Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:40])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[C:31]([F:33])[C:30]([NH2:34])=[CH:29][C:28]=3[O:35][C:36]([F:39])([F:38])[F:37])=[CH:23][CH:22]=2)[N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].C(Cl)Cl.[F:44][C:45]1[CH:50]=[CH:49][C:48]([C:51](Cl)=[O:52])=[CH:47][N:46]=1>>[CH3:1][O:2][C:3](=[O:40])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[C:31]([F:33])[C:30]([NH:34][C:51]([C:48]4[CH:47]=[N:46][C:45]([F:44])=[CH:50][CH:49]=4)=[O:52])=[CH:29][C:28]=3[O:35][C:36]([F:38])([F:39])[F:37])=[CH:23][CH:22]=2)[N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]
Reactant: COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1nc(-c2ccc(-c3cc(F)c(N)cc3OC(F)(F)F)cc2)c[nH]1)C(C)C
Reactant: O=C(Cl)c1ccc(F)nc1
Solvent: ClCCl
Product: COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1nc(-c2ccc(-c3cc(F)c(NC(=O)c4ccc(F)nc4)cc3OC(F)(F)F)cc2)c[nH]1)C(C)C
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
To a solution of ((S)-1-{(S)-2-[4-(4′-amino-5′-fluoro-2′-trifluoromethoxy-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (50 mg, 0.09 mmol, Preparation 43) in DCM (0.6 mL, 9 mmol) was slowly added 2-fluoropyridine-5-carbonyl chloride (10 mg, 0.09 mmol;) and the reaction mixture was stirred at room temperature for 5 min and then concentrated to provide a colored solid.
Reaction SMILES: [CH3:1][C:2]1([CH3:22])[CH:6]([C:7]2[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=2)[C:5]2[C:14]([CH3:21])=[C:15]([NH2:20])[C:16]([CH3:19])=[C:17]([CH3:18])[C:4]=2[O:3]1.[C:23]1([CH:29]2[CH2:34][C:33](=O)[O:32][C:30]2=[O:31])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C([O-])(=O)C.[Na+]>C1(C)C=CC=CC=1.C(OC(=O)C)(=O)C>[CH3:1][C:2]1([CH3:22])[CH:6]([C:7]2[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][CH:12]=2)[C:5]2[C:14]([CH3:21])=[C:15]([N:20]3[C:33](=[O:32])[CH2:34][CH:29]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C:30]3=[O:31])[C:16]([CH3:19])=[C:17]([CH3:18])[C:4]=2[O:3]1
Reactant: O=C1CC(c2ccccc2)C(=O)O1
Reactant: Cc1ccc(C2c3c(C)c(N)c(C)c(C)c3OC2(C)C)cc1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CC(=O)OC(C)=O
Product: Cc1ccc(C2c3c(C)c(N4C(=O)CC(c5ccccc5)C4=O)c(C)c(C)c3OC2(C)C)cc1
Temperature: 90 °C
Reaction time: 1 h
Yield: 50 %

Procedure:
A solution of 2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-amine (2.95 g, 10 mmol) and phenylsuccinic anhydride (1.94 g, 11 mmol) in toluene was refluxed for 6 hours. The reaction mixture was concentrated under reduced pressure. The residue was diluted with water and extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. A mixture of the residue and sodium acetate (0.86 g, 10.5 mmol) in acetic anhydride (60 ml) was stirred at 90° C. for 1 hour. The reaction mixture was concentrated under reduced pressure. The residue was diluted with water and extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and removed under reduced pressure. The residue was purified with silica gel column chromatography (hexane/ethyl acetate−4/1) to obtain 2.27 g (yield 50%) of the title compound. mp. 130–131° C. low polarity product, 1H-NMR (CDCl3) δ: 1.00 (3H, s)=1.52 (3H, s), 1.64 (3H, s), 2.02 (3H, s), 2.16 (3H, s), 2.30 (3H, s), 3.00 (1H, dd, J=4.7, 18.5 Hz), 3.36 (1H, dd, J=9.5, 18.5 Hz), 4.15–4.25 (2H, m), 6.85 (2H, br), 7.06 (2H, brd, J=6.6 Hz), 7.30–7.47 (5H, m).
Reaction SMILES: [OH:1][CH:2]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:3][CH2:4][CH:5]1[CH2:9][CH2:8][C:7](=[O:10])[N:6]1[CH2:11][CH2:12][CH2:13][C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=1.[N:29]([Si](C)(C)C)=[N+:30]=[N-:31].C([Sn](=O)CCCC)CCC>C1(C)C=CC=CC=1>[OH:1][CH:2]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:3][CH2:4][CH:5]1[N:6]([CH2:11][CH2:12][CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:18]3[N:29]=[N:30][NH:31][N:19]=3)=[CH:20][CH:21]=2)[C:7](=[O:10])[CH2:8][CH2:9]1
Reactant: N#Cc1ccc(CCCN2C(=O)CCC2CCC(O)Cc2ccccc2)cc1
Reactant: C[Si](C)(C)N=[N+]=[N-]
Agent: CCCC[Sn](=O)CCCC
Solvent: Cc1ccccc1
Product: O=C1CCC(CCC(O)Cc2ccccc2)N1CCCc1ccc(-c2nn[nH]n2)cc1
Yield: 82.3 %

