Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O.[OH-].[Li+].C[O:5][C:6](=[O:37])[CH2:7][C:8]1[C:17]([CH3:18])=[C:16]([C:19]2[CH:24]=[CH:23][C:22]([S:25]([C:28]3[CH:33]=[C:32]([F:34])[CH:31]=[C:30]([F:35])[CH:29]=3)(=[O:27])=[O:26])=[CH:21][CH:20]=2)[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:36])[CH:14]=2)[CH:9]=1>C1COCC1.O>[F:34][C:32]1[CH:33]=[C:28]([S:25]([C:22]2[CH:21]=[CH:20][C:19]([C:16]3[C:15]4[C:10](=[CH:11][CH:12]=[C:13]([F:36])[CH:14]=4)[CH:9]=[C:8]([CH2:7][C:6]([OH:37])=[O:5])[C:17]=3[CH3:18])=[CH:24][CH:23]=2)(=[O:27])=[O:26])[CH:29]=[C:30]([F:35])[CH:31]=1
Reactant: COC(=O)Cc1cc2ccc(F)cc2c(-c2ccc(S(=O)(=O)c3cc(F)cc(F)c3)cc2)c1C
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: Cc1c(CC(=O)O)cc2ccc(F)cc2c1-c1ccc(S(=O)(=O)c2cc(F)cc(F)c2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 98.5 %

Procedure:
Lithium hydroxide monohydrate (0.019 g, 0.45 mmol) was added to a stirred solution of {4-[4-(3,5-difluorobenzenesulfonyl)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (0.055 g, 0.11 mmol) in a 3:1 THF—H2O mixture (4 mL). The reaction mixture was stirred for 16 hours at room temperature. The THF was distilled off under reduced pressure, and the crude residue was diluted with water, acidified [pH˜2] via the drop-wise addition of an aqueous solution of hydrochloric acid (6.0 N). The mixture was extracted twice with ethyl acetate. The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. Trituration with hexanes afforded {4-[4-(3,5-difluorobenzenesulfonyl)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid (0.051 g, 96%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.48 (br. s., 1 H) 8.22 (d, J=7.82 Hz, 2 H) 7.97-8.05 (m, 1 H) 7.87-7.92 (m, 3 H) 7.74 (t, J=9.29 Hz, 1 H) 7.55 (d, J=7.82 Hz, 2 H) 7.35-7.42 (m, 1 H) 6.66 (d, J=11.74 Hz, 1 H) 3.84 (s, 2 H) 2.03 (s, 3 H) MS calcd. for C25H16F3O4S [(M−H)−] 469, obsd. 469.4.
Reaction SMILES: [Cl:1][C:2]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:3]=1[O:4][C:5]1[C:10]([C:11]([N:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[NH:16][CH2:15][CH2:14]2)=[O:12])=[CH:9][C:8]([F:23])=[CH:7][N:6]=1.C[O:30][C:31](=[O:36])[CH:32]([CH3:35])[CH:33]=O.C([Sn](Cl)(Cl)CCCC)CCC.C1([SiH3])C=CC=CC=1>O.C1COCC1>[Cl:1][C:2]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:3]=1[O:4][C:5]1[C:10]([C:11]([N:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:16]([CH2:33][CH:32]([CH3:35])[C:31]([OH:36])=[O:30])[CH2:15][CH2:14]2)=[O:12])=[CH:9][C:8]([F:23])=[CH:7][N:6]=1
Reactant: COC(=O)C(C)C=O
Reactant: O=C(c1cc(F)cnc1Oc1cc(Cl)ccc1Cl)N1CCNc2ccccc21
Agent: CCCC[Sn](Cl)(Cl)CCCC
Agent: [SiH3]c1ccccc1
Solvent: C1CCOC1
Solvent: O
Product: CC(CN1CCN(C(=O)c2cc(F)cnc2Oc2cc(Cl)ccc2Cl)c2ccccc21)C(=O)O
Temperature: 150 °C
Yield: 7.3 %

