Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([C:18]([F:21])([F:20])[F:19])[CH:12]=2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[NH2:28][C:29]1[S:30][CH:31]=[CH:32][N:33]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl.CN(C)C=O>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([C:18]([F:19])([F:21])[F:20])[CH:12]=2)[C:8]([NH:28][C:29]2[S:30][CH:31]=[CH:32][N:33]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: Nc1nccs1
Reactant: O=C(O)C(CC1CCCC1)c1ccc(F)c(C(F)(F)F)c1
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=C(Nc1nccs1)C(CC1CCCC1)c1ccc(F)c(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 84.4 %

Procedure:
A solution of 3-cyclopentyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-propionic acid (304 mg, 1.0 mmol) in methylene chloride (10 mL) was cooled to 0° C. and then treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.6 mL, 1.2 mmol) and a few drops of N,N-dimethylformamide. The reaction mixture was stirred at 0° C. for 15 min and at 25° C. for 24 h. The reaction mixture was then treated with 2-amino-thiazole (175 mg, 1.75 mmol) and N,N-diisopropylethylamine (0.4 mL, 2.41 mmol). This solution was stirred at 25° C. for 48 h. At this time, the reaction was concentrated in vacuo. High pressure liquid chromatography (Chromegasphere SI-60, 10 μM, 60 Å, 25 cm×23 cm ID, 60/40 heptane/ethyl acetate) afforded 3-cyclopentyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-N-thiazol-2-yl-propionamide (326 mg, 84.5%) as a light yellow solid: mp 125–127° C.; EI-HRMS m/e calcd for C18H18F4N2OS (M+) 386.1076, found 386.1086.
Reaction SMILES: C([O:5][N:6]=[C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH2:18][CH2:19][Cl:20])[CH:15]=2)[O:10][C:9]([C:21]2[N:26]=[CH:25][N:24]3[CH:27]=[CH:28][CH:29]=[C:23]3[CH:22]=2)=[CH:8]1)(C)(C)C.[F:30][C:31]1([F:36])[CH2:35][CH2:34][NH:33][CH2:32]1>>[ClH:20].[F:30][C:31]1([F:36])[CH2:35][CH2:34][N:33]([CH2:19][CH2:18][O:17][C:14]2[CH:15]=[C:16]3[C:11](=[CH:12][CH:13]=2)[O:10][C:9]([C:21]2[N:26]=[CH:25][N:24]4[CH:27]=[CH:28][CH:29]=[C:23]4[CH:22]=2)=[CH:8][C:7]3=[N:6][OH:5])[CH2:32]1
Reactant: CC(C)(C)ON=c1cc(-c2cc3cccn3cn2)oc2ccc(OCCCl)cc12
Reactant: FC1(F)CCNC1
Product: Cl
Product: ON=c1cc(-c2cc3cccn3cn2)oc2ccc(OCCN3CCC(F)(F)C3)cc12

Procedure:
6-[2-(3,3-difluoro-pyrrolidin-1-yl)-ethoxy]-2-pyrrolo[1,2-c]pyrimidin-3-yl-chromen-4-one oxime, hydrochloride was prepared in 42% overall yield using the method described in example 87, starting from 6-(2-chloro-ethoxy)-2-pyrrolo[1,2-c]pyrimidin-3-yl-chromen-4-one O-tert-butyl oxime (example 87B) and 3,3-difluoro-pyrrolidine.
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.O[CH2:12][C@H:13]1[CH2:18][O:17][CH2:16][C@@H:15]([C:19]2[CH:24]=[C:23]([F:25])[C:22]([F:26])=[C:21]([F:27])[CH:20]=2)[N:14]1C(OCC1C2C=CC=CC=2C2C1=CC=CC=2)=O.[Cl-].[NH4+].[C:47]([O:50][CH2:51]C)(=[O:49])[CH3:48]>ClCCl.C(N(CC)CC)C>[F:25][C:23]1[CH:24]=[C:19]([C@H:15]2[NH:14][C@@H:13]([CH:12]=[CH:48][C:47]([O:50][CH3:51])=[O:49])[CH2:18][O:17][CH2:16]2)[CH:20]=[C:21]([F:27])[C:22]=1[F:26]
Reactant: O=C(OCC1c2ccccc2-c2ccccc21)N1[C@@H](CO)COC[C@H]1c1cc(F)c(F)c(F)c1
Reactant: CCOC(C)=O
Agent: O=C(Cl)C(=O)Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: CS(C)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)C=C[C@H]1COC[C@@H](c2cc(F)c(F)c(F)c2)N1
Temperature: -78 °C
Reaction time: 0.08 h

