Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH:2]([CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH:3]=[CH2:4].[C:12](=[O:15])([O-])[O-].[Na+].[Na+].[OH2:18]>O1CCCC1>[C:12]1(=[O:15])[N:1]([CH:2]([CH2:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH:3]=[CH2:4])[C:5](=[O:18])[C:6]2=[CH:11][CH:10]=[CH:9][CH:8]=[C:7]12
Reactant: O
Reactant: O=C([O-])[O-]
Reactant: C=CC(N)Cc1ccccc1
Agent: [Na+]
Solvent: C1CCOC1
Product: C=CC(Cc1ccccc1)N1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
(RS)-3-Amino-4-phenyl-1-butene (1.2 g, 8.0 mmol) was dissolved in tetrahydrofuran (20 ml). To the solution, a solution of N-carbethoxyphthalimido (2.2 g, 10.0 mmol) in water (20 ml) and anhydrous sodium carbonate (1.06 g, 10.0 mmol) was added and stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure to remove tetrahydrofuran, followed by extraction with ethyl acetate.
Reaction SMILES: [CH3:1][C:2]([NH:4][C:5]1[C:10]([O:11][CH3:12])=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:3].Cl[S:14]([OH:17])(=O)=[O:15].S(Cl)(Cl)(=O)=O.[CH2:23]([NH2:27])[CH2:24][CH2:25][CH3:26]>O1CCCC1>[C:2]([NH:4][C:5]1[CH:6]=[C:7]([S:14]([NH:27][CH2:23][CH2:24][CH2:25][CH3:26])(=[O:17])=[O:15])[CH:8]=[CH:9][C:10]=1[O:11][CH3:12])(=[O:3])[CH3:1]
Reactant: COc1ccccc1NC(C)=O
Reactant: O=S(=O)(O)Cl
Reactant: CCCCN
Solvent: O=S(=O)(Cl)Cl
Solvent: C1CCOC1
Product: CCCCNS(=O)(=O)c1ccc(OC)c(NC(C)=O)c1
Temperature: 25 °C
Yield: 92.4 %

Procedure:
As shown in Eq. 1 (above), o-acetanisidide (100 gms., 0.605 mole) was added in portions to 200 ml of chlorosulfonic acid at about 50° C. (cooling was necessary). After the addition, the amber solution was heated at about 50° to 60° C. for four hours, cooled to room temperature and carefully added to an ice water mixture (1.5 kg). A white precipitate was collected, washed free of acid, and pressed dry. A portion of sulfonyl chloride (0.100 mole) was dissolved in 100 ml of tetrahydrofuran and treated with 16.1 gms (0.221 mole) of n-butylamine (exotherm to 50° C.). The reaction mixture was refluxed an additional 15 minutes, the condenser removed, and the solvent removed by heating. The white crystalline solid that remained was slurried with 100 ml of water, collected and dried to give 27.7 gms (92.4 percent) of the sulfonamide (melting point 115°-117° C).
Reaction SMILES: [CH3:1][CH:2]([CH:12]=[CH2:13])[CH2:3][CH2:4][CH:5]([C:9]([CH3:11])=[CH2:10])C(=O)C.C(=[O:16])C.B(F)(F)F.[CH3:21][CH2:22][O:23][CH2:24][CH3:25]>ClCCCl>[C:22]([O:23][CH:24]([CH2:10][C:9]([CH3:11])=[CH:5][CH2:4][CH2:3][CH:2]([CH3:1])[CH:12]=[CH2:13])[CH3:25])(=[O:16])[CH3:21]
Reactant: CCOCC
Reactant: CC=O
Reactant: C=CC(C)CCC(C(=C)C)C(C)=O
Agent: FB(F)F
Solvent: ClCCCl
Product: C=CC(C)CCC=C(C)CC(C)OC(C)=O
Yield: 846.9 %