Procedure:
To a solution of [2-(2,5-dichloro-phenoxy)-5-fluoro-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone (25.1 mg, 0.06 mmol, 1.0 equiv; Example 147) in a 1:1 mixture of THF and water (1 mL) was added 2-methyl-3-oxo-propionic acid methyl ester (27.9 mg, 0.24 mmol, 4.0 equiv; [CAS RN 51673-64-4]), dibutyltin dichloride (1.8 mg, 0.006 mmol, 0.1 equiv; [CAS RN 683-18-1]) and phenylsilane (13.0 mg, 15 μL, 0.12 mmol, 2.0 equiv; [CAS RN 694-53-1]). The reaction mixture was heated by microwave irradiation to 150° C. for 1.5 h. Removal of the solvent mixture under reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water provided 2.2 mg (7%) of the title compound as a light yellow solid. MS (ISP): 504.0 [M+H]+.
Reaction SMILES: Br[C:2]1[NH:3][C:4]2[C:9]([N:10]=1)=[C:8]([N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)[N:7]=[C:6]([CH2:17][CH2:18][O:19][CH3:20])[N:5]=2.[NH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([CH3:28])[CH:23]=1>>[CH3:20][O:19][CH2:18][CH2:17][C:6]1[N:5]=[C:4]2[C:9]([N:10]=[C:2]([NH:21][C:22]3[CH:23]=[C:24]([CH3:28])[CH:25]=[CH:26][CH:27]=3)[NH:3]2)=[C:8]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[N:7]=1
Reactant: Cc1cccc(N)c1
Reactant: COCCc1nc(N2CCOCC2)c2nc(Br)[nH]c2n1
Product: COCCc1nc(N2CCOCC2)c2nc(Nc3cccc(C)c3)[nH]c2n1
Temperature: 190 °C
Yield: 81 %

Procedure:
A suspension of 8-bromo-2-(2-methoxy-ethyl)-6-morpholin-4-yl-9H-purine (0.42 g, 1.2 mmol) in m-toluidine (0.5 mL, 3.8 eq) in a tightly stoppered flask was heated at 190° C. for 15 minutes. Column chromatography afforded [2-(2-methoxy-ethyl)-6-morpholin-4-yl-9H-purin-8-yl]-m-tolyl-amine (0.36 g, 81%) as an off-white solid.
Reaction SMILES: Br[C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:9][C@@H:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]1.C([O-])([O-])=O.[Cs+].[Cs+].O>C1(C)C=CC=CC=1.C12(PC34CC(CC3)CC4)CC(CC1)CC2.CN(CC1[C-]([Pd]Cl)C=CC=1)C.[CH-]1C=CC=C1.[Fe+2].CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:8][C:7]1[C:2]([NH:9][C@@H:10]2[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]2)=[N:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H](N)C1
Reactant: Cc1cccnc1Br
Agent: CN(C)Cc1ccc[c-]1[Pd]Cl
Agent: [Fe+2]
Agent: [Pd+2]
Solvent: Cc1ccccc1
Solvent: O
Product: Cc1cccnc1N[C@@H]1CCCN(C(=O)OC(C)(C)C)C1
Temperature: 110 °C
Reaction time: 48 h
Yield: 51.2 %

