention. The experimental methods without specific conditions specified in the following examples were usually carried out under conventional conditions or conditions recommended by the manufacturer. Unless otherwise specified, percentages and portions are calculated by weight.
Example 1 (E)-3-(3-(o-methylphenyl)acryloyl)oxazolidin-2-one
##STR00005##
[0078] To a solution of compound (E)-3-(o-methylphenyl)acrylic acid 1a (400.0 mg, 2.47 mmol) and triethylamine (685.6 L, 4.93 mmol) in ultra dry dichloromethane was added pivaloyl chloride (364.5 L, 2.96 mmol) at 78 C. and stirred at room temperature for 1 hour under argon protection. Then oxazolidin-2-one (214.8 mg, 2.47 mmol) and lithium chloride (104.5 mg, 2.47 mmol) was added at 78 C. and stirred at room temperature for 12 hours. After TLC monitored the completion of the reaction, it was quenched with water and extracted with dichloromethane. The organic layers were combined and washed with saturated sodium chloride solution. Then the organic layer was dried with anhydrous sodium sulfate and concentrated, the crude product was subjected to column chromatography to obtain the target product (E)-3-(3-(o-methylphenyl)acryloyl)oxazolidin-2-one (490 mg, white solid), yield 85.9%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.96 (d, J=15.7 Hz, 1H), 7.73 (d, J=15.7 Hz, 1H), 7.61 (d, J=8.7 Hz, 1H), 7.38-7.31 (m, 1H), 7.30 (d, J=3.9 Hz, 2H), 4.47-4.37 (m, 2H), 4.06-3.97 (m, 2H), 2.41 (s, 3H). LRMS (ESI): 232.09 [M+H]+.
Example 2 (E)-3-(3-(m-Methylphenyl)Acryloyl)Oxazolidin-2-One
[0079] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(m-methylphenyl)acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(m-methylphenyl)acryloyl)oxazolidin-2-one (yield 82.1%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=16.0 Hz, 1H), 7.72 (d, J=16.0 Hz, 1H), 7.51-7.44 (m, 2H), 7.36 (dt, J=10.2, 5.1 Hz, 1H), 7.28 (d, J=7.8 Hz, 1H), 4.42 (td, J=8.1, 2.4 Hz, 2H), 4.00 (td, J=8.1, 2.6 Hz, 2H), 2.34 (s, 3H). LRMS (ESI): 232.09 [M+H]+.
Example 3 (E)-3-(3-(p-methylphenyl)acryloyl)oxazolidin-2-one
[0080] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(p-methylphenyl)acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(p-methylphenyl)acryloyl)oxazolidin-2-one (yield 85.2%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.77 (d, J=15.8 Hz, 1H), 7.70 (d, J=15.9 Hz, 1H), 7.55 (d, J=8.2 Hz, 2H), 7.26 (d, J=7.9 Hz, 2H), 4.39 (dd, J=8.6, 7.4 Hz, 2H), 3.97 (dd, J=8.6, 7.4 Hz, 2H), 2.32 (s, 3H). LRMS (ESI): 232.09 [M+H]+.
Example 4 (E)-3-(3-(2-methoxyphenyl)acryloyl)oxazolidin-2-one
[0081] Replace (E)-3-(2-methoxyphenyl)acrylic acid with (E)-3-(2-methoxyphenyl)acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(2-methoxyphenyl)acryloyl)oxazolidin-2-one (yield 87.2%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.97 (d, J=16.0 Hz, 1H), 7.88 (d, J=15.9 Hz, 1H), 7.61 (dd, J=7.7, 1.6 Hz, 1H), 7.45 (ddd, J=8.5, 7.3, 1.6 Hz, 1H), 7.12 (d, J=8.4 Hz, 1H), 7.03 (t, J=7.5 Hz, 1H), 4.41 (t, J=8.0 Hz, 2H), 3.99 (dd, J=8.5, 7.4 Hz, 2H), 3.88 (s, 3H). LRMS (ESI): 248.08 [M+H]+.
Example 5 (E)-3-(3-(3-methoxyphenyl)acryloyl)oxazolidin-2-one
[0082] Replace (E)-3-(o-methoxyphenyl)acrylic acid with (E)-3-(3-methoxyphenyl)acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(3-methoxyphenyl)acryloyl)oxazolidin-2-one (yield 87.6%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=15.8 Hz, 1H), 7.73 (d, J=15.8 Hz, 1H), 7.39 (t, J=7.9 Hz, 1H), 7.31-7.24 (m, 1H), 7.21 (t, J=2.0 Hz, 1H), 7.08-7.02 (m, 1H), 4.42 (dd, J=8.5, 7.4 Hz, 2H), 4.00 (dd, J=8.6, 7.3 Hz, 2H), 3.80 (s, 3H). LRMS (ESI): 248.08 [M+H]+.
Example 6 (E)-3-(3-(4-methoxyphenyl)acryloyl)oxazolidin-2-one
[0083] Replace (E)-3-(o-methoxyphenyl)acrylic acid with (E)-3-(4-methoxyphenyl)acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-methoxyphenyl)acryloyl)oxazolidin-2-one (yield 82.7%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.77-7.66 (m, 2H), 7.64 (d, J=8.7 Hz, 2H), 7.03 (d, J=8.8 Hz, 2H), 4.41 (dd, J=8.5, 7.4 Hz, 2H), 3.99 (dd, J=8.5, 7.4 Hz, 2H), 3.81 (s, 3H). LRMS (ESI): 248.08 [M+H]+.
Example 7 (E)-3-(3-(2-(trifluoromethylphenyl)acryloyl)oxazolidin-2-one
[0084] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(2-(trifluoromethylphenyl)acryloyl) oxazolidin-2-one (yield 81.5%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.98-7.78 (m, 5H), 7.68 (t, J=7.6 Hz, 1H), 4.43 (dd, J=8.5, 7.4 Hz, 2H), 4.02 (dd, J=8.5, 7.4 Hz, 2H). LRMS (ESI): 286.06 [M+H]+.
Example 8 (E)-3-(3-(3-(trifluoromethylphenyl)acryloyl)oxazolidin-2-one
[0085] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(3-trifluoromethylphenyl) acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(3-(trifluoromethylphenyl)acryloyl) oxazolidin-2-one (yield 80.3%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.05-7.97 (m, 2H), 7.94-7.83 (m, 2H), 7.82 (d, J=7.1 Hz, 1H), 7.71 (t, J=7.8 Hz, 1H), 4.43 (dd, J=8.5, 7.4 Hz, 2H), 4.02 (dd, J=8.5, 7.4 Hz, 2H). LRMS (ESI): 286.06 [M+H]+.
Example 9 (E)-3-(3-(4-(trifluoromethylphenyl)acryloyl)oxazolidin-2-one
[0086] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(4-trifluoromethylphenyl) acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-(trifluoromethylphenyl)acryloyl) oxazolidin-2-one (yield 85.6%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.95-7.87 (m, 3H), 7.85-7.79 (m, 3H), 4.43 (dd, J=8.5, 7.4 Hz, 2H), 4.01 (dd, J=8.6, 7.4 Hz, 2H). LRMS (ESI): 286.06 [M+H]+.
Example 10 (E)-3-(3-(2-fluorophenyl)acryloyl)oxazolidin-2-one
[0087] Replace (E)-3-(ortho methylphenyl)acrylic acid with (E)-3-(2-fluorophenyl)acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(2-fluorophenyl)acryloyl)oxazolidin-2-one (yield 92.1%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.93 (d, J=16.0 Hz, 1H), 7.77 (d, J=16.0 Hz, 1H), 7.79-7.72 (m, 1H), 7.58-7.47 (m, 1H), 7.42-7.26 (m, 2H), 4.50-4.37 (m, 2H), 4.01 (m, 2H). LRMS (ESI): 236.06 [M+H]+.
Example 11 (E)-3-(3-(4-fluorophenyl)acryloyl)oxazolidin-2-one
[0088] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(4-fluorophenyl)acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-fluorophenyl)acryloyl)oxazolidin-2-one (yield 89.0%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.77 (s, 2H), 7.77-7.73 (m, 2H), 7.37-7.25 (m, 2H), 4.42 (dd, J=8.6, 7.3 Hz, 2H), 4.00 (dd, J=8.5, 7.4 Hz, 2H). LRMS (ESI): 236.06 [M+H]+.
Example 12 (E)-3-(3-(4-chlorophenyl)acryloyl)oxazolidin-2-one
[0089] Replace (E)-3-(4-chlorophenyl)acrylic acid with (E)-3-(4-chlorophenyl)acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-chlorophenyl)acryloyl)oxazolidin-2-one (yield 91.1%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.82 (d, J=15.9 Hz, 1H), 7.75 (d, J=15.9 Hz, 1H), 7.73-7.68 (m, 2H), 7.53 (dd, J=8.4, 1.2 Hz, 2H), 4.42 (t, J=8.0 Hz, 2H), 4.00 (t, J=8.0 Hz, 2H). LRMS (ESI): 252.03 [M+H]+.
Example 13 (E)-3-(3-(2-bromophenyl)acryloyl)oxazolidin-2-one
[0090] Replace (E)-3-(ortho methylphenyl)acrylic acid with (E)-3-(2-bromophenyl)acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(2-bromophenyl)acryloyl)oxazolidin-2-one (yield 93.4%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.96 (dd, J=15.9, 1.7 Hz, 1H), 7.84-7.73 (m, 3H), 7.50 (td, J=7.5, 1.4 Hz, 1H), 7.39 (td, J=7.7, 1.8 Hz, 1H), 4.43 (td, J=7.9, 1.7 Hz, 2H), 4.01 (ddd, J=8.7, 7.2, 1.7 Hz, 2H). LRMS (ESI): 295.98, 297.98 [M+H]+.
Example 14 (E)-3-(3-(4-bromophenyl)acryloyl)oxazolidin-2-one
[0091] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(4-bromophenyl)acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-bromophenyl)acryloyl)oxazolidin-2-one (yield 91.1%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.83 (d, J=15.9 Hz, 1H), 7.73 (d, J=15.9 Hz, 1H), 7.67 (d, J=8.7 Hz, 2H), 7.63 (d, J=8.7 Hz, 2H), 4.42 (dd, J=8.6, 7.4 Hz, 2H), 4.00 (dd, J=8.5, 7.4 Hz, 2H). LRMS (ESI): 295.98, 297.98 [M+H]+.
Example 15 (E)-3-(3-(2-phenoxyphenyl)acryloyl)oxazolidin-2-one
[0092] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-phenoxyphenyl)acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(2-phenoxyphenyl)acryloyl)oxazolidin-2-one (yield 89.3%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.99-7.88 (m, 2H), 7.83-7.76 (m, 1H), 7.50-7.44 (m, 1H), 7.41 (tq, J=7.4, 1.2 Hz, 2H), 7.27 (td, J=7.6, 1.5 Hz, 1H), 7.17 (tt, J=7.4, 1.2 Hz, 1H), 7.05-6.98 (m, 2H), 6.96 (dt, J=8.2, 1.3 Hz, 1H), 4.40 (td, J=8.0, 1.4 Hz, 2H), 4.01-3.91 (m, 2H). LRMS (ESI): 310.10 [M+H]+.
Example 16 (E)-3-(3-(3-phenoxyphenyl)acryloyl)oxazolidin-2-one
[0093] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(3-phenoxyphenyl)acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(3-phenoxyphenyl)acryloyl)oxazolidin-2-one (yield 82.7%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.80-7.70 (m, 2H), 7.49-7.39 (m, 4H), 7.31 (dd, J=2.9, 1.4 Hz, 1H), 7.22-7.15 (m, 1H), 7.10-7.00 (m, 3H), 4.45-4.36 (m, 2H), 4.03-3.94 (m, 2H). LRMS (ESI): 310.10 [M+H]+.
Example 17 (E)-3-(3-(4-phenoxyphenyl)acryloyl)oxazolidin-2-one
[0094] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(4-phenoxyphenyl)acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-phenoxyphenyl)acryloyl)oxazolidin-2-one (yield 88.10%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=15.1 Hz, 1H), 7.61-7.52 (m, 1H), 7.54-7.45 (m, 2H), 7.39 (t, J=7.5 Hz, 2H), 7.19-7.10 (m, 1H), 7.06 (ddd, J=7.8, 5.7, 1.9 Hz, 4H), 4.40 (t, J=6.3 Hz, 2H), 4.05 (t, J=6.4 Hz, 2H). LRMS (ESI): 310.10 [M+H]+.