Procedure:
DMSO (0.14 mL) was added to a solution of oxalyl chloride (0.16 mL) in dichloromethane (10 mL) in a nitrogen atmosphere at −78° C. over five minutes, and the reaction solution was stirred at −78° C. for five minutes. A solution of 9H-fluoren-9-ylmethyl (3S,5R)-3-hydroxymethyl-5-(3,4,5-trifluorophenyl)morpholine-4-carboxylate (470 mg) in dichloromethane (2 mL) was added to the reaction solution at −78° C., and the reaction solution was stirred at −78° C. for 30 minutes. Triethylamine (0.86 mL) was added to the reaction solution at −78° C., and the reaction solution was stirred at −78° C. for 20 minutes. A saturated ammonium chloride solution was added to the reaction solution at −78° C., and the reaction solution was heated to room temperature. Then, dichloromethane was added to the reaction solution, and the organic layer was separated. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. Trimethyl phosphonoacetate (0.28 mL) was added to a mixed solution of sodium hydride (containing 60% mineral oil, 58 mg) in THF (10 mL)-DMF (2 mL) at 0° C., and the reaction solution was stirred at 0° C. for 30 minutes. A solution of the residue obtained above in THF (2 ml) was added to the reaction solution at 0° C., and the reaction solution was stirred at 0° C. for 30 minutes. A saturated ammonium chloride solution and ethyl acetate were added to the reaction solution, and the organic layer was separated. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. Diethylamine (1 mL) was added to a solution of the residue in acetonitrile (4 mL), and the reaction solution was stirred for 30 minutes. Toluene was added to the reaction solution, which was then concentrated under reduced pressure. The residue was purified by silica gel chromatography (elution solvent: heptane->heptane:ethyl acetate=1:1) to obtain 227 mg of an E/Z isomer mixture of the title compound. The property values of the compound are as follows.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([SH:22])[NH:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[CH:5][CH:4]=1.[H-].[Na+].Cl.Cl[C:27]1[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=1>CN(C)C=O>[CH3:21][O:20][C:17]1[CH:18]=[CH:19][C:14]([C:13]2[N:12]=[C:11]([S:22][C:27]3[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=3)[NH:10][C:9]=2[C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)=[CH:15][CH:16]=1
Reactant: COc1ccc(-c2nc(S)[nH]c2-c2ccc(OC)cc2)cc1
Reactant: Clc1ccncc1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(-c2nc(Sc3ccncc3)[nH]c2-c2ccc(OC)cc2)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 82 %

Procedure:
3.12 g of 4,5-bis(4-methoxyphenyl)-2-mercaptoimidazole is dissolved in 100 ml of absolute dimethylformamide and combined with 0.6 g of sodium hydride (80% strength in white oil). The mixture is further agitated for 30 minutes, and then 1.52 g of 4-chloropyridine hydrochloride is added. The mixture is refluxed under argon for 16 hours. Then the solution is poured into 300 ml of ice water, the product is extracted with ethyl acetate, the organic solution is dried over sodium sulfate and concentrated to dryness under vacuum. The residue is recrystallized from acetone/ether, thus obtaining 3.19 g of 4,5-bis(4-methoxyphenyl)-2-(4-pyridylthio)imidazole, mp 177°-179°.
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[CH2:11]([Br:14])[C:12]#[CH:13]>>[Br-:14].[CH3:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N+:6]=1[CH2:13][C:12]#[CH:11]
Reactant: Cc1nc2ccccc2s1
Reactant: C#CCBr
Product: C#CC[n+]1c(C)sc2ccccc21
Product: [Br-]
Yield: 69.1 %