Procedure:
Analogous to the procedure described for Example 4A, Step E, 4-{3-[2-(3-hydroxy-4-phenyl-butyl)-5-oxo-pyrrolidin-1-yl]-propyl}-benzonitrile (157.8 mg, 0.419 mmol) was reacted with azidotrimethylsilane (0.11 mL, 0.84 mmol) and dibutyltin oxide (20 mg, 0.08 mmol) in toluene (8.6 mL) heated under reflux for 60 h. Purification by medium pressure chromatography (CH2Cl2 to 2% MeOH in CH2Cl2 to 4% MeOH in CH2Cl2 to 6% MeOH in CH2Cl2) provided 5-(3-hydroxy-4-phenyl-butyl)-1-{3-[4-(2H-tetrazol-5-yl)-phenyl]-propyl}-pyrrolidin-2-one (144.7 mg). 1H NMR (CDCl3) δ8.02 (m, 2H), 7.27 (m, 7H), 3.84 (m, 1H), 3.67 (m, 2H), 3.10 (m, 1H), 2.84 (m, 1H), 2.67 (m, 2H), 2.53 (m, 1H), 2.42 (m, 1H), 2.14 (m, 1H), 1.97–1.40 (m, 9H); MS 420.3 (M+1), 418.3 (M−1).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[CH2:4][C@H:5]1[C:9]2[CH:10]=[CH:11][C:12]([OH:14])=[CH:13][C:8]=2[O:7][CH2:6]1.[CH2:16]([C:18]1[CH:23]=[C:22]([O:24][CH2:25][CH2:26][CH2:27][S:28]([CH3:31])(=[O:30])=[O:29])[CH:21]=[C:20]([CH2:32][CH3:33])[C:19]=1[C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([CH2:40]O)[CH:35]=1)[CH3:17].C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1(C)C=CC=CC=1.CCCCCC>[CH3:1][O:2][C:3](=[O:15])[CH2:4][C@H:5]1[C:9]2[CH:10]=[CH:11][C:12]([O:14][CH2:40][C:36]3[CH:35]=[C:34]([C:19]4[C:18]([CH2:16][CH3:17])=[CH:23][C:22]([O:24][CH2:25][CH2:26][CH2:27][S:28]([CH3:31])(=[O:29])=[O:30])=[CH:21][C:20]=4[CH2:32][CH3:33])[CH:39]=[CH:38][CH:37]=3)=[CH:13][C:8]=2[O:7][CH2:6]1
Reactant: CCc1cc(OCCCS(C)(=O)=O)cc(CC)c1-c1cccc(CO)c1
Reactant: COC(=O)C[C@@H]1COc2cc(O)ccc21
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: Cc1ccccc1
Solvent: CCCCCC
Product: CCc1cc(OCCCS(C)(=O)=O)cc(CC)c1-c1cccc(COc2ccc3c(c2)OC[C@H]3CC(=O)OC)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 92.8 %