Example 18 (E)-3-(3-([1,1-biphenyl]-2-yl)acryloyl)oxazolidin-2-one
[0095] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-([1,1-biphenyl]-2-yl) acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-([1,1-biphenyl]-2-yl)acryloyl) oxazolidin-2-one (yield 86.7%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.90-7.78 (m, 2H), 7.64 (dd, J=15.8, 1.4 Hz, 1H), 7.60-7.39 (m, 6H), 7.33 (dt, J=7.8, 1.5 Hz, 2H), 4.47-4.36 (m, 2H), 3.95 (m, 2H). LRMS (ESI): 294.11 [M+H]+.
Example 19 (E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)oxazolidin-2-one
[0096] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-([1,1-biphenyl]-3-yl) acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl) oxazolidin-2-one (yield 88.3%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.94 (s, 1H), 7.88 (d, J=5.9 Hz, 2H), 7.78-7.68 (m, 4H), 7.57 (t, J=7.7 Hz, 1H), 7.51 (t, J=7.6 Hz, 2H), 7.42 (t, J=7.3 Hz, 1H), 4.43 (t, J=8.0 Hz, 2H), 4.02 (t, J=7.9 Hz, 2H). LRMS (ESI): 294.11 [M+H]+.
Example 20 (E)-3-(3-(4-fluoro-2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one
[0097] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(4-fluoro-2-trifluoromethylphenyl)acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-fluoro-2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one (yield 81.0%). .sup.1H NMR (400 MHz, Chloroform-d) 8.15 (dq, J=15.6, 2.3 Hz, 1H), 7.91-7.78 (m, 2H), 7.42 (dd, J=8.8, 2.7 Hz, 1H), 7.35-7.22 (m, 1H), 4.49 (t, J=8.0 Hz, 2H), 4.16 (t, J=8.0 Hz, 2H). LRMS (ESI): 304.05 [M+H]+.
Example 21 (E)-3-(3-(naphthalen-1-yl)acryloyl)oxazolidin-2-one
[0098] Replace (E)-3-(ortho methylphenyl)acrylic acid with (E)-3-(naphthalen-1-yl) acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(naphthalen-1-yl)acryloyl)oxazolidin-2-one (yield 87.1%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.52 (d, J=15.6 Hz, 1H), 8.25 (d, J=8.3 Hz, 1H), 8.09-8.00 (m, 2H), 7.95-7.86 (m, 2H), 7.69-7.58 (m, 3H), 4.45 (dd, J=8.6, 7.3 Hz, 2H), 4.05 (dd, J=8.6, 7.3 Hz, 2H). LRMS (ESI): 268.09 [M+H]+.
Example 22 (E)-3-(3-(benzo [d][1,3]dioxolan-5-yl)acryloyl)oxazolidin-2-one
[0099] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(benzo [d][1,3]dioxolane-5-yl)acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(benzo [d][1,3]dioxolane-5-yl)acryloyl)oxazolin-2-one (yield 89.2%). .sup.1H NMR (400 MHz, Chloroform-d) 7.79 (d, J=15.7 Hz, 1H), 7.73 (d, J=15.6 Hz, 1H), 7.15 (d, J=1.7 Hz, 1H), 7.10 (dd, J=8.0, 1.8 Hz, 1H), 6.82 (d, J=8.0 Hz, 1H), 6.02 (s, 2H), 4.45 (dd, J=8.6, 7.5 Hz, 2H), 4.13 (dd, J=8.5, 7.4 Hz, 2H); LRMS (ESI): 262.06 [M+H]+.
Example 23 (E)-3-(3-(thiphen-2-yl)acryloyl)oxazolidin-2-one
[0100] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(thiphen-2-yl)acrylic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(thiphen-2-yl)acryloyl)oxazolidin-2-one (yield 87.4%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.03 (dd, J=2.8, 1.2 Hz, 1H), 7.77 (d, J=15.8 Hz, 1H), 7.66 (ddd, J=5.0, 2.9, 0.7 Hz, 1H), 7.61 (d, J=15.7 Hz, 1H), 7.42 (dd, J=5.1, 1.2 Hz, 1H), 4.41 (dd, J=8.5, 7.4 Hz, 2H), 3.99 (dd, J=8.5, 7.4 Hz, 2H). LRMS (ESI): 224.03 [M+H]+.
Example 24 (E)-3-(3-cyclohexylcacryloyl)oxazolidin-2-one
[0101] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-cyclohexanoic acid. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-cyclohexanoyl)oxazolidin-2-one (yield 85.1%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.12 (dd, J=15.6, 1.3 Hz, 1H), 6.95 (dd, J=15.6, 6.6 Hz, 1H), 4.37 (dd, J=8.5, 7.5 Hz, 2H), 3.92 (dd, J=8.6, 7.4 Hz, 2H), 2.21 (qd, J=8.0, 7.3, 4.5 Hz, 1H), 1.77-1.68 (m, 4H), 1.63 (d, J=12.5 Hz, 1H), 1.36-1.23 (m, 2H), 1.14 (pd, J=13.3, 12.7, 3.7 Hz, 3H).
[0102] LRMS (ESI): 224.12 [M+H]+.
Example 26 (E)-3-(3-(2-trifluoromethylphenyl)acryloyl)-4-phenyloxazolidin-2-one
[0103] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolidin-2-one with 4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(2-trifluoromethylphenyl)acryloyl)-4-phenyloxazolidin-2-one (yield 89.9%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.95 (d, J=7.8 Hz, 1H), 7.91-7.77 (m, 4H), 7.68 (t, J=7.7 Hz, 1H), 7.46-7.33 (m, 5H), 5.59 (dd, J=8.6, 4.1 Hz, 1H), 4.82 (t, J=8.7 Hz, 1H), 4.24 (dd, J=8.7, 4.1 Hz, 1H). LRMS (ESI): 362.09 [M+H]+.
Example 27 (S, E)-3-(3-(2-trifluoromethylphenyl)acryloyl)-4-phenyloxazolidin-2-one
[0104] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-(2-trifluoromethylphenyl)acryloyl)-4-phenyloxazolidin-2-one (yield 90.9%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.95 (d, J=7.8 Hz, 1H), 7.91-7.77 (m, 4H), 7.68 (t, J=7.7 Hz, 1H), 7.46-7.33 (m, 5H), 5.59 (dd, J=8.6, 4.1 Hz, 1H), 4.82 (t, J=8.7 Hz, 1H), 4.24 (dd, J=8.7, 4.1 Hz, 1H). LRMS (ESI): 362.09 [M+H]+.
Example 28 (R, E)-3-(3-(2-trifluoromethylphenyl)acryloyl)-4-phenyloxazolidin-2-one
[0105] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolidin-2-one with (R)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (R, E)-3-(3-(2-trifluoromethylphenyl)acryloyl)-4-phenyloxazolidin-2-one (yield 90.4%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.95 (d, J=7.8 Hz, 1H), 7.91-7.77 (m, 4H), 7.68 (t, J=7.7 Hz, 1H), 7.46-7.33 (m, 5H), 5.59 (dd, J=8.6, 4.1 Hz, 1H), 4.82 (t, J=8.7 Hz, 1H), 4.24 (dd, J=8.7, 4.1 Hz, 1H). LRMS (ESI): 362.09 [M+H]+.
Example 29 (S, E)-4-phenyl-3-(3-(3-(trifluoromethoxy)phenyl)acryloyl) oxazolidin-2-one
[0106] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-(3-(trifluoromethoxy)phenyl) acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-phenyl-3-(3-(trifluoromethoxy)phenyl)acryloyl) oxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 7.94 (d, J=15.7 Hz, 1H), 7.72 (d, J=15.7 Hz, 1H), 7.52 (dt, J=7.8, 1.3 Hz, 1H), 7.45-7.32 (m, 7H), 7.25 (ddd, J=8.2, 2.7, 1.5 Hz, 1H), 5.56 (dd, J=8.7, 3.9 Hz, 1H), 4.75 (t, J=8.8 Hz, 1H), 4.33 (dd, J=8.9, 3.9 Hz, 1H); LRMS (ESI): 378.09 [M+H]+.
Example 30 (S, E)-4-phenyl-3-(3-(2-(trifluoromethoxy)phenyl)acryloyl) oxazolidin-2-one
[0107] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-(2-(trifluoromethoxy)phenyl) acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-phenyl-3-(3-(2-(trifluoromethoxy)phenyl)acryloyl) oxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 8.05 (d, J=15.8 Hz, 1H), 7.97 (d, J=15.9 Hz, 1H), 7.84-7.75 (m, 1H), 7.47-7.25 (m, 8H), 5.56 (dd, J=8.8, 3.9 Hz, 1H), 4.76 (t, J=8.8 Hz, 1H), 4.34 (dd, J=8.9, 3.9 Hz, 1H); LRMS (ESI): 378.09 [M+H]+.
Example 31 (S, E)-4-phenyl-3-(3-(4-(trifluoromethoxy)phenyl)acryloyl) oxazolidin-2-one
[0108] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-(4-(trifluoromethoxy)phenyl) acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-phenyl-3-(3-(4-(trifluoromethoxy)phenyl)acryloyl) oxazolidin-2-one. .sup.1H NMR (400 MHz, Methylene Chloride-d.sub.2) 7.90 (d, J=15.8 Hz, 1H), 7.73 (d, J=15.7 Hz, 1H), 7.68-7.63 (m, 2H), 7.44-7.32 (m, 5H), 7.28-7.22 (m, 2H), 5.53 (dd, J=8.7, 4.1 Hz, 1H), 4.74 (t, J=8.8 Hz, 1H), 4.29 (dd, J=8.9, 4.1 Hz, 1H); LRMS (ESI): 378.09 [M+H]+.
Example 32 (S, E)-3-(3-(2-phenoxyphenyl)acryloyl)-4-phenyloxazolidin-2-one
[0109] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-phenoxyphenyl)acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-(2-phenoxyphenyl)acryloyl)-4-phenyloxazolidin-2-one (yield 90.1%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.98 (d, J=15.9 Hz, 1H), 7.84 (d, J=16.0 Hz, 1H), 7.80 (dd, J=7.9, 1.7 Hz, 1H), 7.47 (ddd, J=8.3, 7.3, 1.7 Hz, 1H), 7.43-7.36 (m, 4H), 7.35-7.25 (m, 4H), 7.18-7.13 (m, 1H), 7.03-6.97 (m, 2H), 6.94 (dd, J=8.2, 1.1 Hz, 1H), 5.55 (dd, J=8.6, 3.9 Hz, 1H), 4.79 (t, J=8.7 Hz, 1H), 4.20 (dd, J=8.7, 3.9 Hz, 1H). LRMS (ESI): 386.13 [M+H]+.
Example 33 (R, E)-3-(3-(2-phenoxyphenyl)acryloyl)-4-phenyloxazolidin-2-one
[0110] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-phenoxyphenyl)acrylic acid, and replace oxazolidin-2-one with (R)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (R, E)-3-(3-(2-phenoxyphenyl)acryloyl)-4-phenyloxazolidin-2-one (yield 90.5%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.98 (d, J=15.9 Hz, 1H), 7.84 (d, J=16.0 Hz, 1H), 7.80 (dd, J=7.9, 1.7 Hz, 1H), 7.47 (ddd, J=8.3, 7.3, 1.7 Hz, 1H), 7.43-7.36 (m, 4H), 7.35-7.25 (m, 4H), 7.18-7.13 (m, 1H), 7.03-6.97 (m, 2H), 6.94 (dd, J=8.2, 1.1 Hz, 1H), 5.55 (dd, J=8.6, 3.9 Hz, 1H), 4.79 (t, J=8.7 Hz, 1H), 4.20 (dd, J=8.7, 3.9 Hz, 1H). LRMS (ESI): 386.13 [M+H]+.