Procedure:
14.9 g of 2-methylbenzothiazole and 12.5 g of propargyl bromide were heated at 80 to 100° C on a hot water bath for 3 hours. The precipitated crystals were washed with acetone to obtain 18.5 g of 2-methyl-3-propargylbenzothiazolium bromide, m.p. 214°- 215° C.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH:15]1[C:25]2[CH:24]=[CH:23][C:22]3[CH:26]=[CH:27][CH:28]=[CH:29][C:21]=3[CH:20]([C:30]3[C:31](=[O:37])[NH:32][C:33](=[O:36])[NH:34][CH:35]=3)[C:19]=2[CH:18]=[CH:17][CH:16]=1>CS(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([N:34]2[CH:35]=[C:30]([CH:20]3[C:19]4[CH:18]=[CH:17][CH:16]=[CH:15][C:25]=4[CH:24]=[CH:23][C:22]4[CH:26]=[CH:27][CH:28]=[CH:29][C:21]3=4)[C:31](=[O:37])[NH:32][C:33]2=[O:36])[CH:5]=[CH:4][N:3]=1
Reactant: Clc1ccnc(Cl)n1
Reactant: O=c1[nH]cc(C2c3ccccc3C=Cc3ccccc32)c(=O)[nH]1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CS(C)=O
Product: O=c1[nH]c(=O)n(-c2ccnc(Cl)n2)cc1C1c2ccccc2C=Cc2ccccc21

Procedure:
A mixture of 2,4-dichloropyrimidine (1.49 g), cesium carbonate (3.26 g) and the product of example 1 step (iv) (3 g) in dimethylsulphoxide (40 ml) was stirred at room temperature for 3 hours and partitioned between ethyl acetate and water. The organic phase was dried (MgSO4) and evaporated. The product was collected after trituration with 50% ethyl acetate in isohexane. Yield 2.55 g.
Reaction SMILES: [NH2:1][C:2]1[CH:13]=[CH:12][CH:11]=[CH:10][C:3]=1[C:4]([N:6]([CH2:8][CH3:9])[CH3:7])=[O:5].[CH2:14]([NH:16][CH3:17])[CH3:15].C12C(=CC=CC=1)[NH:23][C:22](=O)OC2=O>>[NH:16]1[CH2:17][CH2:22][N:23]=[C:14]1[CH2:15][NH:1][C:2]1[CH:13]=[CH:12][CH:11]=[CH:10][C:3]=1[C:4]([N:6]([CH2:8][CH3:9])[CH3:7])=[O:5]
Reactant: O=c1[nH]c2ccccc2c(=O)o1
Reactant: CCNC
Reactant: CCN(C)C(=O)c1ccccc1N
Product: CCN(C)C(=O)c1ccccc1NCC1=NCCN1

Procedure:
2-Amino-N-ethyl-N-methylbenzamide (prepared from N-ethylmethylamine and isatoic anhydride, using the methods described in Example 17) and CMI were reacted using conditions described in the general procedure for CMI coupling to give 2-[(4,5-dihydro-1H-imidazol-2-ylmethyl)amino]-N-ethyl-N-methylbenzamide.
Reaction SMILES: [CH2:1]([P:3]([O-:9])[O:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH3:2].[CH:10](=[O:13])[CH:11]=[CH2:12].[O-]CCCC.[Na+]>>[CH2:1]([P:3]([CH2:12][CH2:11][CH:10]=[O:13])(=[O:9])[O:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH3:2]
Reactant: C=CC=O
Reactant: CCCCOP([O-])CC
Agent: CCCC[O-]
Agent: [Na+]
Product: CCCCOP(=O)(CC)CCC=O
Yield: 88.9 %