Procedure:
A solution of methyl[(3S)-6-hydroxy-2,3-dihydro-1-benzofuran-3-yl]acetate (0.208 g, 1.00 mmol), {2′,6′-diethyl-4′-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methanol (0.377 g, 1.00 mmol) and tributylphosphine (0.399 mL, 1.60 mmol) in toluene (16 mL) was stirred, 1,1′-(azodicarbonyl)dipiperidine (0.404 g, 1.60 mmol) was added, and the mixture was stirred at room temperature for 2 hr under nitrogen atmosphere. Hexane (8 mL) was added to the reaction mixture, the precipitated insoluble substance was filtered off, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=30:70-70:30) to give the title compound (0.526 g, yield 93%) as a yellow oil.
Reaction SMILES: [NH2:1][CH:2]([C:37]1[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][CH:38]=1)[CH2:3][N:4]([CH2:15][C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=1[C:26]1[CH:31]=[C:30]([CH:32]([CH3:34])[CH3:33])[CH:29]=[CH:28][C:27]=1[O:35][CH3:36])[C:5](=[O:14])OCC1C=CC=CC=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+]>C1COCC1.C1(C)C=CC=CC=1>[Cl:43][C:40]1[CH:41]=[CH:42][C:37]([CH:2]2[CH2:3][N:4]([CH2:15][C:16]3[CH:21]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:19]=[CH:18][C:17]=3[C:26]3[CH:31]=[C:30]([CH:32]([CH3:33])[CH3:34])[CH:29]=[CH:28][C:27]=3[O:35][CH3:36])[C:5](=[O:14])[NH:1]2)=[CH:38][CH:39]=1
Reactant: COc1ccc(C(C)C)cc1-c1ccc(C(F)(F)F)cc1CN(CC(N)c1ccc(Cl)cc1)C(=O)OCc1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: COc1ccc(C(C)C)cc1-c1ccc(C(F)(F)F)cc1CN1CC(c2ccc(Cl)cc2)NC1=O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of benzyl [2-amino-2-(4-chlorophenyl)ethyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (30 mg, 0.05 mmol) in THF (2 mL) was added potassium bis(trimethylsilyl)amide (295 μL of a 0.5M solution in toluene, 0.147 mmol) The reaction was stirred at room temperature for 30 minutes and then quenched with saturated NH4Cl (15 mL). The resultant mixture was extracted with EtOAc (25 mL) and the organic layer was washed with H2O (15 mL) and brine (15 mL), dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography with 5% to 60% EtOAc/hexanes afforded 4-(4-chlorophenyl)-1-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}imidazolidin-2-one. Rf=0.46 (5% MeOH/CH2Cl2). LCMS=503.1 (M+1)+. 1H NMR (C6D6, 600 MHz, atropisomers observed; doubling of peaks.) δ 7.90-7.03 (m, 6H), 6.89-6.20 (m, 4H), 4.69-3.88 (m, 3H), 3.16 (s, 3H), 2.88-2.30 (m, 3H), 1.18-1.13 (m, 6H).
Reaction SMILES: [CH3:1][C:2]1[O:6][N:5]=[C:4]([CH:7]=O)[CH:3]=1.Cl.[NH2:10][N:11]1[CH2:15][CH2:14][NH:13][C:12]1=[O:16]>O>[CH3:1][C:2]1[O:6][N:5]=[C:4]([CH:7]=[N:10][N:11]2[CH2:15][CH2:14][NH:13][C:12]2=[O:16])[CH:3]=1
Reactant: NN1CCNC1=O
Reactant: Cc1cc(C=O)no1
Agent: Cl
Solvent: O
Product: Cc1cc(C=NN2CCNC2=O)no1
Reaction time: 1.5 h

Procedure:
14.0 pts. by wt. of 5-methyl-3-formyl-isoxazole are reacted with 25.6 pts. by wt. of 1-amino-2-oxo-imidazolidine hydrochloride in 100 pts. by vol. of water as in Example 25.1. After 90 minutes, the precipitate is filtered off, washed with water, dried and recrystallised from absolute acetonitrile. 12.5 pts. by wt. of 1-(5-methyl-isoxazol-3-yl-methyleneamino)-2-oxo-imidazolidine of melting point 195°-7° C. are obtained.
Reaction SMILES: CS(O[CH:6]([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][NH:12][C:13]1[CH:23]=[CH:22][C:16]([C:17]([O:19]CC)=[O:18])=[CH:15][CH:14]=1)(=O)=O.C([O-])(=[S:36])C.[K+]>CC(C)=O>[SH:36][CH:6]([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][NH:12][C:13]1[CH:23]=[CH:22][C:16]([C:17]([OH:19])=[O:18])=[CH:15][CH:14]=1
Reactant: CC([O-])=S
Reactant: CCCCCCCCCCC(CCCCCNc1ccc(C(=O)OCC)cc1)OS(C)(=O)=O
Agent: [K+]
Solvent: CC(C)=O
Product: CCCCCCCCCCC(S)CCCCCNc1ccc(C(=O)O)cc1