Example 34 (E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one
[0111] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-([1,1-biphenyl]-3-yl) acrylic acid, replace oxazolidin-2-one with 4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one (yield 86.9%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.96-7.89 (m, 2H), 7.81-7.67 (m, 5H), 7.56 (t, J=7.7 Hz, 1H), 7.50 (dd, J=8.2, 6.9 Hz, 2H), 7.44-7.32 (m, 6H), 5.61 (dd, J=8.6, 3.9 Hz, 1H), 4.82 (t, J=8.7 Hz, 1H), 4.23 (dd, J=8.6, 3.9 Hz, 1H). LRMS (ESI, m/z): 370.14 [M+H]+
Example 35 (S, E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one
[0112] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-([1,1-biphenyl]-3-yl) acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one (yield 89.6%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.00-7.88 (m, 2H), 7.81-7.66 (m, 5H), 7.56 (t, J=7.7 Hz, 1H), 7.53-7.47 (m, 2H), 7.45-7.33 (m, 6H), 5.61 (dd, J=8.6, 3.9 Hz, 1H), 4.87-4.78 (m, 1H), 4.27-4.20 (m, 1H). LRMS (ESI): 370.14 [M+H]+.
Example 36 (R, E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one
[0113] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-([1,1-biphenyl]-3-yl) acrylic acid, and replace oxazolidin-2-one with (R)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (R, E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one (yield 88.9%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.00-7.88 (m, 2H), 7.81-7.66 (m, 5H), 7.56 (t, J=7.7 Hz, 1H), 7.53-7.47 (m, 2H), 7.45-7.33 (m, 6H), 5.61 (dd, J=8.6, 3.9 Hz, 1H), 4.87-4.78 (m, 1H), 4.27-4.20 (m, 1H). LRMS (ESI): 370.14 [M+H]+.
Example 37 (S, E)-3-(3-(4-fluorine-[1,1-biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one
[0114] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(4-fluorine-[1,1-biphenyl]-3-yl)acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the 20 same as in Example 1 to obtain (S, E)-3-(3-(4-fluorine-[1,1-biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one (yield 78.1%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.94-7.87 (m, 2H), 7.80-7.70 (m, 4H), 7.68 (dt, J=7.9, 1.3 Hz, 1H), 7.55 (t, J=7.7 Hz, 1H), 7.43-7.39 (m, 1H), 7.39-7.36 (m, 2H), 7.36-7.28 (m, 4H), 5.61 (dd, J=8.6, 3.9 Hz, 1H), 4.82 (t, J=8.7 Hz, 1H), 4.23 (dd, J=8.6, 3.9 Hz, 1H). LRMS (ESI): 409.9 [M+Na]+.
Example 38 (S, E)-4-phenyl-3-(3-(3-(pyridin-3-yl)phenyl)acryloyl)oxazolidin-2-one
[0115] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(3-(pyridin-3-yl)phenyl) acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-phenyl-3-(3-(pyridin-3-yl)phenyl)acryloyl)oxazolidin-2-one (yield 67.1%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.95 (d, J=2.4 Hz, 1H), 8.61 (dd, J=4.8, 1.6 Hz, 1H), 8.13 (dt, J=8.0, 2.0 Hz, 1H), 8.01 (t, J=1.7 Hz, 1H), 7.93 (d, J=15.9 Hz, 1H), 7.85-7.72 (m, 3H), 7.61 (t, J=7.8 Hz, 1H), 7.52 (dd, J=8.0, 4.8 Hz, 1H), 7.45-7.31 (m, 5H), 5.61 (dd, J=8.6, 3.9 Hz, 1H), 4.82 (t, J=8.6 Hz, 1H), 4.23 (dd, J=8.6, 3.9 Hz, 1H). LRMS (ESI): 393.01 [M+Na].sup.+.
Example 39 (S, E)-4-phenyl-3-(3-(3-(pyridin-4-yl)phenyl)acryloyl)oxazolidin-2-one
[0116] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(3-(pyridin-4-yl)phenyl) acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-phenyl-3-(3-(pyridin-4-yl)phenyl)acryloyl)oxazolidin-2-one (yield 65.5%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.70-8.65 (m, 2H), 8.07 (s, 1H), 7.97-7.90 (m, 1H), 7.89 (d, J=7.4 Hz, 1H), 7.82-7.73 (m, 4H), 7.62 (t, J=7.6 Hz, 1H), 7.45-7.31 (m, 5H), 5.61 (dd, J=8.6, 3.9 Hz, 1H), 4.82 (t, J=8.6 Hz, 1H), 4.23 (dd, J=8.6, 3.9 Hz, 1H).
[0117] LRMS (ESI): 392.92 [M+Na]+.
Example 40 (S, E)-4-phenyl-3-(3-(3-(thiphen-2-yl)phenyl)acryloyl)oxazolidin-2-one
[0118] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(3-(thiphen-2-yl)phenyl) acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-phenyl-3-(3-(thiphen-2-yl)phenyl)acryloyl)oxazolidin-2-one (yield 87.8%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=15.0 Hz, 1H), 7.78-7.66 (m, 2H), 7.62 (q, J=1.7 Hz, 1H), 7.55 (d, J=15.2 Hz, 1H), 7.55-7.43 (m, 2H), 7.45-7.35 (m, 3H), 7.36-7.26 (m, 2H), 7.29-7.19 (m, 1H), 7.13 (t, J=7.5 Hz, 1H), 5.29 (t, J=7.0 Hz, 1H), 5.08 (dd, J=11.5, 7.0 Hz, 1H), 4.80 (dd, J=11.5, 7.0 Hz, 1H). LRMS (ESI): 376.09 [M+H]+.
Example 41 (S, E)-4-phenyl-3-(3-(5-phenylthiophen-2-yl)acryloyl)oxazolidin-2-one
[0119] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(5-phenylthiphen-2-yl) acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-phenyl-3-(3-(5-phenylthiphen-2-yl)acryloyl)oxazolidin-2-one (yield 91.3%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.89 (d, J=7.6 Hz, 1H), 7.87-7.77 (m, 3H), 7.71 (d, J=7.4 Hz, 1H), 7.55 (d, J=15.1 Hz, 1H), 7.52-7.44 (m, 3H), 7.47-7.38 (m, 2H), 7.31 (t, J=7.3 Hz, 2H), 7.29-7.19 (m, 1H), 5.29 (t, J=7.0 Hz, 1H), 5.07 (dd, J=11.5, 7.0 Hz, 1H), 4.81 (dd, J=11.4, 6.9 Hz, 1H). LRMS (ESI): 376.09 [M+H]+.
Example 42 (S, E)-4-phenyl-3-(3-(4-phenylthiophen-2-yl)acryloyl)oxazolidin-2-one
[0120] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(4-phenylthiphen-2-yl) acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-phenyl-3-(3-(4-phenylthiphen-2-yl)acryloyl)oxazolidin-2-one (yield 92.1%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.86-7.77 (m, 3H), 7.63-7.53 (m, 3H), 7.42 (dtdd, J=9.3, 7.1, 4.5, 3.0 Hz, 5H), 7.31 (t, J=7.3 Hz, 2H), 7.29-7.19 (m, 1H), 5.31 (t, J=6.9 Hz, 1H), 5.08 (dd, J=11.4, 6.9 Hz, 1H), 4.81 (dd, J=11.5, 7.0 Hz, 1H).
[0121] LRMS (ESI): 376.09 [M+H]+.
Example 43 (S, E)-3-(3-(4-fluoro-2-(trifluoromethyl)phenyl)acryloyl)-4-phenyloxazolidin-2-one
[0122] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-4-fluoro-2-(trifluoromethyl)phenyl)acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-(4-fluoro-2-(trifluoromethyl)phenyl)acryloyl)-4-phenyloxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 8.08 (d, J=15.4 Hz, 1H), 7.95-7.80 (m, 2H), 7.39 (dt, J=15.8, 7.4 Hz, 6H), 7.32-7.22 (m, 1H), 5.55 (dd, J=8.7, 3.9 Hz, 1H), 4.76 (t, J=8.8 Hz, 1H), 4.35 (dd, J=8.9, 3.9 Hz, 1H); LRMS (ESI): 380.24 [M+H].
Example 44 (S, E)-3-(3-(benzo [d][1,3]dioxolan-5-yl)acryloyl)-4-phenyloxazolidin-2-one
[0123] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(benzo [d][1,3]dioxolan-5-yl)acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-(benzo [d][1,3]dioxolan-5-yl)acryloyl)-4-phenyloxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 7.84-7.64 (m, 2H), 7.44-7.29 (m, 5H), 7.13 (d, J=1.7 Hz, 1H), 7.05 (dd, J=8.1, 1.7 Hz, 1H), 6.80 (d, J=8.0 Hz, 1H), 6.01 (s, 2H), 5.55 (dd, J=8.7, 3.9 Hz, 1H), 4.73 (t, J=8.8 Hz, 1H), 4.31 (dd, J=8.8, 3.8 Hz, 1H); LRMS (ESI): 338.10 [M+H]+.
Example 45 (S, E)-3-(3-(2-chloroquinolin-4-yl)acryloyl)-4-phenyloxazolidin-2-one
[0124] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-chloroquinolin-4-yl) acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-(2-chloroquinolin-4-yl)acryloyl)-4-phenyloxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 8.38 (dd, J=15.6, 0.8 Hz, 1H), 8.13-8.05 (m, 3H), 7.77 (ddd, J=8.4, 6.9, 1.4 Hz, 1H), 7.64 (s, 1H), 7.63-7.58 (m, 1H), 7.40 (m, 5H), 5.59 (dd, J=8.8, 4.0 Hz, 1H), 4.81 (t, J=8.8 Hz, 1H), 4.43-4.35 (m, 1H); LRMS (ESI): 379.08 [M+H].sup.+.
Example 46 (S, E)-3-(3-(benzofuran-2-yl)acryloyl)-4-phenyloxazolidin-2-one
[0125] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(benzofuran-2-yl)acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-(benzofuran-2-yl)acryloyl)-4-phenyloxazolidin-2-one. .sup.1H NMR (400 MHz, Methylene Chloride-d.sub.2) 7.95 (d, J=15.4 Hz, 1H), 7.67-7.58 (m, 2H), 7.55 (dt, J=8.4, 1.0 Hz, 1H), 7.45-7.32 (m, 6H), 7.30-7.22 (m, 1H), 7.03 (d, J=4.6 Hz, 1H), 5.54 (dd, J=8.8, 4.1 Hz, 1H), 4.75 (t, J=8.8 Hz, 1H), 4.29 (dd, J=8.9, 4.1 Hz, 1H); LRMS (ESI): 334.10 [M+H]+.
Example 47 (S, E)-3-(3-(benzofuran-7-yl)acryloyl)-4-phenyloxazolidin-2-one
[0126] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(benzofuran-7-yl)acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-(benzofuran-7-yl)acryloyl)-4-phenyloxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 7.97 (d, J=15.7 Hz, 1H), 7.92 (d, J=15.7 Hz, 1H), 7.86 (d, J=1.7 Hz, 1H), 7.67 (d, J=2.2 Hz, 1H), 7.60 (dd, J=8.6, 1.8 Hz, 1H), 7.52 (d, J=8.6 Hz, 1H), 7.46-7.35 (m, 5H), 6.82 (dd, J=2.3, 0.9 Hz, 1H), 5.60 (dd, J=8.7, 3.9 Hz, 1H), 4.78 (t, J=8.8 Hz, 1H), 4.35 (dd, J=8.8, 3.9 Hz, 1H); LRMS (ESI): 334.10 [M+H]+.
Example 48 (S, E)-3-(3-(naphthalen-1-yl)acryloyl)-4-phenyloxazolidin-2-one
[0127] Replace (E)-3-(ortho methylphenyl)acrylic acid with (E)-3-(naphthalen-1-yl) acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-(naphthalen-1-yl)acryloyl)-4-phenyloxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 8.68 (d, J=15.5 Hz, 1H), 8.20 (d, J=8.1 Hz, 1H), 8.05 (dt, J=15.5, 0.9 Hz, 1H), 7.97-7.91 (m, 2H), 7.91-7.86 (m, 1H), 7.60-7.50 (m, 3H), 7.48-7.35 (m, 5H), 5.63 (dd, J=8.7, 3.9 Hz, 1H), 4.80 (ddt, J=9.7, 8.8, 1.0 Hz, 1H), 4.41-4.34 (m, 1H); LRMS (ESI): 344.12 [M+H].sup.+.
Example 49 (S, E)-3-(3-(benzo [b]thiophen-2-yl)acryloyl)-4-phenyloxazolidin-2-one
[0128] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(benzo [b]thiophen-2-yl) acrylic acid, and replace oxazolidin-2-one with (S)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-(benzo [b]thiophen-2-yl)acryloyl)-4-phenyloxazolidin-2-one. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.05-7.95 (m, 2H), 7.93-7.82 (m, 2H), 7.69 (d, J=15.5 Hz, 1H), 7.39 (dp, J=21.3, 8.2, 7.0 Hz, 7H), 5.59 (dd, J=8.7, 3.9 Hz, 1H), 4.81 (t, J=8.7 Hz, 1H), 4.22 (dd, J=8.7, 3.9 Hz, 1H); LRMS (ESI): 350.08 [M+H]+.