Procedure:
A 1 l five-neck flask equipped with thermometer, reflux condenser, high-performance stirrer and dropping funnel was initially charged with 447 g (3 mol) of butyl ethylphosphonite (produced as in Example 3) and 168 g (3 mol) of 2-propenal. While stirring, 15 ml of sodium butoxide (30% strength in butanol) are added dropwise at such a rate that a reaction temperature of max. 120° C. becomes established. The crude product thus obtained is distilled in vacuo to obtain 550 g (89% of theory) of butyl ethyl-(2-formylethyl)phosphinate as colorless liquid.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16](=[O:33])[NH:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20](B2OC(C)(C)C(C)(C)O2)[CH:19]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:35]1[CH:36]=[C:37]([CH:40]=[CH:41][CH:42]=1)[C:38]#[N:39].CN(C=O)C>CO.C([O-])(O)=O.[Na+]>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16](=[O:33])[NH:17][C:18]1[CH:19]=[C:20]([C:35]2[CH:42]=[CH:41][CH:40]=[C:37]([C:38]#[N:39])[CH:36]=2)[CH:21]=[CH:22][CH:23]=1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC1(C)OB(c2cccc(NC(=O)[C@@H]3CCCN3C(=O)OCc3ccccc3)c2)OC1(C)C
Reactant: N#Cc1cccc(Br)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: CN(C)C=O
Product: N#Cc1cccc(-c2cccc(NC(=O)[C@@H]3CCCN3C(=O)OCc3ccccc3)c2)c1
Temperature: 70 °C

Procedure:
A solution of (S)-2-[3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylcarbamoyl]-pyrrolidine-1-carboxylic acid benzyl ester (90.4 mg, 0.20 mmol), 3-bromo-benzonitrile (37.5 mg, 0.21 mmol), and Pd[P(Ph)3]4 (15.9 mg, 6.9 mol %) in methanol (2 mL), NaHCO3 (sat. aq., 300 μL), and DMF (400 μL) was degassed and heated to 70° C. overnight in a sealed vial. The reaction was cooled, filtered, and purified by reverse phase HPLC to give the desired product. Yield 11.7 mg. MS: 426.1 (M+H+); H1 NMR (DMSO-d6): δ (ppm) 1.80-2.04 (m, 3H), 2.15-2.36 (m, 1H), 3.39-3.58 (m 2H), 4.32-4.43 (m, 1H), 4.89-5.14 (m, 2H), 7.03-8.07 (m, 13H), 10.13-10.20 (s, 1H).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]#[N:11])[CH:5]=[CH:6][CH:7]=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.[CH3:26][C:27]1[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[C:28]=1[CH2:29]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[CH3:26][C:27]1[CH:34]=[CH:33][CH:32]=[C:31]([CH3:35])[C:28]=1[CH2:29][O:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]#[N:11])[CH:5]=[CH:6][CH:7]=1
Reactant: N#CCCc1cccc(O)c1
Reactant: Cc1cccc(C)c1CO
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Cc1cccc(C)c1COc1cccc(CCC#N)c1
Temperature: 25 °C