Procedure:
A mixture of 7.6 g. ethyl 4-(6-methanesulfonyloxyhexadecylamino)benzoate and 5.5 g. of potassium thioacetate in 200 ml. of acetone is stirred under reflux for 3 hours and evaporated. The residue is positioned between methylene chloride and water and the organic layer is separated, dried and evaporated. Recrystallization of the residual solid form hexane affords the product as a light, tan solid. Hydrolysis of the product by the method of Example 10 affords 4-(6-mercaptohexadecylamino)benzoic acid.
Reaction SMILES: [CH3:1][CH:2]([N:4]1[C:12](/[CH:13]=[CH:14]/[C@H:15]([OH:24])[CH2:16][C@H:17]([OH:23])[CH2:18][C:19]([O:21]C)=[O:20])=[C:11]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH3:3].[OH-].[Na+:33]>O>[CH3:3][CH:2]([N:4]1[C:12](/[CH:13]=[CH:14]/[CH:15]([OH:24])[CH2:16][CH:17]([OH:23])[CH2:18][C:19]([O-:21])=[O:20])=[C:11]([C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]1=2)[CH3:1].[Na+:33]
Reactant: COC(=O)C[C@@H](O)C[C@@H](O)/C=C/c1c(-c2ccc(F)cc2)c2ccccc2n1C(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(C)n1c(/C=C/C(O)CC(O)CC(=O)[O-])c(-c2ccc(F)cc2)c2ccccc21
Temperature: 25 °C
Reaction time: 72 h
Yield: 31.4 %

Procedure:
A 100 ml round bottom flask was loaded with fluvastatin methyl ester (4.0 g, 9.4 mmole), water (32 ml) and NaOH (0.39 g). The mixture was stirred for 3 days at room temperature then extracted with ethyl acetate (32 ml, 16 ml). The aqueous solution was evaporated, propan-2-ol (40 ml) was added and the mixture was stirred at room temperature over night. Precipitation occurred after scraping the mixture with spatula and stirring for another day. The product was isolated by filtration under nitrogen flow, washed with propan-2-ol (20 ml) and dried at 50° C. in a vacuum oven for 24 h to obtain 1.28 g (31%) of fluvastatin sodium crystal Form LXXVIII.
Reaction SMILES: O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:13]([O:15][C:16](=[O:37])[CH2:17][O:18][CH2:19]/[CH:20]=[CH:21]\[CH2:22][N:23]1[C:28](=[O:29])[CH2:27][CH2:26][CH2:25][C@@H:24]1[CH2:30][O:31]C(OCC)C)[CH3:14]>CCO>[CH2:13]([O:15][C:16](=[O:37])[CH2:17][O:18][CH2:19]/[CH:20]=[CH:21]\[CH2:22][N:23]1[C:28](=[O:29])[CH2:27][CH2:26][CH2:25][C@@H:24]1[CH2:30][OH:31])[CH3:14]
Reactant: CCOC(=O)COC/C=C\CN1C(=O)CCC[C@@H]1COC(C)OCC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CCO
Product: CCOC(=O)COC/C=C\CN1C(=O)CCC[C@@H]1CO
Reaction time: 18 h
Yield: 76.4 %

Procedure:
p-Toluenesulfonic acid hydrate (267 mg, 1.40 mmol) was added to a solution of {(Z)-4-[(R)-2-(1-ethoxyethoxymethyl)-6-oxo-piperidin-1-yl]-but-2-enyloxy}-acetic acid ethyl ester (from example 50, step 2, 477 mg, 1.33 mmol) in EtOH (6 mL). After 18 h at rt, the reaction was concentrated in vacuo and quenched with saturated aqueous NaHCO3 (20 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic phase was dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2→3% MeOH/CH2Cl2, gradient) afforded 290 mg (76%) of [(Z)-4-((R)-2-hydroxymethyl-6-oxo-piperidin-1-yl)-but-2-enyloxy]-acetic acid ethyl ester.
Reaction SMILES: C([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12](=[N:16][OH:17])[C:13]([NH2:15])=[O:14])(=O)C.[CH3:18]N.CO>CO>[OH:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:12](=[N:16][OH:17])[C:13]([NH:15][CH3:18])=[O:14]
Reactant: CN
Reactant: CC(=O)OCc1ccccc1C(=NO)C(N)=O
Solvent: CO
Product: CNC(=O)C(=NO)c1ccccc1CO
Yield: 67.4 %