Example 50 (E)-4-(4-fluorophenyl)-3-(3-(2-(trifluoromethylphenyl)acryloyl) oxazolidin-2-one
[0129] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolin-2-one with 4-(4-fluorophenyl)oxazolin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-4-(4-fluorophenyl)-3-(3-(2-(trifluoromethylphenyl)acryloyl) oxazolin-2-one. LRMS (ESI): 380.08 [M+H]+.
Example 51 (S, E)-4-(4-fluorophenyl)-3-(3-(2-(trifluoromethylphenyl) acryloyl)oxazolidin-2-one
[0130] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolidin-2-one with (S)-4-(4-fluorophenyl)oxazolidin-2-one.
[0131] The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-(4-fluorophenyl)-3-(3-(2-(trifluoromethylphenyl) acryloyl)oxazolidin-2-one. LRMS (ESI): 380.08 [M+H]+.
Example 52 (E)-4-(4-fluorophenyl)-3-(3-(2-(trifluoromethoxyphenyl) acryloyl)oxazolidin-2-one
[0132] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethoxyphenyl) acrylic acid, and replace oxazolidin-2-one with 4-(4-fluorophenyl)oxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-4-(4-fluorophenyl)-3-(3-(2-(trifluoromethoxyphenyl)acryloyl) oxazolidin-2-one. LRMS (ESI): 396.08 [M+H].sup.+.
Example 53 (S, E)-4-(4-fluorophenyl)-3-(3-(2-(trifluoromethoxyphenyl) acryloyl)oxazolidin-2-one
[0133] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethoxyphenyl) acrylic acid, and replace oxazolidin-2-one with (S)-4-(4-fluorophenyl)oxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-(4-fluorophenyl)-3-(3-(2-(trifluoromethoxyphenyl) acryloyl)oxazolidin-2-one. LRMS (ESI): 396.08 [M+H]+.
Example 54 (E)-4-(4-fluorophenyl)-3-(3-(2-phenoxyphenyl)acryloyl) oxazolidin-2-one
[0134] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-phenoxyphenyl)acrylic acid, and replace oxazolin-2-one with 4-(4-fluorophenyl)oxazolin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-4-(4-fluorophenyl)-3-(3-(2-phenoxyphenyl)acryloyl)oxazolin-2-one.
[0135] LRMS (ESI): 404.12 [M+H]+.
Example 55 (S, E)-4-(4-fluorophenyl)-3-(3-(2-phenoxyphenyl)acryloyl) oxazolidin-2-one
[0136] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-phenoxyphenyl)acrylic acid, and replace oxazolidin-2-one with (S)-4-(4-fluorophenyl)oxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-(4-fluorophenyl)-3-(3-(2-phenoxyphenyl)acryloyl) oxazolidin-2-one. LRMS (ESI): 404.12 [M+H]+.
Example 56 (E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)-4-(4-fluorophenyl) oxazolidin-2-one
[0137] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-([1,1-biphenyl]-3-yl) acrylic acid, and replace oxazolidin-2-one with 4-(4-fluorophenyl)oxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)-4-(4-fluorophenyl) oxazolidin-2-one. LRMS (ESI): 388.13 [M+H]+.
Example 57 (E)-4-benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one
[0138] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolin-2-one with 4-benzyloxazolin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-4-benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolin-2-one (yield 86.9%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.91-7.82 (m, 2H), 7.76 (td, J=7.4, 2.0 Hz, 1H), 7.64 (d, J=15.0 Hz, 1H), 7.49 (td, J=7.5, 2.1 Hz, 1H), 7.33-7.23 (m, 3H), 7.24-7.14 (m, 3H), 4.64 (p, J=7.0 Hz, 1H), 4.56 (dd, J=11.3, 7.0 Hz, 1H), 4.33 (dd, J=11.3, 6.8 Hz, 1H), 3.17 (dd, J=12.4, 6.9 Hz, 1H), 2.91 (dd, J=12.4, 6.9 Hz, 1H). LRMS (ESI): 376.11 [M+H]+.
Example 58 (S, E)-4-benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one
[0139] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolin-2-one with (S)-4-benzyloxazolin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolin-2-one (yield 86.9%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.91-7.82 (m, 2H), 7.76 (td, J=7.4, 2.0 Hz, 1H), 7.64 (d, J=15.0 Hz, 1H), 7.49 (td, J=7.5, 2.1 Hz, 1H), 7.33-7.23 (m, 3H), 7.24-7.14 (m, 3H), 4.64 (p, J=7.0 Hz, 1H), 4.56 (dd, J=11.3, 7.0 Hz, 1H), 4.33 (dd, J=11.3, 6.8 Hz, 1H), 3.17 (dd, J=12.4, 6.9 Hz, 1H), 2.91 (dd, J=12.4, 6.9 Hz, 1H). LRMS (ESI): 376.11 [M+H]+.
Example 59 (R, E)-4-benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one
[0140] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolin-2-one with (R)-4-benzyloxazolin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (R, E)-4-benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolin-2-one (yield 86.4%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.91-7.82 (m, 2H), 7.76 (td, J=7.4, 2.0 Hz, 1H), 7.64 (d, J=15.0 Hz, 1H), 7.49 (td, J=7.5, 2.1 Hz, 1H), 7.33-7.23 (m, 3H), 7.24-7.14 (m, 3H), 4.64 (p, J=7.0 Hz, 1H), 4.56 (dd, J=11.3, 7.0 Hz, 1H), 4.33 (dd, J=11.3, 6.8 Hz, 1H), 3.17 (dd, J=12.4, 6.9 Hz, 1H), 2.91 (dd, J=12.4, 6.9 Hz, 1H). LRMS (ESI): 376.11 [M+H]+.
Example 60 (E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)-4-benzyloxazolidin-2-one
[0141] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-([1,1-biphenyl]-3-yl) acrylic acid, and replace oxazolidin-2-one with 4-benzyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)-4-benzyloxazolidin-2-one (yield 79.0%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.95 (s, 1H), 7.93 (d, J=15.8 Hz, 1H), 7.87 (d, J=15.8 Hz, 1H), 7.78-7.74 (m, 1H), 7.74-7.68 (m, 3H), 7.57 (t, J=7.7 Hz, 1H), 7.50 (dd, J=8.2, 7.0 Hz, 2H), 7.44-7.38 (m, 1H), 7.36-7.30 (m, 2H), 7.29-7.21 (m, 3H), 4.79 (td, J=7.7, 3.8 Hz, 1H), 4.40 (t, J=8.5 Hz, 1H), 4.24 (dd, J=8.7, 2.9 Hz, 1H), 3.11 (dd, J=13.6, 3.4 Hz, 1H), 3.02 (dd, J=13.6, 7.5 Hz, 1H). LRMS (ESI): 384.0 [M+H].sup.+.
Example 61 (S, E)-4-isopropyl-3-(3-(2-(trifluoromethyl)phenyl)acryloyl) oxazolidin-2-one
[0142] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolidin-2-one with (S)-4-isopropyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-isopropyl-3-(3-(2-(trifluoromethylphenyl)acryloyl) oxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 8.22 (dq, J=15.5, 2.3 Hz, 1H), 7.92 (d, J=15.5 Hz, 1H), 7.86 (d, J=7.8 Hz, 1H), 7.71 (dd, J=7.8, 1.3 Hz, 1H), 7.58 (td, J=7.8, 1.5 Hz, 1H), 7.49 (tt, J=7.6, 1.0 Hz, 1H), 4.60-4.54 (m, 1H), 4.34 (dd, J=9.2, 8.3 Hz, 1H), 4.27 (dd, J=9.1, 3.2 Hz, 1H), 2.49 (pd, J=7.0, 3.9 Hz, 1H), 0.95 (dd, J=15.0, 7.0 Hz, 6H); LRMS (ESI): 328.11 [M+H].sup.+.
Example 62 (S, E)-4-isopropyl-3-(3-(4-(trifluoromethyl)phenyl)acryloyl) oxazolidin-2-one
[0143] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(4-trifluoromethylphenyl) acrylic acid, and replace oxazolidin-2-one with (S)-4-isopropyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-isopropyl-3-(3-(4-(trifluoromethylphenyl)acryloyl) oxazolidin-2-one. LRMS (ESI): 328.11 [M+H].sup.+.
Example 63 (S, E)-4-isopropyl-3-(3-(3-(trifluoromethyl)phenyl)acryloyl) oxazolidin-2-one
[0144] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(3-trifluoromethylphenyl) acrylic acid, and replace oxazolidin-2-one with (S)-4-isopropyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-isopropyl-3-(3-(trifluoromethylphenyl)acryloyl)oxazolidin-2-one. LRMS (ESI): 328.11 [M+H].sup.+.
Example 64 (S, E)-4-isopropyl-3-(3-(3-trifluoromethoxyphenyl)acryloyl) oxazolidin-2-one
[0145] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(3-trifluoromethoxyphenyl) acrylic acid, and replace oxazolidin-2-one with (S)-4-isopropyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-isopropyl-3-(3-(3-trifluoromethoxyphenyl)acryloyl) oxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 7.96 (d, J=15.7 Hz, 1H), 7.80 (d, J=15.7 Hz, 1H), 7.56 (dt, J=7.8, 1.2 Hz, 1H), 7.47-7.40 (m, 2H), 7.29-7.21 (m, 1H), 4.57 (ddd, J=8.3, 4.0, 3.2 Hz, 1H), 4.34 (dd, J=9.1, 8.3 Hz, 1H), 4.27 (dd, J=9.1, 3.2 Hz, 1H), 2.46 (pt, J=7.0, 3.5 Hz, 1H), 0.94 (dd, J=17.4, 7.0 Hz, 6H); LRMS (ESI): 344.10 [M+H].sup.+.
Example 65 (S, E)-4-isopropyl-3-(3-(2-trifluoromethoxyphenyl)acryloyl) oxazolidin-2-one
[0146] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethoxyphenyl) acrylic acid, and replace oxazolidin-2-one with (S)-4-isopropyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-isopropyl-3-(3-(2-trifluoromethoxyphenyl)acryloyl) oxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 8.11 (d, J=15.9 Hz, 1H), 7.99 (d, J=15.8 Hz, 1H), 7.81 (dd, J=7.8, 1.7 Hz, 1H), 7.44 (ddd, J=8.2, 7.4, 1.7 Hz, 1H), 7.36-7.28 (m, 2H), 4.57 (ddd, J=8.2, 3.9, 3.1 Hz, 1H), 4.34 (dd, J=9.1, 8.3 Hz, 1H), 4.27 (dd, J=9.1, 3.1 Hz, 1H), 2.48 (heptd, J=7.0, 3.9 Hz, 1H), 0.97 (d, J=7.0 Hz, 3H), 0.93 (d, J=7.0 Hz, 3H); LRMS (ESI): 344.10 [M+H].sup.+.
Example 66 (S, E)-4-isopropyl-3-(3-(4-trifluoromethoxyphenyl)acryloyl) oxazolidin-2-one
[0147] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(4-trifluoromethoxyphenyl) acrylic acid, and replace oxazolidin-2-one with (S)-4-isopropyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-isopropyl-3-(3-(4-trifluoromethoxyphenyl)acryloyl) oxazolidin-2-one. LRMS (ESI): 344.10 [M+H].sup.+.
Example 67 (S, E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)-4-isopropyloxazolidin-2-one
[0148] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-([1,1-biphenyl]-3-yl) acrylic acid, and replace oxazolidin-2-one with (S)-4-isopropyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)-4-isopropyloxazolidin-2-one. LRMS (ESI): 336.15 [M+H].sup.+.
Example 68 (S, E)-3-(3-(4-fluoro-2-(trifluoromethyl)phenyl)acryloyl)-4-isopropyloxazolidin-2-one
[0149] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(4-fluoro-2-(trifluoromethyl)phenyl)acrylic acid, and replace oxazolidin-2-one with (S)-4-isopropyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-(4-fluoro-2-(trifluoromethyl)phenyl)acryloyl)-4-isopropyloxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 8.14 (d, J=15.5 Hz, 1H), 7.88 (d, J=14.7 Hz, 2H), 7.60-7.36 (m, 1H), 7.30 (d, J=8.5 Hz, 1H), 4.57 (dd, J=8.0, 3.9 Hz, 1H), 4.40-4.18 (m, 2H), 2.64-2.34 (m, 1H), 0.95 (dd, J=16.0, 7.0 Hz, 8H); LRMS (ESI): 346.10 [M+H].sup.+.