Procedure:
Following the general procedure as described in Example 1, 6-methyl-3-(prop-1-en-2-yl)oct-7-en-2-one (1.80 g, 10 mmol), acetaldehyde (0.53 g, 12 mmol) and boron trifluoride etherate (0.14 g, 1.0 mmol) in 1,2-dichloroethane (10 mL) were reacted to give the title product as a colorless liquid (1.90 g, 85% yield). Mixture of 2 isomers in a ratio 1:5.
Reaction SMILES: [CH3:1][C:2]1[N:7]=[CH:6][N:5]=[C:4](OS(C2C=CC(C)=CC=2)(=O)=O)[CH:3]=1.[CH2:19]([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH2:20][CH2:21][C:22]#[CH:23]>CCCCCCC.CCOC(C)=O>[CH3:1][C:2]1[CH:3]=[C:4]([C:23]#[C:22][CH2:21][CH2:20][CH2:19][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:5]=[CH:6][N:7]=1
Reactant: Cc1ccc(S(=O)(=O)Oc2cc(C)ncn2)cc1
Reactant: C#CCCCc1ccccc1
Solvent: CCCCCCC
Solvent: CCOC(C)=O
Product: Cc1cc(C#CCCCc2ccccc2)ncn1

Procedure:
This product was prepared from toluene-4-sulfonic acid 6-methyl-pyrimidin-4-yl ester and pent-4-ynyl-benzene following the general procedure for the Sonogashira cross-coupling reaction described above. Chromatography eluent: heptane/EtOAc 8:2; yield (36.6 mg, 31%); 1H NMR δ (CDCl3): 9.01 (s, 1H), 7.31-7.25 (m, 2H), 7.22-7.16 (m, 4H), 2.78 (t, J=7.18 Hz, 2H), 2.51 (s, 3H), 2.41 (t, J=7.17 Hz, 2H), 1.93 (p, J=7.22 Hz, 2H); LCMS m/z: 236.
Reaction SMILES: [CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:9]([C:11]#[N:12])[K].[Br:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18]Br)=[C:16]([F:22])[CH:15]=1>CN(C=O)C>[Br:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18][NH:12][C:11](=[O:9])[O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[C:16]([F:22])[CH:15]=1
Reactant: N#CO[K]
Reactant: Fc1cc(Br)ccc1CBr
Reactant: OCc1ccccc1
Solvent: CN(C)C=O
Product: O=C(NCc1ccc(Br)cc1F)OCc1ccccc1
Temperature: 110 °C

Procedure:
Anhydrous and amine-free DMF (180 ml) and benzyl alcohol (28 ml) and KOCN (0.247 mol, 20 g) are charged into a 500 ml 2-neck round bottom flask having a reflux condenser and drying tube. A solution of 4-bromo-2-fluorobenzyl bromide (0.075 mol, 20 g) in DMF (20 ml) is added rapidly (in the course of 1 min) at room temperature to the stirred reaction mixture by means of a dropping funnel. The resulting suspension is subsequently heated with stirring to approximately 110° C. and further stirred at this temperature for approximately 1.5 h. The mixture is then cooled to room temperature. The salt present in the reaction mixture is filtered off by suction via a frit. The solvent and excess benzyl alcohol are removed from the filtrate in vacuo. The light yellow oily residue is cooled with ice for crystallization. The bright crystalline mass produced is washed with water, filtered and dried. Yield: 23.2 g (:91.5% of theory) M.p.: 82°-84° C. GC/MS: M+ =337, IR in KBr [cm-1 ]: 3342 (m) N--H, 1689 (s) C=O, 1535 (m) NH--C, 1276 (m) C--O--C
Reaction SMILES: O[CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[CH2:8][C@@H:7]([NH:12][S:13]([CH:16]([CH3:18])[CH3:17])(=[O:15])=[O:14])[CH2:6]2.S(Cl)(Cl)=O.[F:23][C:24]([F:35])([F:34])[C:25]1[C:29]([C:30]([OH:33])([CH3:32])[CH3:31])=[CH:28][NH:27][N:26]=1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[OH:33][C:30]([C:29]1[C:25]([C:24]([F:35])([F:34])[F:23])=[N:26][N:27]([CH2:2][C:3]2[CH:4]=[C:5]3[C:9](=[CH:10][CH:11]=2)[CH2:8][C@@H:7]([NH:12][S:13]([CH:16]([CH3:18])[CH3:17])(=[O:15])=[O:14])[CH2:6]3)[CH:28]=1)([CH3:32])[CH3:31]
Reactant: CC(C)(O)c1c[nH]nc1C(F)(F)F
Reactant: CC(C)S(=O)(=O)N[C@@H]1Cc2ccc(CO)cc2C1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: O=S(Cl)Cl
Product: CC(C)S(=O)(=O)N[C@@H]1Cc2ccc(Cn3cc(C(C)(C)O)c(C(F)(F)F)n3)cc2C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 20 %