Procedure:
To a solution of 2-bromo-3-methylpyridine (75.0 g, 436 mmol) and tert-butyl (3R)-3-aminopiperidine-1-carboxylate (87.3 g, 436 mmol) in toluene (1.2 L) were added Cs2CO3 (426 g, 1.31 mol), 2-(dimethylaminomethyl)ferrocen-1-yl-palladium(II) chloride dinorbornylphosphine (MFCD05861622) (1.56 g, 4.36 mmol) and Pd(OAc)2 (0.490 g, 2.18 mmol) under N2 atmosphere. The mixture was stirred at 110° C. for 48 h. The mixture was cooled to room temperature then poured into water (500 mL) and extracted with EtOAc (3×300 mL). The organic layers were dried over Na2SO4, filtered, and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography to give the title compound as a yellow solid (65 g, 60%).
Reaction SMILES: [CH2:1]([C:5]1[N:6]=[C:7]([CH3:27])[NH:8][C:9](=[O:26])[C:10]=1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=2)=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:35][N:36]1[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2[N:38]=[N:37]1.CN(C)C=O>C(OCC)(=O)C>[N:36]1([CH2:35][N:8]2[C:9](=[O:26])[C:10]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([C:18]4[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=4)=[CH:14][CH:13]=3)=[C:5]([CH2:1][CH2:2][CH2:3][CH3:4])[N:6]=[C:7]2[CH3:27])[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2[N:38]=[N:37]1
Reactant: CCCCc1nc(C)[nH]c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Reactant: ClCn1nnc2ccccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCCCc1nc(C)n(Cn2nnc3ccccc32)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Temperature: 90 °C
Reaction time: 2 h
Yield: 33 %

Procedure:
A mixture of 4′-[(4-butyl-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (1.22 g), potassium carbonate (0.94 g), 1-(chloromethyl)-1H-1,2,3-benzotriazole (0.62 g) and N,N-dimethylformamide (20 mL) was stirred at 90° C. for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.55 g, 33%).
Reaction SMILES: Br[CH:2]([C:7]1[CH:12]=[CH:11][C:10]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:9][CH:8]=1)[C:3]([O:5][CH3:6])=[O:4].[C:20]1([OH:26])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CO>[O:26]([CH:2]([C:7]1[CH:12]=[CH:11][C:10]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:9][CH:8]=1)[C:3]([O:5][CH3:6])=[O:4])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: Oc1ccccc1
Reactant: COC(=O)C(Br)c1ccc(Oc2ccccc2)cc1
Solvent: CO
Product: COC(=O)C(Oc1ccccc1)c1ccc(Oc2ccccc2)cc1
Yield: 89.8 %

Procedure:
Methyl α-bromo-α-[p-(phenoxy)phenyl]acetate (6.42 g) is reacted with 2.35 g of phenol in methanol as in Example 16 to afford 6 g of a yellow liquid after distillation (154° C. at 0.15 mm). A 2.2 g portion is purified by chromatography on silica gel (60 g) with benzene eluent to give the product as a white solid, mp 75.5°-77° C. (from pet. ether).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:17])[C:4]([NH:12][C:13]([O:15][CH3:16])=[O:14])=[CH:5][CH:6]1[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1>CO.C(Cl)Cl>[CH3:1][O:2][C:3](=[O:17])[CH:4]([NH:12][C:13]([O:15][CH3:16])=[O:14])[CH2:5][CH:6]1[CH2:7][CH2:8][O:9][CH2:10][CH2:11]1
Reactant: COC(=O)NC(=CC1CCOCC1)C(=O)OC
Solvent: ClCCl
Solvent: CO
Product: COC(=O)NC(CC1CCOCC1)C(=O)OC
Reaction time: 72 h
Yield: 78.7 %