Example 69 (S, E)-3-(3-(benzofuran-2-yl)acryloyl)-4-isopropyloxazolidin-2-one
[0150] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(benzofuran-2-yl)acrylic acid, and replace oxazolin-2-one with (S)-4-isopropyloxazolin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-(benzofuran-2-yl)acryloyl)-4-isopropyloxazolin-2-one. .sup.1H NMR (400 MHz, Methylene Chloride-d.sub.2) 7.96 (dd, J=15.4, 0.6 Hz, 1H), 7.70 (d, J=15.4 Hz, 1H), 7.62 (ddd, J=7.8, 1.3, 0.7 Hz, 1H), 7.54 (dq, J=8.4, 0.9 Hz, 1H), 7.42-7.36 (m, 1H), 7.26 (ddd, J=8.1, 7.2, 1.0 Hz, 1H), 7.05 (s, 1H), 4.55 (ddd, J=8.2, 4.0, 3.2 Hz, 1H), 4.33 (dd, J=9.1, 8.2 Hz, 1H), 4.26 (dd, J=9.1, 3.2 Hz, 1H), 2.00 (s, 1H), 0.95 (d, J=7.0 Hz, 3H), 0.91 (d, J=6.9 Hz, 3H); LRMS (ESI): 300.12 [M+H].sup.+.
Example 70 (S, E)-3-(3-(benzo [b]thiophen-2-yl)acryloyl)-4-isopropyloxazolidin-2-one
[0151] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(benzo [b]thiophen-2-yl) acrylic acid, and replace oxazolidin-2-one with (S)-4-isopropyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-(benzo [b]thiophen-2-yl)acryloyl)-4-isopropyloxazolidin-2-one. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.09-8.03 (m, 1H), 8.02-7.98 (m, 1H), 7.92-7.87 (m, 2H), 7.69 (d, J=15.4 Hz, 1H), 7.44 (pd, J=7.1, 1.4 Hz, 2H), 4.49 (dt, J=7.4, 3.7 Hz, 1H), 4.41-4.33 (m, 2H), 1.32-1.19 (m, 1H), 0.86 (dd, J=26.2, 6.9 Hz, 6H); LRMS (ESI): 316.09 [M+H].sup.+.
Example 71 (S, E)-4-isopropyl-3-(3-(naphthalen-1-yl)acryloyl)oxazolidin-2-one
[0152] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(naphthalen-1-yl)acrylic acid, and replace oxazolidin-2-one with (S)-4-isopropyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-isopropyl-3-(3-(naphthalen-1-yl)acryloyl)oxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 8.74 (d, J=15.5 Hz, 1H), 8.28 (d, J=8.4 Hz, 1H), 8.06 (d, J=15.5 Hz, 1H), 7.95 (dd, J=7.7, 3.5 Hz, 2H), 7.91 (dd, J=7.7, 1.3 Hz, 1H), 7.61 (ddd, J=8.5, 6.8, 1.5 Hz, 1H), 7.58-7.51 (m, 2H), 4.63 (dt, J=8.3, 3.5 Hz, 1H), 4.37 (t, J=8.7 Hz, 1H), 4.30 (dd, J=9.1, 3.1 Hz, 1H), 2.54 (pd, J=7.0, 4.0 Hz, 1H), 1.01 (d, J=7.0 Hz, 3H), 0.98 (d, J=6.9 Hz, 3H); LRMS (ESI): 310.10 [M+H].sup.+.
Example 72 (S, E)-3-(3-(benzo [d][1,3]dioxolan-5-yl)acryloyl)-4-isopropyloxazolidin-2-one
[0153] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(benzo [d][1,3]dioxolan-5-yl)acrylic acid, and replace oxazolidin-2-one with (S)-4-isopropyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-(benzo [d][1,3]dioxolan-5-yl)acryloyl)-4-isopropyloxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 7.77 (d, J=0.9 Hz, 2H), 7.15 (d, J=1.7 Hz, 1H), 7.10 (dd, J=8.0, 1.7 Hz, 1H), 6.82 (d, J=8.0 Hz, 1H), 6.02 (s, 2H), 4.56 (ddd, J=8.2, 4.0, 3.1 Hz, 1H), 4.31 (dd, J=9.1, 8.3 Hz, 1H), 4.25 (dd, J=9.0, 3.2 Hz, 1H), 2.46 (pd, J=7.0, 3.9 Hz, 1H), 0.96 (d, J=7.0 Hz, 3H), 0.91 (d, J=6.9 Hz, 3H); LRMS (ESI): 304.11 [M+H].sup.+.
Example 73 (E)-3-(3-(benzo [d][1,3]dioxolan-5-yl)acryloyl)-4,4-dimethyloxazolidin-2-one
[0154] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(benzo [d][1,3]dioxolan-5-yl)acrylic acid, and replace oxazolidin-2-one with 4,4-dimethyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(benzo [d][1,3]dioxolan-5-yl)acryloyl)-4,4-dimethyloxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 7.71 (d, J=15.6 Hz, 1H), 7.56 (d, J=15.5 Hz, 1H), 7.12 (d, J=1.7 Hz, 1H), 7.07 (dd, J=8.0, 1.7 Hz, 1H), 6.81 (d, J=8.0 Hz, 1H), 6.01 (s, 2H), 4.05 (s, 2H), 1.64 (s, 6H); LRMS (ESI): 290.10 [M+H].sup.+.
Example 74 (E)-4,4-dimethyl-3-(3-(2-(trifluoromethyl)phenyl)acryloyl) oxazolidin-2-one
[0155] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolidin-2-one with 4,4-dimethyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-4,4-dimethyl-3-(3-(2-(trifluoromethylphenyl)acryloyl) oxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 8.15 (d, J=15.4 Hz, 1H), 7.83 (d, J=7.8 Hz, 1H), 7.79-7.65 (m, 2H), 7.53 (dt, J=37.3, 7.7 Hz, 2H), 4.08 (s, 2H), 1.66 (s, 6H); LRMS (ESI): 314.09 [M+H].sup.+.
Example 75 (E)-4,4-dimethyl-3-(3-(3-(trifluoromethoxy)phenyl)acryloyl) oxazolidin-2-one
[0156] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(3-trifluoromethoxyphenyl) acrylic acid, and replace oxazolidin-2-one with 4,4-dimethyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-4,4-dimethyl-3-(3-(trifluoromethoxyphenyl)acryloyl) oxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 7.73 (s, 2H), 7.53 (dt, J=7.7, 1.2 Hz, 1H), 7.45-7.38 (m, 2H), 7.25-7.22 (m, 1H), 4.08 (s, 2H), 1.65 (s, 6H); LRMS (ESI): 330.09 [M+H].sup.+.
Example 76 (E)-4,4-dimethyl-3-(3-(2-(trifluoromethoxy)phenyl)acryloyl) oxazolidin-2-one
[0157] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethoxyphenyl) acrylic acid, and replace oxazolidin-2-one with 4,4-dimethyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-4,4-dimethyl-3-(3-(2-(trifluoromethoxyphenyl)acryloyl) oxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 8.04 (d, J=15.8 Hz, 1H), 7.88-7.66 (m, 2H), 7.47-7.38 (m, 1H), 7.38-7.20 (m, 2H), 4.08 (s, 2H), 1.66 (s, 6H); LRMS (ESI): 330.09 [M+H].sup.+.
Example 77 (E)-3-(3-(4-fluoro-2-(trifluoromethyl)phenyl)acryloyl)-4,4-dimethyloxazolidin-2-one
[0158] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(4-fluoro-2-trifluoromethylphenyl)acrylic acid, and replace oxazolidin-2-one with 4,4-dimethyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-fluoro-2-(trifluoromethylphenyl)acryloyl)-4,4-dimethyloxazolidin-2-one. .sup.1H NMR (400 MHz, Chloroform-d) 8.07 (d, J=15.6 Hz, 1H), 7.84 (dd, J=8.8, 5.4 Hz, 1H), 7.67 (d, J=15.5 Hz, 1H), 7.45-7.38 (m, 1H), 7.27 (d, J=6.5 Hz, 1H), 4.08 (s, 2H), 1.66 (s, 6H); LRMS (ESI): 332.12 [M+H].sup.+.
Example 78 (E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl) thiazolidin-2-one
[0159] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-([1,1-biphenyl]-3-yl) acrylic acid, and replace oxazolidin-2-one with thiazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl) thiazolidin-2-one (yield 89.0%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=15.0 Hz, 1H), 7.73 (dd, J=7.5, 2.0 Hz, 2H), 7.66-7.44 (m, 7H), 7.44-7.34 (m, 1H), 3.70 (t, J=6.1 Hz, 2H), 3.55 (t, J=6.0 Hz, 2H). LRMS (ESI): 310.08 [M+H].sup.+.
Example 79 (E)-3-(3-(2-phenoxyphenyl)acryloyl) thiazolidin-2-one
[0160] Replace (E)-3-(2-phenoxyphenyl)acrylic acid with (E)-3-(2-phenoxyphenyl)acrylic acid, and replace oxazolidin-2-one with thiazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(2-phenoxyphenyl)acryloyl) thiazolidin-2-one (yield 89.6%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.94 (dd, J=15.0, 0.9 Hz, 1H), 7.68-7.60 (m, 2H), 7.46 (td, J=7.5, 2.0 Hz, 1H), 7.44-7.34 (m, 2H), 7.23-7.09 (m, 2H), 7.12-7.01 (m, 3H), 3.70 (t, J=6.1 Hz, 2H), 3.55 (t, J=6.0 Hz, 2H). LRMS (ESI): 326.08 [M+H].sup.+.
Example 80 (E)-3-(3-(2-trifluoromethylphenyl)acryloyl) thiazolidine-2-one
[0161] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, replace oxazolidin-2-one with thiazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(2-trifluoromethylphenyl)acryloyl) thiazolidin-2-one (yield 90.6%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.86-7.79 (m, 1H), 7.76 (td, J=7.5, 2.0 Hz, 1H), 7.69-7.55 (m, 2H), 7.47 (td, J=7.4, 2.1 Hz, 1H), 7.30-7.23 (m, 1H), 3.70 (t, J=6.2 Hz, 2H), 3.55 (t, J=6.2 Hz, 2H). LRMS (ESI): 302.04 [M+H].sup.+.
Example 81 (E)-3-(3-(thiphen-2-yl)acryloyl) thiazolidin-2-one
[0162] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(thiphen-2-yl)acrylic acid, replace oxazolidin-2-one with thiazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(thiphen-2-yl)acryloyl) thiazolidin-2-one (yield 85.1%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.86-7.75 (m, 2H), 7.70 (dd, J=7.4, 1.6 Hz, 1H), 7.60 (d, J=15.0 Hz, 1H), 7.20 (t, J=7.4 Hz, 1H), 3.70 (t, J=6.1 Hz, 2H), 3.55 (t, J=6.0 Hz, 2H). LRMS (ESI): 240.01 [M+H].sup.+.
Example 83 (S, E)-4-phenyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d.SUB.2
[0163] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolin-2-one with (S)-4-phenyloxazolin-2-one-5,5-d2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-phenyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolin-2-one-5,5-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.94 (d, J=7.8 Hz, 1H), 7.89-7.77 (m, 4H), 7.67 (t, J=7.6 Hz, 1H), 7.44-7.30 (m, 5H), 5.57 (s, 1H). LRMS (ESI): 364.11 [M+H].sup.+.
Example 84 (S, E)-4-phenyl-3-(3-(2-trifluoromethoxyphenyl)acryloyl) oxazolidin-2-one-5,5-d2
[0164] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethoxyphenyl) acrylic acid, and replace oxazolin-2-one with (S)-4-phenyloxazolin-2-one-5,5-d2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-phenyl-3-(3-(2-trifluoromethoxyphenyl)acryloyl)oxazolin-2-one-5,5-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.95 (d, J=15.0 Hz, 1H), 7.70-7.60 (m, 2H), 7.39-7.28 (m, 4H), 7.28-7.18 (m, 2H), 7.02 (t, J=7.1 Hz, 2H), 5.50 (s, 1H). LRMS (ESI): 380.11 [M+H].sup.+.