Procedure:
(R)—N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (30 mg, 0.11 mmol) was dissolved in DCM (5 mL) and thionyl chloride (66 mg, 0.57 mmol) was added. The reaction mixture was stirred at room temperature for 1 h before being concentrated to dryness. The whole was dissolved in DMF (2 mL) and 2-(3-(trifluoromethyl)-1H-pyrazol-4-yl)propan-2-ol (21.6 mg, 0.11 mmol) was added followed by potassium carbonate (30.8 mg, 0.22 mmol). The reaction mixture was stirred at room temperature overnight before being quenched with water (2 mL) and the organics extracted with EtOAc (3×5 mL). The combined organics were washed with brine, dried (MgSO4) and concentrated under reduced pressure. Purification by preparative basic HPLC gave (R)—N-(5-((4-(2-hydroxypropan-2-yl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (9.6 mg, 0.022 mmol, 19.4%). MS (ESI): m/z [M+H]+ 446.5
Reaction SMILES: CO[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=[C:11]([C:19]([OH:21])=[O:20])[CH:10]=2)=[CH:5][CH:4]=1.CC1C=C(C2C=CC=C([N+:39]([O-:41])=[O:40])C=2)C2C(=CC=CC=2)N=1.[Se](=O)=O.OO>>[N+:39]([C:4]1[CH:5]=[C:6]([C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[N:12]=[C:11]([C:19]([OH:21])=[O:20])[CH:10]=2)[CH:7]=[CH:8][CH:3]=1)([O-:41])=[O:40]
Reactant: COc1ccc(-c2cc(C(=O)O)nc3ccccc23)cc1
Reactant: Cc1cc(-c2cccc([N+](=O)[O-])c2)c2ccccc2n1
Agent: O=[Se]=O
Agent: OO
Product: O=C(O)c1cc(-c2cccc([N+](=O)[O-])c2)c2ccccc2n1

Procedure:
4-(3-nitro phenyl) quinoline 2-carboxylic acid is prepared by analogy as 4-(4-methoxy phenyl) quinoline 2-carboxylic acid described in Example 36 starting from 2-methyl 4-(3-nitro phenyl) quinoline (2.46 10-2 mole), 2.73 g of selenium dioxide and 20.9 ml H2O2 110 vol.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[OH:11][CH:12]1[CH2:19][CH2:18][CH:17]2[CH2:20][CH:13]1[CH2:14][N:15]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:16]2.C(N(CC)CC)C>ClCCl>[O:11]=[C:12]1[CH2:19][CH2:18][CH:17]2[CH2:20][CH:13]1[CH2:14][N:15]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:16]2
Reactant: CCOC(=O)N1CC2CCC(O)C(C2)C1
Agent: O=C(Cl)C(=O)Cl
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)N1CC2CCC(=O)C(C2)C1
Temperature: -10 °C
Reaction time: 0.17 h
Yield: 47.3 %

Procedure:
A solution of oxalyl chloride (1.31 mL, 15 mmol) in 50 mL of dichloromethane was cooled in a dry ice-acetone bath, and DMSO (1.4 mL, 20 mmol) was added drop-wise over 5 min. After 10 min, ethyl 6-hydroxy-3-azabicyclo[3.3.1]nonane-3-carboxylate (2.2 g, 10 mmol) in 10 mL dichloromethane was added over 5 min. The mixture was stirred for 20 min, and then triethylamine (6.3 mL, 45 mmol) was added slowly. The mixture was stirred for 1.5 h, gradually warming to −10° C. The reaction was quenched by addition of water (25 mL). The organic layer was separated, washed with brine (25 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a yellow oil. This was chromatographed on a silica gel column, with 2% methanol in dichloromethane, to give the desired ketone (1.0 g, 45%). The chromatography also provided a sample of the isomeric ketone, ethyl 7-oxo-3-azabicyclo[3.3.1]nonane-3-carboxylate, and some un-reacted alcohol starting material.
Reaction SMILES: [Br:1][C:2]1[C:12]2[CH2:11][CH2:10][NH:9][CH2:8][CH:7]([C:13]3[CH:18]=[CH:17][C:16]([O:19]C)=[CH:15][CH:14]=3)[C:6]=2[CH:5]=[C:4]([O:21]C)[C:3]=1[O:23]C.B(Br)(Br)Br>>[BrH:1].[Br:1][C:2]1[C:12]2[CH2:11][CH2:10][NH:9][CH2:8][CH:7]([C:13]3[CH:14]=[CH:15][C:16]([OH:19])=[CH:17][CH:18]=3)[C:6]=2[CH:5]=[C:4]([OH:21])[C:3]=1[OH:23]
Reactant: COc1ccc(C2CNCCc3c2cc(OC)c(OC)c3Br)cc1
Agent: BrB(Br)Br
Product: Br
Product: Oc1ccc(C2CNCCc3c2cc(O)c(O)c3Br)cc1