Procedure:
A solution of 2-Methoxycarbonylamino-3-(tetrahydro-pyran-4-yl)-acrylic acid methyl ester (0.14 g, 0.57 mmol) in MeOH (2.1 mL) and CH2Cl2 (0.21 mL) was degassed with argon for 2 min. (S,S)-Me-BPE-Rh (0.02 g, 0.03 mmol) was added and the solution was degassed with argon for an additional 2 min. The solution was shaken on a Parr apparatus under an H2 atmosphere (65 psi) for 3 days. The reaction was concentrated and the crude oil was purified by column chromatography (SiO2, 20→100% EtOAc in Hexanes) to provide 2-Methoxycarbonylamino-3-(tetrahydro-pyran-4-yl)-propionic acid methyl ester (0.11 g, 77%). LCMS-ESI+: calc'd for C11H19NO5: 245.13 (M+); Found: 246.1 (M+H+).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[N:6][CH:7]=1.C(C1C=CC(S([N:36]=[N+:37]=[N-:38])(=O)=O)=CC=1)CCCCCCCCCCC.[NH4+].[Cl-]>O1CCCC1>[N:36]([C:4]1[C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:11])([CH3:13])[CH3:12])=[N:6][CH:7]=[C:2]([F:1])[CH:3]=1)=[N+:37]=[N-:38]
Reactant: CCCCCCCCCCCCc1ccc(S(=O)(=O)N=[N+]=[N-])cc1
Reactant: CC(C)(C)C(=O)Nc1ccc(F)cn1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CC(C)(C)C(=O)Nc1ncc(F)cc1N=[N+]=[N-]
Temperature: 25 °C
Reaction time: 3 h
Yield: 17 %

Procedure:
To a −78° C. solution of N-(5-fluoropyridin-2-yl)-2,2-dimethylpropanamide (1.34 g, 6.83 mmol) in tetrahydrofuran (25 mL) was added tert-butyl]ithium (1.31 mL of a 1.7 M solution, 20.5 mmol) drop wise. After 3 h at −78° C., 4-dodecylbenzenesulfonyl azide (3.60 g, 10.2 mmol) was added at the reaction was allowed to warm to room temperature. After 1 h, saturated aqueous NH4Cl was added, and the tetrahydrofuran was removed via rotary evaporator. Dichloromethane was added, the layers separated and the aqueous phase backwashed with DCM. The combined organics were dried over magnesium sulfate, filtered and concentrated and the residue purified by two successive silica gel chromatographies (10%→80% EtOAc/hexanes, then 5%→42% EtOAc/hexanes) to give the title compound (0.275 g). MS 234.0 (M+1).
Reaction SMILES: [N].N1C=CC=C1.[C:7]([C:9]1[C:10]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[S:27][CH:28]=[CH:29][C:30]=3[N+:31]([O-:33])=[O:32])=[CH:22][CH:21]=2)=[C:11]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[N:12]([CH3:14])[CH:13]=1)#[N:8].[Br:34]NC(=O)CCC(N)=O>C(Cl)Cl>[Br:34][C:13]1[N:12]([CH3:14])[C:11]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:10]([C:20]2[CH:21]=[CH:22][C:23]([C:26]3[S:27][CH:28]=[CH:29][C:30]=3[N+:31]([O-:33])=[O:32])=[CH:24][CH:25]=2)[C:9]=1[C:7]#[N:8]
Reactant: NC(=O)CCC(=O)NBr
Reactant: CCOC(=O)c1c(-c2ccc(-c3sccc3[N+](=O)[O-])cc2)c(C#N)cn1C
Agent: [N]
Solvent: c1cc[nH]c1
Solvent: ClCCl
Product: CCOC(=O)c1c(-c2ccc(-c3sccc3[N+](=O)[O-])cc2)c(C#N)c(Br)n1C
Temperature: 25 °C
Reaction time: 18 h