Procedure:
A mixture of 2-(2-acetoxymethylphenyl)-2-hydroxyiminoacetamide (1.00 g, E/Z≠65/35), a 40% methylamine/methanol solution (2.1 ml) and methanol (6.3 ml) was stirred at 40° C. for 6 hours. After the mixture was cooled by allowing it to stand, the solvent was evaporated under reduced pressure to obtain the crude product (E/Z≠98/2). This crude product was purified by column chromatography on silica gel (ethyl acetate) and crystallized from ethyl acetate-hexane to obtain the title compound as crystals (594 mg, E/Z≠93/7, yield: 67.4%).
Reaction SMILES: [C:1]1([C@H:7]2[CH2:11][O:10][C:9](=[O:12])[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:16][C:17]([O:19]CC)=[O:18].[OH-].[Na+]>C1COCC1>[C:1]1([C@H:7]2[CH2:11][O:10][C:9](=[O:12])[N:8]2[CH2:16][C:17]([OH:19])=[O:18])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C1N[C@@H](c2ccccc2)CO1
Reactant: CCOC(=O)CBr
Agent: [H-]
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=C(O)CN1C(=O)OC[C@@H]1c1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 91.9 %

Procedure:
To a stirred, 0° C. solution of (S)-4-phenyloxazoldin-2-one (1.07 g, 6.54 mmol) in 15 mL of THF was added sodium hydride (0.32 g of a 60% oil dispersion, 8.0 mmol). When gas evolution had ceased (ca. 10 minutes), ethyl bromoacetate (0.87 mL, 7.8 mmol) was added. After 2 hours at 0° C., the mixture was treated with 50 mL of 2N aqueous NaOH, stirred rapidly for 1 hour at room temperature, and then partitioned between hexane (50 mL) and water (50 mL). The aqueous layer was separated, acidified with 6M aqueous H2SO4, and extracted with dichloromethane (2×200 mL). The combined organic phases were dried (Na2SO4) and concentrated to a thick oil, which was dissolved in 4 mL of warm toluene, seeded, and allowed to crystallize overnight; filtration gave 1.33 g (92%) of (S)-4-phenyloxazolidin-2-one-3-ylacetic acid: mp 106°-108° C.; [α]D22 +173° (c=2.0, CHCl3); IR (CHCl3) 3500-2500 (v. br), 1760 (br), 1480, 1460, 1430, 1230 cm-1 ; 2H NMR δ11.2 (br s, 1, COOH), 7.47-7.25 (m, 5, ArH), 5.05 (t, 1, J=8.4 Hz, OCH2CH), 4.72 (t, 1, J=8.8 Hz, one of OCH2CH), 4.32 (d, 1, J=18.4 Hz, one of NCH2), 4.17 (t, 1, J=8.4 Hz, one of OCH 2CH), 3.41 (d, 1, J=18.4 Hz, one of NCH2).
Reaction SMILES: [CH:1]1([OH:8])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[SH:9][CH2:10][C:11](O)=[O:12].C1(C)C=CC(S(O)(=O)=O)=CC=1>>[SH:9][CH2:10][C:11]([O:8][CH:1]1[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)=[O:12]
Reactant: O=C(O)CS
Reactant: OC1CCCCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Product: O=C(CS)OC1CCCCCC1

Procedure:
Into a 100 ml reaction flask equipped with stirrer, thermometer, reflux condenser and heating mantle are placed 28.5 grams of cycloheptanol; 9.2 grams of mercaptoacetic acid and 0.5 grams of paratoluene sulfonic acid. The reaction mass is heated to reflux and refluxed for a period of 10 hours. At the end of the 10 hour period, the reaction mass is washed with one 25 ml volume of water followed by drying over anhydrous sodium sulfate. The reaction mass is then distilled in a micro distillation apparatus yielding the compound having the structure ##STR115##
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][NH:11][C:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[N:15]=[CH:14][C:13]=2[N+:22]([O-])=O)=[CH:5][CH:4]=1.[H][H]>C1(C)C=CC=CC=1.[Pt]>[NH2:22][C:13]1[CH:14]=[N:15][C:16]2[C:21]([C:12]=1[NH:11][CH2:10][CH2:9][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=1)=[CH:20][CH:19]=[CH:18][CH:17]=2
Reactant: COc1ccc(CCNc2c([N+](=O)[O-])cnc3ccccc23)cc1
Reactant: [H][H]
Agent: [Pt]
Solvent: Cc1ccccc1
Product: COc1ccc(CCNc2c(N)cnc3ccccc23)cc1