Procedure:
Substituting a stoichiometric quantity of 2-fluoro-3,4-dimethoxyphenethylamine in the synthetic procedure of Example 1 gave 6-fluoro-7,8-dimethoxy-1-(1-methoxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine as a yellow oil. Hydrolysis with boron tribromide gave 6-fluoro-7,8-dihydroxy-1-(p-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide, m.p. 227° (dec.). Substituting appropriate bromo starting material in the methods described herein gave 6-bromo-7,8-dimethoxy-1-(p-methoxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine then hydrolysis with boron tribromide gave 6-bromo-7,8-dihydroxy-1-(p-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide, m.p. 254° (dec.).
Reaction SMILES: [CH:1]1([C:4]2[S:8][C:7]([N:9]3[CH:14]([OH:15])[CH2:13][CH2:12][N:11]([CH3:16])[C:10]3=[O:17])=[N:6][N:5]=2)[CH2:3][CH2:2]1.C(N(CC)CC)C.[Cl:25][CH2:26][C:27](Cl)=[O:28]>C1C=CC=CC=1>[CH:1]1([C:4]2[S:8][C:7]([N:9]3[CH:14]([O:15][C:27](=[O:28])[CH2:26][Cl:25])[CH2:13][CH2:12][N:11]([CH3:16])[C:10]3=[O:17])=[N:6][N:5]=2)[CH2:2][CH2:3]1
Reactant: CN1CCC(O)N(c2nnc(C3CC3)s2)C1=O
Reactant: O=C(Cl)CCl
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: CN1CCC(OC(=O)CCl)N(c2nnc(C3CC3)s2)C1=O

Procedure:
Tetrahydro-1-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-hydroxy-2(1H)-pyrimidinone (0.05 mole), triethylamine (0.06 mole) and benzene (50 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. Chloroacetyl chloride (0.05 mole) is then added dropwise with stirring. After the addition is completed, the reaction mixture is heated at reflux with continued stirring for a period of about 30 minutes. After this time the reaction mixture is filtered and the filtrate is stripped of solvent under reduced pressure to yield the desired product tetrahydro-1-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-3-methyl-6-chloroacetyloxy-2(1H)-pyrimidinone as the residue.
Reaction SMILES: [NH2:1][CH:2]1[CH2:8][CH2:7][CH2:6][CH:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:4]([CH2:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:3]1=[O:23].O=[C:25]([CH2:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:26]([O:28][CH2:29][CH3:30])=[O:27].C(O)(=O)C>C(O)C>[C:19]([O:18][C:16]([CH2:15][N:4]1[CH:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:6][CH2:7][CH2:8][CH:2]([NH:1][CH:25]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:31][CH2:32][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[C:3]1=[O:23])=[O:17])([CH3:20])([CH3:22])[CH3:21]
Reactant: CC(C)(C)OC(=O)CN1C(=O)C(N)CCCC1c1ccccc1
Reactant: CCOC(=O)C(=O)CCc1ccccc1
Solvent: CC(=O)O
Solvent: CCO
Product: CCOC(=O)C(CCc1ccccc1)NC1CCCC(c2ccccc2)N(CC(=O)OC(C)(C)C)C1=O