Example 85 (S, E)-4-phenyl-3-(3-(2-phenoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d.SUB.2
[0165] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-phenoxyphenyl)acrylic acid, and replace oxazolin-2-one with (S)-4-phenyloxazolin-2-one-5,5-d2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-phenyl-3-(3-(2-phenoxyphenyl)acryloyl)oxazolin-2-one-5,5-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.95 (d, J=15.0 Hz, 1H), 7.68-7.58 (m, 2H), 7.46 (td, J=7.4, 2.0 Hz, 1H), 7.42-7.19 (m, 7H), 7.19-7.09 (m, 1H), 7.09-7.01 (m, 2H), 5.50 (s, 1H). LRMS (ESI): 388.14 [M+H].sup.+.
Example 86 (S, E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one-5,5-d.SUB.2
[0166] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-([1,1-biphenyl]-3-yl) acrylic acid, and replace oxazolidin-2-one with (S)-4-isopropyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)-4-phenyloxazolidin-2-one-5,5-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=15.0 Hz, 1H), 7.73 (dd, J=7.6, 2.0 Hz, 3H), 7.62 (dt, J=7.6, 2.1 Hz, 1H), 7.54-7.47 (m, 3H), 7.47-7.32 (m, 7H), 7.32-7.25 (m, 1H), 7.24 (ddt, J=5.3, 3.9, 1.6 Hz, 1H), 5.50 (s, 1H). LRMS (ESI): 372.15 [M+H].sup.+.
Example 87 (S, E)-4-phenyl-3-(3-(3-phenoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d.SUB.2
[0167] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(3-phenoxyphenyl)acrylic acid, and replace oxazolin-2-one with (S)-4-phenyloxazolin-2-one-5,5-d2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-phenyl-3-(3-(3-phenoxyphenyl)acryloyl)oxazolin-2-one-5,5-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=15.1 Hz, 1H), 7.44-7.29 (m, 9H), 7.29-7.20 (m, 2H), 7.14 (tt, J=7.4, 2.0 Hz, 1H), 7.05 (dd, J=7.5, 2.0 Hz, 2H), 6.88 (dp, J=4.1, 2.1 Hz, 2H), 5.50 (s, 1H). LRMS (ESI): 388.14 [M+H].sup.+.
Example 88 (E)-4-phenyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d.SUB.2
[0168] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolin-2-one with 4-phenyloxazolin-2-one-5,5-d2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-4-phenyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolin-2-one-5,5-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.94 (d, J=7.8 Hz, 1H), 7.89-7.77 (m, 4H), 7.67 (t, J=7.6 Hz, 1H), 7.44-7.30 (m, 5H), 5.57 (s, 1H). LRMS (ESI): 364.11 [M+H].sup.+.
Example 89 (E)-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one-4,4,5-d4
[0169] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolidin-2-one with oxazolidin-2-one-4,4,5-d4. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one-4,4,5-d4. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.00-7.89 (m, 2H), 7.76 (td, J=7.5, 2.1 Hz, 1H), 7.64 (d, J=15.0 Hz, 1H), 7.35 (td, J=7.5, 2.0 Hz, 1H), 7.27-7.19 (m, 1H). LRMS (ESI): 290.09 [M+H].sup.+.
Example 90 (E)-3-(3-(2-methoxyphenyl)acryloyl)oxazolidin-2-one-4,4,5-d4
[0170] Replace (E)-3-(o-methoxyphenyl)acrylic acid with (E)-3-(2-methoxyphenyl)acrylic acid, and replace oxazolidin-2-one with oxazolidin-2-one-4,4,5-d4. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(2-methoxyphenyl)acryloyl)oxazolidin-2-one-4,4,5-d4. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.95 (dd, J=15.0, 1.0 Hz, 1H), 7.70-7.60 (m, 2H), 7.49 (td, J=7.5, 2.0 Hz, 1H), 7.11-6.97 (m, 2H), 3.91 (s, 3H). LRMS (ESI): 252.11 [M+H].sup.+.
Example 91 (E)-3-(3-(3-methoxyphenyl)acryloyl)oxazolidin-2-one-4,4,5-d4
[0171] Replace (E)-3-(o-methoxyphenyl)acrylic acid with (E)-3-(3-methoxyphenyl)acrylic acid, and replace oxazolidin-2-one with oxazolidin-2-one-4,4,5-d4. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(3-methoxyphenyl)acryloyl)oxazolidin-2-one-4,4,5-d4. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=15.0 Hz, 1H), 7.41-7.27 (m, 3H), 7.04 (t, J=1.6 Hz, 1H), 6.86-6.77 (m, 1H), 3.73 (s, 3H). LRMS (ESI): 252.11 [M+H].sup.+.
Example 92 (E)-3-(3-(4-methoxyphenyl)acryloyl)oxazolidin-2-one-4,4,5-d4
[0172] Replace (E)-3-(o-methoxyphenyl)acrylic acid with (E)-3-(4-methoxyphenyl)acrylic acid, and replace oxazolidin-2-one with oxazolidin-2-one-4,4,5-d4. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-methoxyphenyl)acryloyl)oxazolidin-2-one-4,4,5-d4. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=15.0 Hz, 1H), 7.72-7.64 (m, 2H), 7.37 (dt, J=15.2, 1.0 Hz, 1H), 7.10-7.02 (m, 2H), 3.79 (s, 3H). LRMS (ESI): 252.11 [M+H].sup.+.
Example 93 (E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)oxazolidin-2-one-4,4,5-d4
[0173] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-([1,1-biphenyl]-3-yl) acrylic acid, and replace oxazolidin-2-one with oxazolidin-2-one-4,4,5-d4. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)oxazolidin-2-one-4,4,5-d4. .sup.1HNMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=15.0 Hz, 1H), 7.73 (dd, J=7.6, 2.0 Hz, 3H), 7.62 (dt, J=7.6, 2.1 Hz, 1H), 7.54-7.43 (m, 4H), 7.43-7.32 (m, 2H). LRMS (ESI): 298.13 [M+H].sup.+.
Example 94 (E)-3-(3-(3-phenoxyphenyl)acryloyl)oxazolidin-2-one-4,4,5-d4
[0174] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(3-phenoxyphenyl)acrylic acid, and replace oxazolidin-2-one with oxazolidin-2-one-4,4,5-d4. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(3-phenoxyphenyl)acryloyl)oxazolidin-2-one-4,4,5-d4. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=15.1 Hz, 1H), 7.44-7.31 (m, 4H), 7.29 (t, J=7.7 Hz, 1H), 7.14 (tt, J=7.5, 2.0 Hz, 1H), 7.09-7.01 (m, 2H), 6.88 (dp, J=4.1, 2.1 Hz, 2H). LRMS (ESI): 314.13 [M+H].sup.+.
Example 95 (E)-3-(3-(4-methoxyphenyl)acryloyl)oxazolidin-2-one-4,4-d.SUB.2
[0175] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(4-methoxyphenyl)acrylic acid, and replace oxazolidin-2-one with oxazolidin-2-one-4,4-d2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-methoxyphenyl)acryloyl)oxazolidin-2-one-4,4-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=15.0 Hz, 1H), 7.72-7.64 (m, 2H), 7.37 (dt, J=15.2, 1.0 Hz, 1H), 7.10-7.02 (m, 2H), 4.30 (s, 2H), 3.79 (s, 3H). LRMS (ESI): 250.10 [M+H].sup.+.
Example 96 (E)-3-(3-(4-methoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d.SUB.2
[0176] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(4-methoxyphenyl)acrylic acid, and replace oxazolidin-2-one with oxazolidin-2-one-5,5-d2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(4-methoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=15.0 Hz, 1H), 7.72-7.64 (m, 2H), 7.37 (dt, J=15.1, 1.0 Hz, 1H), 7.10-7.02 (m, 2H), 3.80 (s, 2H), 3.79 (s, 3H). LRMS (ESI): 250.10 [M+H].sup.+.
Example 97 (E)-3-(3-(3-phenoxyphenyl)acryloyl)oxazolidin-2-one-4,4-d.SUB.2
[0177] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(3-phenoxyphenyl)acrylic acid, and replace oxazolidin-2-one with oxazolidin-2-one-4,4-d2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(3-phenoxyphenyl)acryloyl)oxazolidin-2-one-4,4-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=15.1 Hz, 1H), 7.44-7.31 (m, 4H), 7.29 (t, J=7.7 Hz, 1H), 7.14 (tt, J=7.5, 2.0 Hz, 1H), 7.09-7.01 (m, 2H), 6.88 (dp, J=5.7, 2.1 Hz, 2H), 4.30 (s, 2H). LRMS (ESI): 312.12 [M+H].sup.+.
Example 98 (E)-3-(3-(3-phenoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d.SUB.2
[0178] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(3-phenoxyphenyl)acrylic acid, and replace oxazolidin-2-one with oxazolidin-2-one-5,5-d2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(3-phenoxyphenyl)acryloyl)oxazolidin-2-one-5,5-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=15.1 Hz, 1H), 7.44-7.31 (m, 4H), 7.29 (t, J=7.7 Hz, 1H), 7.14 (tt, J=7.5, 2.0 Hz, 1H), 7.09-7.01 (m, 2H), 6.88 (dp, J=5.7, 2.1 Hz, 2H), 3.80 (s, 2H). LRMS (ESI): 312.12 [M+H].sup.+.
Example 99 (E)-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d2
[0179] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolidin-2-one with oxazolidin-2-one-5,5-d2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.00-7.89 (m, 2H), 7.76 (td, J=7.5, 2.1 Hz, 1H), 7.64 (d, J=15.0 Hz, 1H), 7.35 (td, J=7.5, 2.0 Hz, 1H), 7.23 (ddd, J=7.6, 2.1, 1.0 Hz, 1H), 3.80 (s, 2H). LRMS (ESI): 288.07 [M+H].sup.+.
Example 100 (E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)oxazolidin-2-one-5,5-d.SUB.2
[0180] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-([1,1-biphenyl]-3-yl) acrylic acid, and replace oxazolidin-2-one with oxazolidin-2-one-5,5-di. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)oxazolidin-2-one-5,5-di. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=15.0 Hz, 1H), 7.73 (dq, J=8.3, 2.1 Hz, 3H), 7.62 (dt, J=7.6, 2.1 Hz, 1H), 7.54-7.43 (m, 4H), 7.39 (s, 1H), 7.44-7.32 (m, 1H), 3.80 (s, 2H). LRMS (ESI): 296.12 [M+H].sup.+.
Example 101 (E)-4,4-dimethyl-3-(3-(2-(trifluoromethyl)phenyl)acryloyl) oxazolidin-2-one-5,5-d.SUB.2
[0181] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolidin-2-one with 4,4-dimethyloxazolidin-2-one-5,5-d.sub.2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-4,4-dimethyl-3-(3-(2-(trifluoromethylphenyl)acryloyl) oxazolidin-2-one-5,5-d.sub.2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.00-7.89 (m, 2H), 7.76 (td, J=7.5, 2.0 Hz, 1H), 7.64 (d, J=15.0 Hz, 1H), 7.35 (td, J=7.5, 2.1 Hz, 1H), 7.23 (ddd, J=7.5, 2.1, 1.0 Hz, 1H), 1.29 (s, 6H). LRMS (ESI): 316.12 [M+H].sup.+.
Example 102 (E)-4-(4-fluorophenyl)-3-(3-(2-(trifluoromethylphenyl)acryloyl) oxazolidin-2-one-5,5-d.SUB.2
[0182] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolin-2-one with 4-(4-fluorophenyl)oxazolin-2-one-5,5-d2.
[0183] The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-4-(4-fluorophenyl)-3-(3-(2-(trifluoromethylphenyl) acryloyl)oxazolin-2-one-5,5-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.00-7.89 (m, 2H), 7.76 (td, J=7.5, 2.1 Hz, 1H), 7.64 (d, J=15.0 Hz, 1H), 7.35 (td, J=7.5, 2.1 Hz, 1H), 7.27-7.12 (m, 5H), 5.50 (s, 1H). LRMS (ESI): 382.10 [M+H].sup.+.