Procedure:
A solution of 3-(3-hydroxyphenyl)propanenitrile (Step B, 1.25 g, 8.5 mmol) and diisopropyl azodicarboxylate (DIAD, 1.87 g, 9.26 mmol) in dry THF (10 ml) was added drop wise to a solution of 2,6-Dimethylbenzyl alcohol (1.27 g, 9.3 mmol) and triphenylphosphine (TPP, 2.43 g, 9.26 mmol) in dry THF (30 ml) at 0° C. under argon. The reaction mixture was warmed to room temperature for 4 hours or until all the starting material is consumed diluted with ether and washed with water (2×). The organic layer was dried over Na2SO4, filtered, concentrated, and purified by flash chromatography on a silica gel column (hex:ethyl acetate 2:1) to give the title compound.
Reaction SMILES: [C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1[CH:13]=[C:12](Cl)[C:11]([Cl:15])=[CH:10][C:9]=1[N+:16]([O-:18])=[O:17])([CH3:4])([CH3:3])[CH3:2].[NH:20]1[CH2:23][CH2:22][CH2:21]1.CCN(CC)CC>CS(C)=O>[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1[CH:13]=[C:12]([N:20]2[CH2:23][CH2:22][CH2:21]2)[C:11]([Cl:15])=[CH:10][C:9]=1[N+:16]([O-:18])=[O:17])([CH3:4])([CH3:3])[CH3:2]
Reactant: C1CNC1
Reactant: CC(C)(C)OC(=O)Nc1cc(Cl)c(Cl)cc1[N+](=O)[O-]
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: CC(C)(C)OC(=O)Nc1cc(N2CCC2)c(Cl)cc1[N+](=O)[O-]

Procedure:
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (6.14 g, 20 mmol), azetidine (2.33 mL, 34 mmol) and Et3N (8.4 mL, 60 mmol) in DMSO (40 mL) at 23° C. according to the general procedure C. Obtained as an orange solid (5.85 g).
Reaction SMILES: [O-:1][Mn](=O)(=O)=O.[K+].[C:7]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:12]=[CH:11][C:10]([C:13]2[C:23]([F:24])=[CH:22][C:16]3[NH:17][C:18]([S:20][CH3:21])=[N:19][C:15]=3[CH:14]=2)=[CH:9][CH:8]=1.[OH2:31]>C(O)(=O)C.CCOC(C)=O>[C:7]1([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:12]=[CH:11][C:10]([C:13]2[C:23]([F:24])=[CH:22][C:16]3[NH:17][C:18]([S:20]([CH3:21])(=[O:1])=[O:31])=[N:19][C:15]=3[CH:14]=2)=[CH:9][CH:8]=1
Reactant: O
Reactant: CSc1nc2cc(-c3ccc(-c4ccccc4)cc3)c(F)cc2[nH]1
Reactant: O=[Mn](=O)(=O)[O-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CS(=O)(=O)c1nc2cc(-c3ccc(-c4ccccc4)cc3)c(F)cc2[nH]1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To 32 mL of acetic acid was added compound 13-5 (2.34, 6.4 mmol) resulting in a suspension. In a separate flask KMnO4 (2.48 g, 15.7 mmol) was dissolved in 40 mL of H2O. The KMnO4 solution was then added to the solution of compound 13-5 in acetic acid and allowed to stir for 2 h at ambient temperature. The dark reaction mixture was diluted with EtOAc (200 mL) and washed three times with 150 mL portions of brine. The combined organic layers were dried over MgSO4, then filtered and concentrated in vacuo to give title compound 13-6 as a pale yellow solid.
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[CH2:6]([N:8]([CH2:31][CH3:32])[C:9]([NH:11][C@H:12]1[CH2:26][C@H:25]2[C@@H:15]([CH2:16][C:17]3[C:27]4[C:20](=[CH:21][C:22]([CH3:28])=[CH:23][C:24]2=4)[NH:19][C:18]=3[CH3:29])[N:14]([CH3:30])[CH2:13]1)=O)[CH3:7].CCOC([S-])=[S:37].[K+].N>ClCCl.C(#N)C>[CH2:6]([N:8]([CH2:31][CH3:32])[C:9]([NH:11][C@H:12]1[CH2:26][C@H:25]2[C@@H:15]([CH2:16][C:17]3[C:27]4[C:20](=[CH:21][C:22]([CH3:28])=[CH:23][C:24]2=4)[NH:19][C:18]=3[CH3:29])[N:14]([CH3:30])[CH2:13]1)=[S:37])[CH3:7]
Reactant: CCOC(=S)[S-]
Reactant: CCN(CC)C(=O)N[C@H]1C[C@@H]2c3cc(C)cc4[nH]c(C)c(c34)C[C@H]2N(C)C1
Agent: N
Agent: [K+]
Solvent: ClCCl
Solvent: O=P(Cl)(Cl)Cl
Solvent: CC#N
Product: CCN(CC)C(=S)N[C@H]1C[C@@H]2c3cc(C)cc4[nH]c(C)c(c34)C[C@H]2N(C)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 43 %