Procedure:
A solution of 3.8 g of the amine from Step D, 3.7 g ethyl 2-oxo-4-phenylbutyrate, and 0.68 ml acetic acid in 50 ml ethanol was hydrogenated and the isomers separated by chromatography on silica gel using 1:1 ethylacetate:hexane to afford 1-t-butoxycarbonylmethyl-3-(1-ethoxycarbonyl-3-phenylpropyl)amino-7-phenylperhydroazepin-2-one:
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5](Br)=[C:6]2[C:10]=1[C:9](=[O:11])[NH:8][CH2:7]2.[C:13](=[O:16])([O-])[O-].[K+].[K+].[OH2:19]>>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:2]2[CH:3]=[CH:4][C:5]([OH:19])=[C:6]([O:16][CH3:13])[CH:10]=2)=[C:6]2[C:10]=1[C:9](=[O:11])[NH:8][CH2:7]2
Reactant: Nc1ccc(Br)c2c1C(=O)NC2
Reactant: O=C([O-])[O-]
Reactant: O
Agent: [K+]
Product: COc1cc(-c2ccc(N)c3c2CNC3=O)ccc1O
Temperature: 90 °C
Reaction time: 4.3 h
Yield: 94 %

Procedure:
7-Amino-4-bromoisoindolinone (150 mg, 0.661 mmol) was dissolved in dimethoxythane (10.5 mL), and the solution was added with 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboran-2-yl)phenol (331 mg, 1.32 mmol), [bis(diphenylphosphino)ferrocene]dichloropalladium (43.2 mg, 0.0529 mmol) and potassium carbonate (456 mg, 3.31 mmol), and stirred at 90° C. for 4.3 hours under argon atmosphere. The reaction mixture was added with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by preparative thin-layer chromatography (chloroform/acetonitrile=4/1, chloroform/methanol=10/1) to obtain 7-amino-4-(4-hydroxy-3-methoxyphenyl)isoindolinone (169 mg, yield 94%).
Reaction SMILES: [C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[C:7](O)(=O)[C:8](O)=O.CN(CCC1C=CC=C(C)N=1)CCC([C:19]1[CH:24]=[CH:23][C:22]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])=[CH:21][CH:20]=1)=O.C(O)(=O)C(O)=O.C(O)(=O)C(O)=O.[CH2:51]([N:53]([CH2:70][CH2:71][C:72]1[CH:77]=[CH:76][CH:75]=C(C)[N:73]=1)CCCC(C1C=CC(NS(C)(=O)=O)=CC=1)=O)C.C(O)(=O)C(O)=O.C(O)(=O)C(O)=O.CS(N)(=O)=O>>[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[CH3:51][N:53]([CH2:70][CH2:71][C:72]1[CH:77]=[CH:76][CH:75]=[C:7]([CH3:8])[N:73]=1)[C:19]1[CH:20]=[CH:21][C:22]([NH:25][S:26]([CH3:29])(=[O:27])=[O:28])=[C:23]([C:1](=[O:6])[CH3:2])[CH:24]=1
Reactant: Cc1cccc(CCN(C)CCC(=O)c2ccc(NS(C)(=O)=O)cc2)n1
Reactant: CCN(CCCC(=O)c1ccc(NS(C)(=O)=O)cc1)CCc1cccc(C)n1
Agent: CS(N)(=O)=O
Agent: O=C(O)C(=O)O
Product: CC(=O)c1cc(N(C)CCc2cccc(C)n2)ccc1NS(C)(=O)=O