Example 103 (S, E)-4-(4-fluorophenyl)-3-(3-(2-(trifluoromethylphenyl) acryloyl)oxazolidin-2-one-5,5-d.SUB.2
[0184] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolin-2-one with (S)-4-(4-fluorophenyl)oxazolin-2-one-5,5-d2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-(4-fluorophenyl)-3-(3-(2-(trifluoromethylphenyl)acryloyl)oxazolin-2-one-5,5-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.00-7.89 (m, 2H), 7.76 (td, J=7.5, 2.1 Hz, 1H), 7.64 (d, J=15.0 Hz, 1H), 7.35 (td, J=7.5, 2.1 Hz, 1H), 7.27-7.12 (m, 5H), 5.50 (s, 1H). LRMS (ESI): 382.10 [M+H].sup.+.
Example 104 (E)-4-benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolidin-2-one-5,5-d.SUB.2
[0185] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolin-2-one with 4-benzyloxazolin-2-one-5,5-d2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-4-benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolin-2-one-5,5-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.00-7.89 (m, 2H), 7.76 (td, J=7.5, 2.1 Hz, 1H), 7.64 (d, J=15.0 Hz, 1H), 7.35 (td, J=7.5, 2.1 Hz, 1H), 7.33-7.14 (m, 6H), 4.60 (t, J=5.3 Hz, 1H), 3.04 (dd, J=12.4, 5.3 Hz, 1H), 2.78 (dd, J=12.4, 5.3 Hz, 1H). LRMS (ESI): 378.12 [M+H].sup.+.
Example 105 (S, E)-4-benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl) oxazolidin-2-one-5,5-d.SUB.2
[0186] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethylphenyl) acrylic acid, and replace oxazolin-2-one with (S)-4-benzyloxazolin-2-one-5,5-d2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-benzyl-3-(3-(2-trifluoromethylphenyl)acryloyl)oxazolin-2-one-5,5-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.00-7.89 (m, 2H), 7.76 (td, J=7.5, 2.1 Hz, 1H), 7.64 (d, J=15.0 Hz, 1H), 7.35 (td, J=7.5, 2.1 Hz, 1H), 7.33-7.14 (m, 6H), 4.60 (t, J=5.3 Hz, 1H), 3.04 (dd, J=12.4, 5.3 Hz, 1H), 2.78 (dd, J=12.4, 5.3 Hz, 1H). LRMS (ESI): 378.12 [M+H].sup.+.
Example 106 (S, E)-4-(4-fluorophenyl)-3-(3-(2-(trifluoromethoxyphenyl) acryloyl)oxazolidin-2-one-5,5-d.SUB.2
[0187] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-trifluoromethoxyphenyl) acrylic acid, and replace oxazolin-2-one with (S)-4-(4-fluorophenyl)oxazolin-2-one-5,5-d2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-(4-fluorophenyl)-3-(3-(2-(trifluoromethoxyphenyl)acryloyl)oxazolin-2-one-5,5-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.95 (dd, J=15.0, 0.9 Hz, 1H), 7.70-7.60 (m, 2H), 7.28-7.12 (m, 5H), 7.02 (t, J=7.1 Hz, 2H), 5.50 (s, 1H). LRMS (ESI): 398.09 [M+H].
Example 107 (S, E)-4-(4-fluorophenyl)-3-(3-(2-(phenoxyphenyl)acryloyl) oxazolidin-2-one-5,5-d.SUB.2
[0188] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(2-phenoxyphenyl)acrylic acid, replace oxazolidin-2-one with (S)-4-(4-fluorophenyl)oxazolidin-2-one-5,5-d2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-(4-fluorophenyl)-3-(3-(2-(phenoxyphenyl)acryloyl) oxazolidin-2-one-5,5-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.95 (dd, J=15.0, 0.9 Hz, 1H), 7.68-7.58 (m, 2H), 7.46 (td, J=7.4, 2.0 Hz, 1H), 7.44-7.34 (m, 2H), 7.31-7.18 (m, 3H), 7.21-7.10 (m, 3H), 7.14-7.01 (m, 3H), 5.50 (s, 1H). LRMS (ESI): 406.13 [M+H].sup.+.
Example 108 (S, E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)-4-(4-fluorophenyl) oxazolidin-2-one-5,5-d.SUB.2
[0189] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-([1,1-biphenyl]-3-yl) acrylic acid, and replace oxazolidin-2-one with (S)-4-(4-fluorophenyl)oxazolidin-2-one-5,5-d2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-([1,1-biphenyl]-3-yl)acryloyl)-4-(4-fluorophenyl)oxazolidin-2-one-5,5-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=15.0 Hz, 1H), 7.73 (dd, J=7.5, 2.0 Hz, 3H), 7.62 (dt, J=7.6, 2.1 Hz, 1H), 7.54-7.43 (m, 4H), 7.44-7.33 (m, 2H), 7.26-7.12 (m, 4H), 5.50 (s, 1H). LRMS (ESI): 390.13 [M+H].sup.+.
Example 109 (S, E)-4-(4-fluorophenyl)-3-(3-(3-(phenoxyphenyl)acryloyl) oxazolidin-2-one-5,5-d.SUB.2
[0190] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(3-phenoxyphenyl)acrylic acid, replace oxazolidin-2-one with (S)-4-(4-fluorophenyl)oxazolidin-2-one-5,5-d2. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-4-(4-fluorophenyl)-3-(3-(3-(phenoxyphenyl)acryloyl) oxazolidin-2-one-5,5-d2. .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.81 (d, J=15.1 Hz, 1H), 7.44-7.09 (m, 11H), 7.09-7.01 (m, 2H), 6.88 (dp, J=4.1, 2.1 Hz, 2H), 5.50 (s, 1H). LRMS (ESI): 406.13 [M+H].sup.+.
Example 110 (R, E)-5,5-dimethyl-4-phenyl-3-(3-(2-(trifluoromethyl)phenyl) acryloyl)oxazolidin-2-one
[0191] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(o-trifluoromethylphenyl) acrylic acid, and replace oxazolin-2-one with (R)-5,5-dimethyl-4-phenyloxazolin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (R, E)-5,5-dimethyl-4-phenyl-3-(3-(2-(trifluoromethylphenyl)phenyl)acryloyl)oxazolin-2-one (yield 64.2%). .sup.1H NMR (500 MHz, Chloroform-d) 8.16 (dq, J=15.5, 2.3 Hz, 1H), 8.00 (d, J=15.6 Hz, 1H), 7.89 (d, J=7.8 Hz, 1H), 7.69 (d, J=7.8 Hz, 1H), 7.59 (t, J=7.6 Hz, 1H), 7.51-7.47 (m, 1H), 7.42-7.33 (m, 3H), 7.22-7.19 (m, 2H), 5.20 (s, 1H), 1.65 (s, 3H), 1.04 (s, 3H). HRMS (ESI): 390.1315 [M+H].sup.+.
Example 111 (S, E)-5,5-dimethyl-4-phenyl-3-(3-(2-(trifluoromethyl)phenyl) acryloyl)oxazolidin-2-one
[0192] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(o-trifluoromethylphenyl) acrylic acid, and replace oxazolin-2-one with (S)-5,5-dimethyl-4-phenyloxazolin-2-one.
[0193] The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-5,5-dimethyl-4-phenyl-3-(3-(2-(trifluoromethylphenyl)phenyl)acryloyl)oxazolin-2-one (yield 71.5%). .sup.1H NMR (500 MHz, Chloroform-d) 8.19 (ddd, J=7.4, 1.5, 0.6 Hz, 1H), 8.02 (td, J=7.4, 1.6 Hz, 1H), 7.96 (dd, J=7.5, 1.6 Hz, 1H), 7.90 (td, J=7.5, 1.6 Hz, 1H), 7.88-7.82 (m, 1H), 7.62 (d, J=15.0 Hz, 1H), 7.36-7.24 (m, 5H), 5.25-5.21 (m, 1H), 1.46 (d, J=1.6 Hz, 3H), 1.41 (d, J=1.5 Hz, 3H). LRMS (ESI): 390.20 [M+H].sup.+.
Example 112 (R, E)-7-phenyl-6-(3-(2-(trifluoromethyl)phenyl)acryloyl)-4-oxa-6-azaspiro [2.4]heptan-5-one
[0194] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(o-trifluoromethylphenyl) acrylic acid, and replace oxazolin-2-one with (R)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (R, E)-7-phenyl-6-(3-(2-(trifluoromethylphenyl)phenyl) acryloyl)-4-oxa-6-azaspiro [2.4]heptan-5-one (yield 49.2%). .sup.1H NMR (500 MHz, Chloroform-d) 8.18-8.13 (m, 1H), 7.94 (d, J=15.4 Hz, 1H), 7.86 (d, J=7.8 Hz, 1H), 7.68 (dd, J=7.9, 1.3 Hz, 1H), 7.58 (t, J=7.7 Hz, 1H), 7.48 (t, J=7.6 Hz, 1H), 7.43-7.32 (m, 5H), 5.32 (s, 1H), 1.40-1.33 (m, 1H), 1.21-1.13 (m, 1H), 0.98-0.89 (m, 1H), 0.48 (d, J=345.4 Hz, 1H). HRMS (ESI): 388.1156 [M+H].sup.+.
Example 113 (S, E)-7-phenyl-6-(3-(2-(trifluoromethyl)phenyl)acryloyl)-4-oxa-6-azaspiro [2.4]heptan-5-one
[0195] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(o-trifluoromethylphenyl) acrylic acid, and replace oxazolin-2-one with (S)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-7-phenyl-6-(3-(2-(trifluoromethylphenyl)phenyl) acryloyl)-4-oxa-6-azaspiro [2.4]heptan-5-one (yield 47.2%). .sup.1H NMR (500 MHz, Chloroform-d) 8.19 (ddd, J=7.4, 1.6, 0.6 Hz, 1H), 8.02 (td, J=7.4, 1.6 Hz, 1H), 7.96 (dd, J=7.5, 1.6 Hz, 1H), 7.90 (td, J=7.5, 1.6 Hz, 1H), 7.88-7.82 (m, 1H), 7.62 (d, J=15.0 Hz, 1H), 7.37-7.24 (m, 5H), 5.20 (d, J=0.7 Hz, 1H), 1.66-1.55 (m, 2H), 1.55-1.44 (m, 2H). LRMS (ESI): 388.12 [M+H].sup.+.
Example 114 (E)-5-phenyl-1-(3-(2-(trifluoromethyl)phenyl)acryloyl) imidazolidine-2,4-dione
[0196] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(m-methoxyphenyl), and replace oxazolin-2-one with 5-phenylimidazolidine-2,4-dione. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (E)-5-phenyl-1-(3-(2-(trifluoromethyl)phenyl)acryloyl) imidazolidine-2,4-dione (yield 62.8%). .sup.1H NMR (400 MHz, DMSO-d.sub.6) 11.95 (s, 1H), 7.99-7.92 (m, 2H), 7.91-7.84 (m, 1H), 7.82-7.76 (m, 2H), 7.67-7.62 (m, 1H), 7.41 (d, J=4.3 Hz, 4H), 7.39-7.34 (m, 1H), 5.67 (s, 1H). HRMS (ESI): 375.0952 [M+H].sup.+.
Example 115 (R, E)-6-(3-(3-methoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one
[0197] Replace (E)-3-(o-methoxyphenyl)acrylic acid with (E)-3-(methoxyphenyl)acrylic acid, and replace oxazolin-2-one with (R)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (R, E)-6-(3-(3-methoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one (yield 43.2%). .sup.1H NMR (500 MHz, Chloroform-d) 7.93 (d, J=15.7 Hz, 1H), 7.75 (d, J=15.8 Hz, 2H), 7.40-7.25 (m, 8H), 7.19 (dt, J=7.8, 1.4 Hz, 1H), 7.09 (dd, J=2.6, 1.6 Hz, 1H), 6.97-6.91 (m, 2H), 5.32 (s, 1H), 1.41-1.32 (m, 1H), 1.20-1.10 (m, 1H), 0.96-0.87 (m, 1H), 0.51-0.42 (m, 1H). HRMS (ESI): 350.1384 [M+H].sup.+.
Example 116 (S, E)-6-(3-(3-methoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one
[0198] Replace (E)-3-(o-methoxyphenyl)acrylic acid with (E)-3-(methoxyphenyl)acrylic acid, and replace oxazolin-2-one with (S)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-6-(3-(3-methoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one (yield 48.2%).1H NMR (500 MHz, Chloroform-d) 7.77 (d, J=15.0 Hz, 1H), 7.72-7.65 (m, 1H), 7.37-7.23 (m, 7H), 7.15 (t, J=1.5 Hz, 1H), 7.06 (ddt, J=7.5, 3.1, 1.6 Hz, 2H), 5.20 (d, J=0.7 Hz, 1H), 3.80 (s, 2H), 1.66-1.55 (m, 2H), 1.55-1.44 (m, 2H). LRMS (ESI): 350.15 [M+H].sup.+.