Procedure:
The title compound is prepared in a manner analogous to the procedure set forth in Scheme XXIII, step A wherein the starting pyrrole nitrogen is already methylated. For example, to a solution of ethyl 4-cyano-1-methyl-3-[4-(3-nitro(2-thienyl))phenyl]pyrrole-2-carboxylate, prepared directly above (1.0 mmol) in methylene chloride in an ice bath add N-bromo-succinamide (1.5 mmol). Allow the reaction to warm to room temperature and stir for 18 hours. After this time, wash reaction with water while extracting with ethyl acetate. Dry organic layer with sodium sulfate, filter and concentrate in vacuo to provide the title compound. Use as crude in the next step.
Reaction SMILES: [CH2:1]([C:3]1[N:11]2[C:6]([CH2:7][O:8][C:9]3[C:15]([N+:16]([O-])=O)=[CH:14][CH:13]=[CH:12][C:10]=32)=[C:5]([C:19]([OH:21])=[O:20])[N:4]=1)[CH3:2]>CO>[CH2:1]([C:3]1[N:11]2[C:6]([CH2:7][O:8][C:9]3[C:15]([NH2:16])=[CH:14][CH:13]=[CH:12][C:10]=32)=[C:5]([C:19]([OH:21])=[O:20])[N:4]=1)[CH3:2]
Reactant: CCc1nc(C(=O)O)c2n1-c1cccc([N+](=O)[O-])c1OC2
Solvent: CO
Product: CCc1nc(C(=O)O)c2n1-c1cccc(N)c1OC2

Procedure:
Ethyl 6-Nitro-3-carboxy-4H-imidazo[5,1-c]-1,4-benzoxazine was reduced shaken in MeOH under 40 p.s.i. H2 with 20 weight percent of 10% Pd/C (Degussa) for 1 h then filtered and the solvent evaporated. The compound was purified directly by column chromatograph (EtOAc/hexane) to yield Ethyl 6-Amino-3-carboxy-4H-imidazo[5,1-c]-1,4-benzoxazine 1H (DMSO-d6) 8.41 (s, 1H), 6.98 (m, 1H), 6.82 (m, 1H), 6.43 (m, 1H), 5.28 ((s, 2H), 4.23 (q, 2H, J=6.2 Hz), 1.27 (t, 2H, J=6.2 Hz) purity 92% MS (m/e): 232 (MH+).
Reaction SMILES: [C:1]([O:5][C:6](=[O:22])[CH2:7][CH2:8][N:9]1[CH2:14][CH2:13][S:12][CH:11]([C:15]2[CH:20]=[CH:19][C:18](Br)=[CH:17][CH:16]=2)[CH2:10]1)([CH3:4])([CH3:3])[CH3:2].CNCCNC.[Na+].[I-:30]>O1CCOCC1.[Cu]I>[C:1]([O:5][C:6](=[O:22])[CH2:7][CH2:8][N:9]1[CH2:14][CH2:13][S:12][CH:11]([C:15]2[CH:20]=[CH:19][C:18]([I:30])=[CH:17][CH:16]=2)[CH2:10]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)CCN1CCSC(c2ccc(Br)cc2)C1
Reactant: [I-]
Agent: [Cu]I
Agent: CNCCNC
Agent: [Na+]
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)CCN1CCSC(c2ccc(I)cc2)C1
Temperature: 130 °C
Yield: 77.7 %

Procedure:
To a degassed solution of 3-[2-(4-bromo-phenyl)-thiomorpholin-4-yl]-propionic acid tert-butyl ester (22.15 g; 57.33 mmol) and N,N′-dimethylethylenediamine (3.05 mL; 28.7 mmol) in 1,4-dioxane (250 mL) was added CuI (1.09 g; 5.73 mmol), and NaI (21.48 g; 143.33 mmol). The resulting mixture was heated at 130° C., for 4 days, in sealed flask. After cooling to RT the mixture was concentrated in vacuol and purified by column chromatography (SiO2, Et2O/hexanes 2:3) to afford 3-[2-(4-iodo-phenyl)-thiomorpholin-4-yl]-propionic acid tert-butyl ester (19.30 g).
Reaction SMILES: [N+]([C:4]1[CH:24]=[CH:23][C:7]([CH:8]=[CH:9][S:10]([NH:13][C:14](=[NH:22])[C:15]2C=CC(N)=CC=2)(=[O:12])=[O:11])=[CH:6][CH:5]=1)([O-])=O.Cl.C(N)(=N)C.[OH-].[Na+].C(S(Cl)(=O)=O)=CC1C=CC=CC=1>CC(C)=O>[CH:9]([S:10]([NH:13][C:14](=[NH:22])[CH3:15])(=[O:12])=[O:11])=[CH:8][C:7]1[CH:23]=[CH:24][CH:4]=[CH:5][CH:6]=1
Reactant: N=C(NS(=O)(=O)C=Cc1ccc([N+](=O)[O-])cc1)c1ccc(N)cc1
Agent: CC(=N)N
Agent: Cl
Agent: O=S(=O)(Cl)C=Cc1ccccc1
Solvent: CC(C)=O
Product: CC(=N)NS(=O)(=O)C=Cc1ccccc1
Yield: 76 %