Procedure:
Using the method of Example 26, 20.4 g (0.063 mole) of 4-[2-(4-methoxyphenyl)ethylamino]-3-nitroquinoline was reduced by hydrogen in 300 ml of toluene with 5% platinum on charcoal. The solvent was then evaporated to provide a residue of 3-amino-4-[2-(4-methoxyphenyl)ethylamino]quinoline. To this residue was added 28 g (0.19 mole) of triethyl orthoformate and the mixture was heated at about 125° C. for two hours. To this mixture was added about 100 ml of aqueous hydrochloric acid and the mixture was heated on a steam bath for thirty minutes. After cooling, the precipitate was separated by filtration, washed sequentially with isopropanol and diethyl ether, and dried. To the solid was added water and ammonium hydroxide, after which the mixture was cooled and the solid was separated by filtration. A portion (3.5 g) of the solid was dissolved in isopropanol, and acidified with hydrochloric acid. The solid was separated by filtration, washed with isopropanol and dried to provide 1-[2-(4-methoxyphenyl)ethyl]-1H-imidazo[4,5-c]quinoline hydrochloride hydrate, m.p. 209°-213° C. Analysis: Calculated for C19H17N3O.HCl.1/3H2O: %C, 66.0; %H, 5.4; %N, 12.2; Found: %C, 66.1; %H, 5.3; %N, 12.3.
Reaction SMILES: [Br:1]Br.[CH:3]1[C:20]2[C:7](=[C:8]3[C:17](=[CH:18][CH:19]=2)[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[S:10](=[O:22])(=[O:21])[NH:9]3)[N:6]=[CH:5][CH:4]=1.C(Cl)(Cl)Cl>O1CCOCC1.C(Cl)(Cl)Cl>[Br:1][C:19]1[CH:18]=[C:17]2[C:8](=[C:7]3[C:20]=1[CH:3]=[CH:4][CH:5]=[N:6]3)[NH:9][S:10](=[O:21])(=[O:22])[C:11]1[C:16]2=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: BrBr
Reactant: O=S1(=O)Nc2c(ccc3cccnc23)-c2ccccc21
Solvent: ClC(Cl)Cl
Solvent: C1COCCO1
Product: O=S1(=O)Nc2c(cc(Br)c3cccnc23)-c2ccccc21
Reaction time: 2 h
Yield: 64.6 %

Procedure:
Bromine (170 μl, 3.30 mmol) was added dropwise to a solution of 5H-6-thia-4,5-diaza-chrysene 6,6-dioxide 184 (467 mg, 1.65 mmol) in 1,4-dioxane/chloroform (1:1, 124 ml) at 0° C. After 2 h, chloroform (30 ml) was added and the resulting precipitate was collected by filtration. The solid was triturated from MeOH to give the title compound (385 mg, 64%).
Reaction SMILES: O1CCCC1.[C:6]([C:8]1([OH:26])[C:19]([CH3:24])([C:20]([F:23])([F:22])[F:21])[CH2:18][C:11]2([O:15][CH:14]([CH3:16])[CH:13]([CH3:17])[O:12]2)[CH:10]=[C:9]1[CH3:25])#[CH:7].[CH2:27]([SnH:31]([CH2:36][CH2:37][CH2:38][CH3:39])[CH2:32][CH2:33][CH2:34][CH3:35])[CH2:28][CH2:29][CH3:30]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:17][CH:13]1[CH:14]([CH3:16])[O:15][C:11]2([CH2:18][C:19]([CH3:24])([C:20]([F:21])([F:23])[F:22])[C:8](/[CH:6]=[CH:7]/[Sn:31]([CH2:32][CH2:33][CH2:34][CH3:35])([CH2:36][CH2:37][CH2:38][CH3:39])[CH2:27][CH2:28][CH2:29][CH3:30])([OH:26])[C:9]([CH3:25])=[CH:10]2)[O:12]1
Reactant: C#CC1(O)C(C)=CC2(CC1(C)C(F)(F)F)OC(C)C(C)O2
Reactant: CCCC[SnH](CCCC)CCCC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: CCCC[Sn](/C=C/C1(O)C(C)=CC2(CC1(C)C(F)(F)F)OC(C)C(C)O2)(CCCC)CCCC
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 81.4 %