Procedure:
0.5 M1 of freshly distilled phosphorus oxychloride (5.6 mmol) and 368 mg of 1,1-diethyl-3-(2,6,13-trimethyl-8alpha- ergolinyl)-urea (1 mmol) are dissolved in 20 ml of dichloromethane at -20° C. and the mixture is allowed to stir overnight at room temperature. The volatile portions are now drawn off in a vacuum, the residue is dissolved in 40 ml of acetonitrile and mixed with a solution of 0.8 g of potassium xanthate (5.6 mmol) in 80 ml of acetonitrile. It is stirred for 2 hours at room temperature, then ice and conc. ammonia solution are added and shaken out with dichloromethane. The organic phases are dried with sodium sulfate and concentrated by evaporation, the residue is chromatographed on silica gel with ethyl acetate and crystallized from ethyl acetate/diisopropyl ether, yield 43%.
Reaction SMILES: [F:1][C:2]1[CH:40]=[CH:39][C:5]([C:6]([NH:8][C@:9]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[C:33]([OH:38])[CH:32]=2)([C:17]2[CH:22]=[C:21]([O:23][C:24]([F:29])([F:28])[CH:25]([F:27])[F:26])[CH:20]=[C:19]([F:30])[CH:18]=2)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:7])=[CH:4][C:3]=1[C:41]([F:44])([F:43])[F:42].C([O-])([O-])=O.[Na+].[Na+].[C:51](OC=C)(=O)[CH3:52]>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:40]=[CH:39][C:5]([C:6]([NH:8][C@:9]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[C:33]([O:38][CH:51]=[CH2:52])[CH:32]=2)([C:17]2[CH:22]=[C:21]([O:23][C:24]([F:28])([F:29])[CH:25]([F:27])[F:26])[CH:20]=[C:19]([F:30])[CH:18]=2)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:7])=[CH:4][C:3]=1[C:41]([F:44])([F:43])[F:42]
Reactant: O=C(N[C@@](Cc1ccccc1)(c1cc(F)cc(OC(F)(F)C(F)F)c1)c1ccc(F)c(O)c1)c1ccc(F)c(C(F)(F)F)c1
Reactant: C=COC(C)=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: C=COc1cc([C@@](Cc2ccccc2)(NC(=O)c2ccc(F)c(C(F)(F)F)c2)c2cc(F)cc(OC(F)(F)C(F)F)c2)ccc1F
Temperature: 100 °C
Reaction time: 16 h