Example 117 (R, E)-6-(3-(3-phenoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one
[0199] Replace (E)-3-(o-methoxyphenyl)acrylic acid with (E)-3-(phenoxyphenyl)acrylic acid, and replace oxazolin-2-one with (R)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (R, E)-6-(3-(3-phenoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one (yield 51.1%). .sup.1H NMR (500 MHz, Chloroform-d) 7.91 (d, J=15.7 Hz, 1H), 7.72 (d, J=15.7 Hz, 1H), 7.42-7.30 (m, 9H), 7.24-7.21 (m, 1H), 7.13 (t, J=7.4 Hz, 1H), 7.04-6.99 (m, 3H), 5.31 (s, 1H), 1.39-1.32 (m, 1H), 1.19-1.11 (m, 1H), 0.96-0.88 (m, 1H), 0.52-0.42 (m, 1H). HRMS (ESI): 421.1542 [M+H].sup.+.
Example 118 (S, E)-6-(3-(3-phenoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one
[0200] Replace (E)-3-(o-methoxyphenyl)acrylic acid with (E)-3-(phenoxyphenyl)acrylic acid, and replace oxazolin-2-one with (S)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-6-(3-(3-phenoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one (yield 48.1%). .sup.1H NMR (500 MHz, Chloroform-d) 7.77 (d, J=15.0 Hz, 1H), 7.72-7.65 (m, 1H), 7.40-7.24 (m, 1OH), 7.20-7.15 (m, 1H), 7.18-7.00 (m, 6H), 5.19 (s, 1H), 1.66-1.44 (m, 5H). LRMS (ESI): 421.10 [M+H].sup.+.
Example 119 (R, E)-7-phenyl-6-(3-(2-(trifluoromethoxy)phenyl)acryloyl)-4-oxa-6-azaspiro [2.4]heptan-5-one
[0201] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(trifluoromethoxyphenyl)acrylic acid, and replace oxazolin-2-one with (R)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (R, E)-7-phenyl-6-(3-(2-(trifluoromethoxy)phenyl)acryloyl)-4-oxa-6-azaspiro [2.4]heptan-5-one (yield 34.2%). .sup.1H NMR (500 MHz, Chloroform-d) 8.08-7.96 (m, 2H), 7.80 (dd, J=7.8, 1.7 Hz, 1H), 7.45-7.24 (m, 8H), 5.32 (s, 1H), 1.41-1.32 (m, 1H), 1.19-1.12 (m, 1H), 0.97-0.90 (m, 1H), 0.51-0.43 (m, 1H). HRMS (ESI): 404.1105 [M+H].sup.+.
Example 120 (S, E)-7-phenyl-6-(3-(2-(trifluoromethoxy)phenyl)acryloyl)-4-oxa-6-azaspiro [2.4]heptan-5-one
[0202] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(trifluoromethoxyphenyl)acrylic acid, and replace oxazolin-2-one with (S)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-7-phenyl-6-(3-(2-(trifluoromethoxy)phenyl)acryloyl)-4-oxa-6-azaspiro [2.4]heptan-5-one (yield 36.5%). .sup.1H NMR (500 MHz, Chloroform-d) 7.81-7.75 (m, 1H), 7.63 (d, J=15.2 Hz, 1H), 7.56 (ddd, J=7.5, 1.5, 0.6 Hz, 1H), 7.38-7.26 (m, 6H), 7.23 (dd, J=7.5, 1.6 Hz, 1H), 6.99 (td, J=7.5, 1.6 Hz, 1H), 5.19 (s, 1H), 1.66-1.55 (m, 2H), 1.55-1.44 (m, 2H). LRMS (ESI): 404.13 [M+H].sup.+.
Example 121 (R, E)-6-(3-(4-methoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one
[0203] Replace (E)-3-(o-methoxyphenyl)acrylic acid with (E)-4-(methoxyphenyl)acrylic acid, and replace oxazolin-2-one with (R)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (R, E)-6-(3-(4-methoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one (yield 41.9%). .sup.1H NMR (600 MHz, Chloroform-d) 7.85-7.73 (m, 2H), 7.54 (d, J=8.5 Hz, 2H), 7.40-7.30 (m, 5H), 6.89 (d, J=8.6 Hz, 2H), 5.31 (s, 1H), 3.83 (s, 3H), 1.39-1.31 (m, 1H), 1.17-1.09 (m, 1H), 0.95-0.86 (m, 1H), 0.50-0.43 (m, 1H). LRMS (ESI): 350.40 [M+H].sup.+.
Example 122 (S, E)-6-(3-(4-methoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one
[0204] Replace (E)-3-(o-methoxyphenyl)acrylic acid with (E)-4-(methoxyphenyl)acrylic acid, and replace oxazolin-2-one with (S)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-6-(3-(4-methoxyphenyl)acryloyl)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one (yield 41.9%). .sup.1H NMR (600 MHz, Chloroform-d) 7.85-7.73 (m, 2H), 7.54 (d, J=8.5 Hz, 2H), 7.40-7.30 (m, 5H), 6.89 (d, J=8.6 Hz, 2H), 5.31 (s, 1H), 3.83 (s, 3H), 1.39-1.31 (m, 1H), 1.17-1.09 (m, 1H), 0.95-0.86 (m, 1H), 0.50-0.43 (m, 1H). LRMS (ESI): 350.40 [M+H].sup.+.
Example 123 (R, E)-6-(3-([1,1-biphenyl]-4-yl)acryloyl)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one
[0205] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-([1,1-biphenyl]-4-yl)acrylic acid, and replace oxazolin-2-one with (R)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (R, E)-6-(3-([1,1-biphenyl]-4-yl)acryloyl)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one (yield 33.2%). .sup.1H NMR (500 MHz, Chloroform-d) 7.97 (d, J=15.7 Hz, 1H), 7.80 (d, J=15.7 Hz, 1H), 7.68-7.56 (m, 6H), 7.47-7.28 (m, 8H), 5.30 (s, 1H), 1.39-1.31 (m, 1H), 1.18-1.09 (m, 1H), 0.96-0.87 (m, 1H), 0.50-0.42 (m, 1H). HRMS (ESI): 396.1599 [M+H].sup.+.
Example 124 (S, E)-6-(3-([1,1-biphenyl]-4-yl)acryloyl)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one
[0206] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-([1,1-biphenyl]-4-yl)acrylic acid, and replace oxazolin-2-one with (S)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-6-(3-([1,1-biphenyl]-4-yl)acryloyl)-7-phenyl-4-oxa-6-azaspiro [2.4]heptan-5-one (yield 33.2%). .sup.1H NMR (500 MHz, Chloroform-d) 7.97 (d, J=15.7 Hz, 1H), 7.80 (d, J=15.7 Hz, 1H), 7.68-7.56 (m, 6H), 7.47-7.28 (m, 8H), 5.30 (s, 1H), 1.39-1.31 (m, 1H), 1.18-1.09 (m, 1H), 0.96-0.87 (m, 1H), 0.50-0.42 (m, 1H). LRMS (ESI): 396.16 [M+H].sup.+.
Example 125 (S, E)-3-(3-(4-methoxyphenyl)acryloyl)-4-phenyloxazolidin-2-one
[0207] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-4-(methoxyphenyl)acrylic acid, and replace oxazolidin-2-one with (R)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-(4-methoxyphenyl)acryloyl)-4-phenyloxazolidin-2-one (yield 48.2%). .sup.1H NMR (600 MHz, Chloroform-d) 7.86-7.76 (m, 2H), 7.59-7.56 (m, 2H), 7.43-7.40 (m, 2H), 7.39-7.34 (m, 3H), 6.94-6.90 (m, 2H), 5.58 (dd, J=8.7, 3.9 Hz, 1H), 4.75 (t, J=8.8 Hz, 1H), 4.32 (dd, J=8.8, 3.9 Hz, 1H), 3.86 (s, 3H). HRMS (ESI): 324.1232 [M+H].sup.+.
Example 126 (S, E)-3-(3-(3-methoxyphenyl)acryloyl)-4-phenyloxazolidin-2-one
[0208] Replace (E)-3-(o-methylphenyl)acrylic acid with (E)-3-(methoxyphenyl)acrylic acid, and replace oxazolidin-2-one with (R)-4-phenyloxazolidin-2-one. The remaining required raw materials, reagents, and preparation methods were the same as in Example 1 to obtain (S, E)-3-(3-(3-methoxyphenyl)acryloyl)-4-phenyloxazolidin-2-one (yield 46.2%). .sup.1H NMR (600 MHz, Chloroform-d) 7.95 (d, J=15.7 Hz, 1H), 7.77 (d, J=15.7 Hz, 1H), 7.46-7.29 (m, 6H), 7.21 (d, J=7.6 Hz, 1H), 7.12 (s, 1H), 6.96 (d, J=8.2 Hz, 1H), 5.56 (d, J=8.5 Hz, 1H), 4.73 (t, J=8.8 Hz, 1H), 4.31 (d, J=8.8 Hz, 1H), 3.84 (s, 3H). HRMS (ESI): 324.1233 [M+H].sup.+.
Example of Pharmacological Activity Test
Example 1: Activity Determination of the Compound of the Present Invention for Improving Blood Flow
[0209] We used a laser speckle test blood flow model to test the activity of compounds in improving cerebral blood flow in mice. The principle is to measure the intensity changes of flowing blood through laser speckle technology, reflecting real-time cerebral blood flow; By comparing the changes in blood flow before and after administration in mice, the effect of compounds on improving blood flow can be detected.
[0210] The experimental process is shown in
[0211] Through the laser speckle model mentioned above, we conducted preliminary tests on the activity of the compound in improving cerebral blood flow in mice. In this experiment, ferulic acid (FA) was used as a positive control. The blood flow improvement effect of the compound is shown in
Example 2 Determination of Pharmacokinetic Parameters in the Compound of the Present Invention
[0212] Male ICR (CD-1) mice were divided into two groups, with three mice in each group. Each group was orally administered 20 mg/kg of the test substance or intravenously injected with 5 mg/kg of the test substance, blood was collected before administration, and 0.25 h, 0.5 h, 1 h, 2 h, 4 h, 8 h, and 24 hours after administration, respectively, and centrifuged immediately to obtain plasma, and the drug concentration in the plasma was determined using liquid chromatography tandem mass spectrometry.
[0213] The pharmacokinetic parameters in mice were shown in the following table. In mice, the oral bioavailability of compounds 27 and 83 was 14.7% and 17.4%, respectively, indicating good pharmacokinetic properties.
TABLE-US-00001 TABLE 2 Pharmacokinetic parameters of compounds 27 and 83 in mice Drug T.sub.max C.sub.max AUC.sub.0-t AUC.sub.0- MRT.sub.0- t.sub.1/2 CL F No. administration (h) (ng/mL) (ng .Math. h/mL) (ng .Math. h/mL) (h) (h) (mL/min/kg) (%) 27 po-20 mg/kg 1 104 465 650 6.12 4.01 / 14.7 iv-5 mg/kg / / 790 805 1.04 2.08 104 / 83 po-10 mg/kg 1 116 757 767 5.61 4.08 / 17.4 iv-5 mg/kg / / 2170 2200 1.21 1.56 37.8 /
[0214] In addition, by measuring the drug of the compound in brain tissue, it was found that the compound has good blood-brain barrier permeability, as shown in Table 3. Compound 27 has good brain tissue drug distribution after oral administration in mice, with a B/P of approximately 0.7.
TABLE-US-00002 TABLE 3 Determination of drug concentration in brain tissue Heart Plasma Portal Vein Brain CSF Brain/ Dose Animal No. Time (h) (ng/mL) Plasma (ng/mL) (ng/g) (ng/mL) H. Plasma PO 13 15 min 41.9 320 29.4 1.63 0.7 20 mg/kg 14 117 375 75.4 8.37 0.65 15 52.7 418 47.9 1.40 0.91 mean 70.4 371.1 50.9 3.8 0.7 16 30 min 34.2 252 19.4 0.670 0.56 17 28.2 171 38.8 0.770 1.37 18 89.5 704 44.3 5.94 0.49 mean 61.9 373.1 43.7 3.2 0.7
[0215] All references mentioned in the present invention are cited as references in this application, as if each reference were cited separately. In addition, it should be understood that after reading the above teaching content of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope of the claims attached to this application.