Procedure:
##STR27## Compound B: Compound prepared in Example 2: N-[4-[3-{N-methyl-(6-methyl-2-pyridyl)-ethylamino}propionyl]phenyl]methanesulfonamide dioxalate: ##STR28## Compound C; Compound prepared in Example 4: N-[4-[4-{N-methyl-2-(6-methyl-2-pyridyl)-ethylamino}butyrul]phenyl]methanesulfonamide dioxalate: ##STR29## Compound D: Compound prepared in Example 5: N-[4-[4-{N-ethyl-2-(6-methyl-2-pyridyl)-ethylamino}butyryl]phenyl]methanesulfonamide dioxalate: ##STR30## Compound E: Compound prepared in Example 6: N-[4-[5-{6-methyl-2-pyridyl)ethylamino}valeryl]-phenyl]methanesulfonamide dioxalate: ##STR31##
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:16]#[N:17])([CH2:14][OH:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:18][S:19](Cl)(=[O:21])=[O:20]>O1CCCC1.C(N(CC)CC)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:16]#[N:17])([CH2:14][O:15][S:19]([CH3:18])(=[O:21])=[O:20])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)N1CCC(C#N)(CO)CC1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(C#N)(COS(C)(=O)=O)CC1
Temperature: 0 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
After dissolving 537 mg of 1-(tert-butoxycarbonyl)-4-cyano-4-(hydroxymethyl)piperidine in 100 ml of tetrahydrofuran, 0.4 ml of triethylamine was added and the solution was cooled to 0° C. 0.2 ml of methanesulfonyl chloride was added and the mixture was stirred overnight at room temperature. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. After adding water to the residue, extraction was performed with ethyl acetate. The organic layer was washed with water and then dried over magnesium sulfate. The solvent was distilled off under reduced pressure to obtain the title compound (799 mg, 100% yield).
Reaction SMILES: [C:1]([C:3]1[CH:4]=[N:5][N:6]2[C:11]([C:12]([F:15])([F:14])[F:13])=[CH:10][C:9]([C:16]3[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=3)=[N:8][C:7]=12)#[CH:2].[NH2:26][C:27]1[N:32]=[CH:31][C:30](Br)=[CH:29][N:28]=1>>[F:15][C:12]([F:14])([F:13])[C:11]1[N:6]2[N:5]=[CH:4][C:3]([C:1]#[C:2][C:30]3[CH:29]=[N:28][C:27]([NH2:26])=[N:32][CH:31]=3)=[C:7]2[N:8]=[C:9]([C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=2)[CH:10]=1
Reactant: Nc1ncc(Br)cn1
Reactant: C#Cc1cnn2c(C(F)(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12
Product: Nc1ncc(C#Cc2cnn3c(C(F)(F)F)cc(-c4ccc(C(F)(F)F)cc4)nc23)cn1

Procedure:
The title compound was prepared from 3-ethynyl-7-trifluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (example C.1) (355 g, 1.0 mmol) and commercially available 2-amino-5-bromopyrimidine (226 mg, 1.3 mmol) according to general procedure II. Obtained as a brown solid (60 mg, 14%). MS (ISP) 449.2 [(M+H)+]; mp 255–256° C.
Reaction SMILES: [C:1]1([C:7]2[N:11]([CH3:12])[N:10]=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.CS(N)(=O)=[O:15].C(O)(C)(C)C.[OH2:23]>>[CH3:12][N:11]1[C:7]([C@:1]2([OH:15])[CH2:6][CH2:5][CH2:4][CH2:3][C@H:2]2[OH:23])=[CH:8][CH:9]=[N:10]1
Reactant: O
Reactant: Cn1nccc1C1=CCCCC1
Reactant: CS(N)(=O)=O
Solvent: CC(C)(C)O
Product: Cn1nccc1[C@]1(O)CCCC[C@H]1O
Yield: 99 %