Procedure:
To a solution of (R)-4-fluoro-N-(1-(4-fluoro-3-hydroxyphenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3-(trifluoromethyl)benzamide (Example 264, 100 mg, 0.158 mmol) in toluene (0.2 ml) was added Na2CO3 (25 mg, 0.235 mmol) and catalystical amount of [Ir(cod)Cl]2 (2 mg), followed by vinyl acetate (68 mg, 0.79 mmol). The reaction mixture was stirred at 100° C. for 16 h. The resulting mixture was filtered and the solid was washed with CH2Cl2. The CH2Cl2 layer was washed with 1 N NaOH, H2O and dried over Na2SO4 and filtered. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column using 0 to 60% EtOAc in hexane to afford (R)-4-fluoro-N-(1-(4-fluoro-3-(vinyloxy)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-3-(trifluoromethyl)benzamide eluting out at 20% EtOAc in hexane as colorless oil (80 mg, 77%). LCMS: RT=2.237 min [M+H] 658.3 (2 min Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm. NMR: 400 MHz 1H (CD3OD) ppm 3.87 (d, J=12.74 Hz, 1H), 4.05-4.15 (m, 1H), 4.35 (dd, J=5.93, 1.98 Hz, 1H), 4.55 (dd, J=13.84, 1.98 Hz, 1H), 6.12-6.41 (m, 1H), 6.48 (dd, J=13.62, 6.15 Hz, 1H), 6.72 (d, J=7.03 Hz, 2H), 6.87-7.24 (m, 9H), 7.37-7.51 (m, 1H), 7.88-8.04 (m, 2H).
Reaction SMILES: [OH:1][C:2]1[CH:23]=[CH:22][C:5]2[CH:6]=[C:7]([C:9](=O)[CH2:10][C:11](=O)/[CH:12]=[CH:13]/[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[O:8][C:4]=2[CH:3]=1.O.[NH2:25][NH2:26]>C(O)(=O)C.C(O)C>[C:14]1(/[CH:13]=[CH:12]/[C:11]2[NH:26][N:25]=[C:9]([C:7]3[O:8][C:4]4[CH:3]=[C:2]([OH:1])[CH:23]=[CH:22][C:5]=4[CH:6]=3)[CH:10]=2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: NN
Reactant: O=C(/C=C/c1ccccc1)CC(=O)c1cc2ccc(O)cc2o1
Solvent: CC(=O)O
Solvent: CCO
Solvent: O
Product: Oc1ccc2cc(-c3cc(/C=C/c4ccccc4)[nH]n3)oc2c1
Temperature: 382.5 °C
Yield: 11 %

Procedure:
To a mixture of (4E)-1-(6-hydroxy-1-benzofuran-2-yl)-5-phenylpent-4-ene-1,3-dione (0.48 mmol) and hydrazine monohydrate (0.02 g, 0.48 mmol) were added ethanol (24 mL) and acetic acid (1 drop) in a sealed tube. The reaction was heated at 65-700° C. overnight. The solvent was removed under reduced pressure to afford crude product. The crude product was purified by reverse phase HPLC. The fractions from HPLC were combined, neutralized with 1.0 N aqueous sodium hydroxide solution, and diluted with ethyl acetate (200 mL). The organic layer was washed with saturated aqueous sodium chloride (50 mL), dried over magnesium sulfate, filtered, and concentrated to afford the product (11% yield): 1H NMR (400 MHz, CD3Cl): δ 7.58 (br d, 2H), 7.35 (m, 4H), 7.25 (t, 2H), 7.10 (br d, 1H), 7.05 (br s, 1H), 6.94 (br d, 1H), 6.88 (br s, 1H), 6.75 (dd, 1H); MS (EI) for C19H14N2O2: 303 (MH+).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][OH:5].[C:10]([O-])([O-])=O.[K+].[K+].[CH2:16](O)[CH3:17]>>[CH:16]([O:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][OH:5])([CH3:17])[CH3:10]
Reactant: OCc1ccccc1O
Reactant: O=C([O-])[O-]
Reactant: CCO
Agent: [K+]
Product: CC(C)Oc1ccccc1CO
Yield: 99 %