Procedure:
Addition of 50% sodium hydroxide (4.0 g., 0.05 mole) to a solution of 4-aminobenzamidine hydrochloride (0.5 mole) in 10 ml. of water affords 4-aminobenzamidine free base. Acetone (50 ml.) is added to the liberated free base and the mixture cooled to 5° C. 4-Nitrostyrylsulfonyl chloride is added to the mixture in a period of 5 min. while maintaining a temperature below 15° C. The mixture is stirred for 10 min., the reaction mixture concentrated under reduced pressure provides a residue which diluted with 100 ml. of water and neutralized with 3N hyrochloric acid affords a pale yellow solid precipitate. The precipitate is collected, washed thoroughly with water and then triturated first with isopropanol and then with ether to yield 7.3 g. (84%) of N-(4-NITROSTYRYLSULFONYL)-4-AMINOBENZAMIDINE, m.p. 188°-189° C. (b) A mixture of acetamidine hydrochloride (28.8 g., 0.15 mole) and 50% sodium hydroxide (12.0 g., 0.15 mole) in 150 ml. of acetone is stirred for a period of 10 min. to liberate the free base. A solution of styrylsulfonyl chloride (10.1 g., 0.05 mole) in 50 ml. of acetone is added dropwise to the mixture at a temperature of 20°-25° C. with stirring. After further stirring for 10 min., the mixture is concentrated under reduced pressure to remove acetone, the concentrate diluted with 200 ml. of water and acidified with 3N hydrochloric acid to provide a precipitate. The precipitate is collected, dissolved in chloroform and the chloroform extract dried. Evaporation of the chloroform solvent under reduced pressure provides a white solid, m.p. 130°-134° C. which is crystallized from isopropyl acetate affording 8.5 g. (76% yield) of N-(STYRYLSULFONYL)ACETAMIDINE, m.p. 134.5°-137.0° C. (corr.).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18](Cl)=[O:19])=[CH:14][CH:13]=2)=[CH:8][CH:7]=1.[NH:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1>>[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)=[O:19])=[CH:14][CH:13]=2)=[CH:8][CH:7]=1
Reactant: O=C(Cl)c1ccc(-c2ccc(OCCCCl)cc2)cc1
Reactant: C1CCNC1
Product: O=C(c1ccc(-c2ccc(OCCCCl)cc2)cc1)N1CCCC1

Procedure:
The product from Example 10D and pyrrolidine were processed as described in Example 10E to provide the title compound.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=2)=[N:4][C:3]=1[C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][C:26]([CH:29]=O)=[CH:25][CH:24]=2)=[CH:19][CH:18]=1.[NH2:31][OH:32]>>[CH3:1][C:2]1[O:6][C:5]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=2)=[N:4][C:3]=1[C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][C:26]([CH:29]=[N:31][OH:32])=[CH:25][CH:24]=2)=[CH:19][CH:18]=1
Reactant: NO
Reactant: Cc1oc(-c2ccc(C(F)(F)F)cc2)nc1-c1ccc(-c2ccc(C=O)cc2)cc1
Product: Cc1oc(-c2ccc(C(F)(F)F)cc2)nc1-c1ccc(-c2ccc(C=NO)cc2)cc1