Procedure:
The reaction and aftertreatment were conducted in the same manner as in Example 102a by using the 5-(cyclohex-1-en-1-yl)-1-methyl-1H-pyrazole (1.00 g, 6.16 mmol) prepared in Example 123b, methanesulfonamide (586 mg, 6.16 mmol), t-butanol (10 mL), water (10 mL) and AD-mixβ (Sigma-Aldrich Corp.; 8.67 g), to yield the title compound (1.21 g, 99%) as a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[CH:18][CH:17]=[C:16]([Si:20]([CH3:23])([CH3:22])[CH3:21])[C:3]=1[C:4]([N:6](CC)[CH:7](OC)[C:8](C)(C)C)=[O:5].CN(CCN(C)C)C.[Li]C(CC)C.C1CCCCC1.[Br:43]CCBr>C1COCC1.CC(C)=O.Cl>[Br:43][C:19]1[C:2]([Cl:1])=[C:3]([C:16]([Si:20]([CH3:23])([CH3:22])[CH3:21])=[CH:17][CH:18]=1)[C:4]([NH:6][CH2:7][CH3:8])=[O:5]
Reactant: CCN(C(=O)c1c(Cl)cccc1[Si](C)(C)C)C(OC)C(C)(C)C
Reactant: BrCCBr
Agent: CN(C)CCN(C)C
Agent: Cl
Agent: [Li]C(C)CC
Solvent: C1CCOC1
Solvent: C1CCCCC1
Solvent: CC(C)=O
Product: CCNC(=O)c1c([Si](C)(C)C)ccc(Br)c1Cl
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
To a solution of the compound of Example 201 (0.79 g, 2.2 mmol) and TMEDA (0.44 mL, 2.9 mmol) in THF (20 mL) at -78° C. was added a solution of 0.86 M s-BuLi in cyclohexane (3.3 mL, 2.9 mmol). The reaction was stirred at -78° C. for 30 min and 1,2-dibromoethane (0.26 mL, 3.0 mmol) was added. The reaction was stirred for 15 min at -78° C. and was quenched with sat NaHCO3. The mixture was extracted with ether, washed with brine, dried (MgSO4) and concentrated to afford a yellow oil. This oil was dissolved in a mixture of acetone (30 mL) and 6 N HCl (15 mL) and was stirred overnight. The mixture was concentrated, extracted with ether, the organic layers washed with brine, dried (MgSO4) and concentrated to afford the title compound as a clear oil. The crude product was purified by RC (ethyl acetate/hexanes) and was recrystallized from pentane (-78° C.) to afford 76 mg of a white solid (10% yield). m.p. 105°-106° C.
Reaction SMILES: Cl[C@@H:2]1[C@H:19]2[O:20][C@:18]32[C@:13]([CH3:28])([CH2:14][CH2:15][C@H:16]([O:21][C:22](=[O:27])[C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:17]3)[C@@H:12]2[C@@H:3]1[C@H:4]1[C@@:8]([CH2:10][CH2:11]2)([CH3:9])[C:7](=[O:29])[C@H:6]2[CH2:30][C@@H:5]12>C(O)(=O)C.O1CCCC1.[Zn]>[OH:20][C@@:18]12[CH2:17][C@@H:16]([O:21][C:22](=[O:27])[C:23]([CH3:24])([CH3:25])[CH3:26])[CH2:15][CH2:14][C@:13]1([CH3:28])[C@@H:12]1[C@H:3]([C@H:4]3[C@@:8]([CH2:10][CH2:11]1)([CH3:9])[C:7](=[O:29])[C@H:6]1[CH2:30][C@@H:5]31)[CH:2]=[CH:19]2
Reactant: CC(C)(C)C(=O)O[C@H]1CC[C@]2(C)[C@H]3CC[C@]4(C)C(=O)[C@H]5C[C@H]5[C@H]4[C@@H]3[C@H](Cl)[C@H]3O[C@]32C1
Agent: [Zn]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CC(C)(C)C(=O)O[C@H]1CC[C@]2(C)[C@H]3CC[C@]4(C)C(=O)[C@H]5C[C@H]5[C@H]4[C@@H]3C=C[C@]2(O)C1
Reaction time: 1 h
Yield: 74.6 %

Procedure:
A solution of 196 g of 7α-chloro-5,6β-epoxy-15β,16β-methylene-3β-pivaloyloxy-5β-androstan-17-one in 500 ml of acetic acid and 800 ml of tetrahydrofuran is combined at 70° C. with 392 g of zinc dust in two portions at an interval of 30 minutes, and stirred for one hour at this temperature. After cooling, the zinc is filtered off over "Celite" and washed with 5 l of methylene chloride. The combined filtrates are mixed with 1.5 l of water and neutralized under agitation by the addition of solid sodium bicarbonate. The organic phase is then washed with water, dried over sodium sulfate, and concentrated under vacuum. By trituration of the thus-obtained solid with ethyl acetate, 134.7 g of 5-hydroxy-15β,16β-methylene-3β-pivaloyloxy-5β-androst-6-en-17-one is produced, mp 243° C.
Reaction SMILES: [CH:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[CH:5][CH:4]=1)=[CH2:2].[Ag:12]=O>C(#N)C>[CH:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([O-:9])=[O:8])=[CH:5][CH:4]=1)=[CH2:2].[Ag+:12]
Reactant: C=Cc1ccc(C(=O)O)cc1
Reactant: O=[Ag]
Solvent: CC#N
Product: C=Cc1ccc(C(=O)[O-])cc1
Product: [Ag+]
Temperature: 23 °C
Reaction time: 0.5 h

Procedure:
A mixture of 3.08 parts of 4-vinylbenzoic acid and 15.00 parts of acetonitrile was stirred at 23° C. for 30 minutes. To the resultant mixture, 2.32 parts of silver oxide was added. The obtained mixture was stirred at 23° C. for 4 hours, and then, filtrated. The obtained solid was mixed with 10 parts of tert-butyl methyl ether and the resultant mixture was stirred at 23° C. for 30 minutes. The mixture was filtrated and the obtained solid was dried to obtain 4.34 parts of silver 4-vinylbenzoate.