Procedure:
A mixture of 2-hydroxybenzyl alcohol (21.04 g, 1 equiv., available from Aldrich Chemical Company), 2-isopropyl iodide (32.3 mL, 1.9 equiv., available from Aldrich Chemical Company) and K2CO3 (71.42 g, 3 equiv.) in ethanol was refluxed for 3 hours. On cooling the reaction mixture was filtered and the solvent removed under reduced pressure and replaced with dichloromethane, and then filtered and the solvent removed to give the title compound as an oil (27.751 g, 99%). 1H NMR (300 MHz, CDCl3): δ 1.37 (d, 6H, J=6.0 Hz), 3.55 (bs, 1H), 4.50-4.70 (m, 3H), 6.78-6.90 (m, 2H), 7.15-7.25 (m, 2H).
Reaction SMILES: [C:1]([NH:4][CH2:5][C@@H:6]1[O:10][C:9](=[O:11])[N:8]([C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[C:14]([F:19])[CH:13]=2)[CH2:7]1)(=O)[CH3:2].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:29])=CC=1>O1CCOCC1>[C:1]([NH:4][CH2:5][C@@H:6]1[O:10][C:9](=[O:11])[N:8]([C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[C:14]([F:19])[CH:13]=2)[CH2:7]1)(=[S:29])[CH3:2]
Reactant: CC(=O)NC[C@H]1CN(c2ccc(N)c(F)c2)C(=O)O1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: C1COCCO1
Product: CC(=S)NC[C@H]1CN(c2ccc(N)c(F)c2)C(=O)O1
Yield: 98 %

Procedure:
A mixture of 5-(S)-acetamidomethyl-3-[4′-amino-3′-fluorophenyl]oxazolidine-2-one. (0.100 g, 0.374 mmol) and Lawesson's reagent (0.151 g, 0.374 mol) in dioxane (2 ml) was stirred at 65° C. for 2 h. The solution was concentrated under vacuum and the residue purified by PTLC (10% methanol/dichloromethane) to give a tan solid (0.104 g, 98%); mp 137-88° C.; MS: (M+H)+=284.
Reaction SMILES: [C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[O:12](C1C=C(C=CC=1)N)C1C=CC(N)=CC=1.NC1C=C(C=CC=1)OC1C=CC=C(OC2C=CC=C(N)C=2)C=1.C1(=O)OC(=O)C2=CC=CC=C12>CN1CCCC1=O>[CH:8]1[CH:7]=[C:3]([C:4]([NH2:5])=[O:6])[C:2]([C:1]([OH:11])=[O:12])=[CH:10][CH:9]=1
Reactant: Nc1ccc(Oc2cccc(N)c2)cc1
Reactant: O=C1NC(=O)c2ccccc21
Agent: Nc1cccc(Oc2cccc(Oc3cccc(N)c3)c2)c1
Agent: O=C1OC(=O)c2ccccc21
Solvent: CN1CCCC1=O
Product: NC(=O)c1ccccc1C(=O)O
Temperature: 25 °C
Reaction time: 16 h

Procedure:
The following example illustrates the synthesis of a phthalimide-terminated imide oligomer with theoretical number average molecular weight of 11,600 g/mole. 3,4'-Oxydianiline (ODA) (63.75 mmole, 12.7653 g) and 1,3-bis(3-aminophenoxy)benzene (APB) (11.25 mmole, 3.2888 g) were dissolved in N-methylpyrrolidinone (NMP) (~50 mL) in a flask equipped with a mechanical stirrer, condenser and nitrogen inlet. 3,3',4,4'-Biphenyl tetracarboxylic dianhydride (BPDA) (72.0 mmole, 21.1838 g) and phthalic anhydride (PA) (6.0 mmole, 0.8888 g) were slurried in NMP (~50 mL) and were added to the solution. After washing with ~32 mL of NMP to provide a 20% solids content reaction, an exotherm of 10-15° C. was observed. The exotherm quickly subsided and the reaction was stirred at 25° C. for 16 h to form the phthalamide acid-terminated polyamide acid. The inherent viscosity (ηinh)) of the phthalamide acid-terminated polyamide acid was 0.47 dL/g in NMP at 25° C. To imidize, toluene (30 mL) was added and the reaction was heated at 160° C. for 24 h. After cooling, a powder precipitated which was washed twice in water and dried ~230° C. in a vacuum to afford a yellow solid in high yield. The resulting phthalimide-terminated polyimide was insoluble in NMP and had a glass transition temperature 245° C. and a melting point at ~357° C. A film cast from the polyamide acid solution and dried 1 hour each at 100, 225, and 371° C. had a Tg of 248° C. and a Tm at 357° C. and was tough and creasible.