Procedure:
This compound was prepared from 4′-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-yl]-biphenyl-4-carbaldehyde, and hydroxylamine in substantially the same manner, as described in Example 1 step a, and was obtained as an off-white solid; MS m/e 422 (M+);
Reaction SMILES: [CH:1](=[CH:8][C:9](=[O:11])[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.F[B-](F)(F)F.O1CCCC1>CO>[C:2]1([CH:1]=[CH:8][CH:9]([OH:11])[CH3:10])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(=O)C=Cc1ccccc1
Agent: F[B-](F)(F)F
Agent: c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1
Solvent: CO
Solvent: C1CCOC1
Product: CC(O)C=Cc1ccccc1
Yield: 34.1 %

Procedure:
In a 200 ml stainless steel autoclave were charged 5 g (34.2 mmole) of benzalacetone and 0.213 g (0.171 mmole) of ##STR24## ((+)-BINAP)}BF4 synthesized in Example 4, and 3 ml of tetrahydrofuran and 2 ml of methanol were added thereto, followed by allowing the mixture to react at 30° C. under a hydrogen pressure of 50 kg/cm2 for 45 hours. The solvent was removed by distillation under reduced pressure (10 mmHg), and the reaction product was analyzed by GLC (PEG HT, 25 m, produced by Gasukuro Kogyo K. K.) to find the conversion to be 34.5%. The product was separated into the unreacted ketone and the hydrogenation product by silica gel column chromatography (eluent: hexane/ethyl acetate=4/1 by volume) to obtain 1.73 g of 4-phenyl-3-buten-2-ol having a purity of 89%. {α}25 D : +18.1°(c=5, CS2).
Reaction SMILES: C1C=C(Cl)C=C(C(OO)=[O:9])C=1.[F:12][C:13]1[C:20]([O:21][CH3:22])=[C:19]([CH:23]=[CH2:24])[CH:18]=[CH:17][C:14]=1[C:15]#[N:16]>C(Cl)Cl>[F:12][C:13]1[C:20]([O:21][CH3:22])=[C:19]([CH:23]2[CH2:24][O:9]2)[CH:18]=[CH:17][C:14]=1[C:15]#[N:16]
Reactant: C=Cc1ccc(C#N)c(F)c1OC
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: COc1c(C2CO2)ccc(C#N)c1F
Temperature: 25 °C
Reaction time: 60 h

Procedure:
mCPBA (85%, 9.9 g, 48.9 mmol) was added to the solution of 2-fluoro-3-methoxy-4-vinylbenzonitrile (3.4 g, 19.2 mmol) in 160 mL of DCM at 0° C. The mixture was stirred at room temperature for 60 hours before being diluted with 300 mL of DCM and cooled to 0° C. The mixture was washed subsequently with saturated NaHCO3 (50 mL), aqueous Na2SO3 (2×50 mL), 5% NaOH (50 mL) and brine. The organic layer was concentrated, and the residue was purified by column chromatography (PE:EtOAc=5:1) to afford 2-fluoro-3-methoxy-4-(oxiran-2-yl)benzonitrile: 1H NMR (400 MHz, CDCl3) δ 7.24 (d, J=7.6 Hz, 1H), 6.98 (d, J=7.6 Hz, 1H), 4.14-4.18 (m, 1H), 4.03 (s, 3H), 3.17-3.19 (m, 1H), 2.63-2.66 (m, 1H); MS m/z 194 (M+1)+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:31]#[N:32])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:24][C:25]3([CH3:29])[CH2:28][O:27][CH2:26]3)[C:17]([O:19]C(C)(C)C)=[O:18])[C:10](=[O:30])[CH:9]=2)[CH:7]=1.C(O)C.[OH-].[Li+].Cl>O1CCCC1.[Cl-].[NH4+].C(OCC)(=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:31]#[N:32])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:24][C:25]3([CH3:29])[CH2:28][O:27][CH2:26]3)[C:17]([OH:19])=[O:18])[C:10](=[O:30])[CH:9]=2)[CH:7]=1
Reactant: COc1cn(C(CC2(C)COC2)C(=O)OC(C)(C)C)c(=O)cc1-c1cc(Cl)ccc1C#N
Agent: Cl
Agent: [Cl-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCO
Solvent: CCOC(C)=O
Product: COc1cn(C(CC2(C)COC2)C(=O)O)c(=O)cc1-c1cc(Cl)ccc1C#N
Temperature: 25 °C
Reaction time: 7 h