Procedure:
Under argon, tetrakis(triphenylphosphine)palladium(0) (19 mg, 0.02 mmol) was initially charged in a round-bottom flask that had been dried by heating, and abs. tetrahydrofuran (5 ml) and 8-ethynyl-2,3,7,9-tetramethyl-9-(trifluoromethyl)-1,4-dioxaspiro[4.5]dec-6-en-8-ol (100 mg, 0.33 mmol) were added. Stirring at room temperature for 5 minutes was followed by the addition of tributyltin hydride (0.11 ml, 0.39 mmol). The resulting reaction mixture was stirred at 55° C. for 1 h and, after cooling to room temperature, water was added. The aqueous phase was repeatedly extracted thoroughly with dichloromethane, and the combined organic phases were then dried over magnesium sulfate, filtered and concentrated under reduced pressure. By final column chromatography purification of the resulting crude product (ethyl acetate/heptane gradient), it was possible to obtain 2,3,7,9-tetramethyl-8-[(E)-2-(tributylstannyl)vinyl]-9-(trifluoromethyl)-1,4-dioxaspiro[4.5]dec-6-en-8-ol (160 mg, 82% of theory) in the form of a colorless oil. 1H-NMR (400 MHz, CDCl3 δ, ppm) 6.33/6.31 (d, 1H), 5.97/5.92 (d, 1H), 5.51/5.42 (s, 1H), 4.24/3.64 (m, 2H), 2.46/2.35 (d, 1H), 1.92 (br. s, 1H, OH), 1.91/1.87 (d, 1H), 1.64/1.62 (s, 3H), 1.49 (m, 6H), 1.32-1.26 (m, 9H), 1.18 (m, 3H), 0.89 (m, 18H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[C:18]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=3)[N:17]=[C:16](S(C)(=O)=O)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C-:34]#[N:35].[Na+]>CS(C)=O.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[C:18]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=3)[N:17]=[C:16]([C:34]#[N:35])[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCN(c2cc(-c3cccc(C(F)(F)F)c3)nc(S(C)(=O)=O)n2)CC1
Reactant: [C-]#N
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: CC(C)(C)OC(=O)N1CCN(c2cc(-c3cccc(C(F)(F)F)c3)nc(C#N)n2)CC1
Temperature: 25 °C
Reaction time: 24 h
Yield: 35.9 %

Procedure:
To a stirring solution of 4-[2-methanesulfonyl-6-(3-trifluoromethyl-phenyl)-pyrimidin-4-yl]-piperazine-1-carboxylic acid tert-butyl ester (720 mg) in dimethyl sulphoxide (17 ml) was added sodium cyanide (72.5 mg). The resulting solution was stirred at room temperature for 24 hrs. After diluting with ethyl acetate (100 ml), then washed with water (4×50 ml), brine (50 ml), dried over MgSO4 and concentrated in vacuo. The residual solid was columned on silica gel using heptane and ethyl acetate (2:1) as eluant to give a white solid (230 mg).
Reaction SMILES: [C:1]1([N:7]2[C:11](=[O:12])[CH2:10][S:9][C:8]2=[S:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:14]([O:16][C:17](OCC)(OCC)[CH2:18][CH3:19])[CH3:15].C(OC(=O)C)(=O)C>>[CH2:14]([O:16][C:17](=[C:10]1[S:9][C:8](=[S:13])[N:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:11]1=[O:12])[CH2:18][CH3:19])[CH3:15]
Reactant: CCOC(CC)(OCC)OCC
Reactant: O=C1CSC(=S)N1c1ccccc1
Solvent: CC(=O)OC(C)=O
Product: CCOC(CC)=C1SC(=S)N(c2ccccc2)C1=O

Procedure:
A mixture of 8.4 g. (0.04 m.) of 3-phenylrhodanine, 21 g. (0.12 m.) of triethylorthopropionate and 80 ml. of acetic anhydride is heated under reflux for six hours, cooled and filtered. The solid is washed with 50% aqueous acetic acid to afford 5-(1'-ethoxypropylidene)-3-phenylrhodanine, m.p. 178°-181°C.