Procedure:
340 mg (741 μmol) of tert-butyl 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]-3-(3-methyloxetan-3-yl)propanoate (racemate) were dissolved in 5 ml of tetrahydrofuran, 2.5 ml of ethanol and 2.5 ml of water, and 3.7 ml (3.7 mmol, 5 eq.) of aqueous lithium hydroxide solution (1M) were added. The mixture was stirred at room temperature for another 7 h and then diluted with 20 ml of saturated aqueous ammonium chloride solution and 30 ml of ethyl acetate and adjusted to pH 4-5 using aqueous hydrochloric acid (1N). The phases were separated and the aqueous phase was extracted three times with 10 ml of ethyl acetate. The combined organic phases were dried over magnesium sulphate and filtered, and the solvent was removed under reduced pressure. The crude product was used for the next step without further purification. Yield: 275 mg (purity 95%, 88% of theory)
Reaction SMILES: [C:1]([C@H:5]1[CH2:13][CH2:12][C@H:11]2[C@H:14]3[C@H:24]([CH2:25][CH2:26][C@:6]12[CH2:7][C:8]([OH:10])=[O:9])[C@:22]1([CH3:23])[C:17](=[CH:18][C:19](=[O:27])[CH2:20][CH2:21]1)[N:16]([C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:15]3)([O:3]C)=[O:2].O.O[Li].O.OS([O-])(=O)=O.[Na+]>O1CCOCC1>[C:1]([C@H:5]1[CH2:13][CH2:12][C@H:11]2[C@H:14]3[C@H:24]([CH2:25][CH2:26][C@:6]12[CH2:7][C:8]([OH:10])=[O:9])[C@:22]1([CH3:23])[C:17](=[CH:18][C:19](=[O:27])[CH2:20][CH2:21]1)[N:16]([C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:15]3)([OH:3])=[O:2]
Reactant: COC(=O)[C@H]1CC[C@H]2[C@@H]3CN(C(C)(C)C)C4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12CC(=O)O
Agent: O=S(=O)([O-])O
Agent: [Li]O
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: CC(C)(C)N1C[C@H]2[C@@H]3CC[C@H](C(=O)O)[C@@]3(CC(=O)O)CC[C@@H]2[C@@]2(C)CCC(=O)C=C12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 17β-carbomethoxy-6-t-butylcarboxy-6-azaandrost-4-en-3-one (15.4 g, 36 mmol), from part E, in dioxane (150 mL) and water (100 mL) is treated with LiOH.H2O (3.31 g, 79 mmol) and stirred overnight on a water bath. The reaction is poured into saturated aqueous NaHSO4 (150 mL), extracted with methylene chloride (3×100 mL), extracts washed with saturated aqueous NaCl, dried over MgSO4 and concentrated to a volume of 100 mL. At this point crystals begin to form and 2:1 hexanes/ethyl acetate (50 mL) is added, the mixture triturated, cooled to room temperature and 17β-carboxy-6-t-butylcarboxy-6-azaandrost-4-en-3-one collected as a fluffy white powder; yield: 9.44 g (63%); m.p. 215°-216° C. Anal. Calcd. for C24H35NO5.1/4H2O; C, 68.30; H, 8.48; N, 3.32. Found: C, 68.45; H, 8.41; N, 3.28.