Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]3[N:15]4[CH2:16][CH2:17][S:18][C:19]([CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])([CH3:21])[CH2:20][C:14]4=[N:13][N:12]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH:31]([N:34]1[CH:38]=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:36]=[N:35]1)([CH3:33])[CH3:32].C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.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>[Si:24]([O:23][CH2:22][C:19]1([CH3:21])[S:18][CH2:17][CH2:16][N:15]2[C:11]([C:8]3([C:5]4[CH:6]=[CH:7][C:2]([C:37]5[CH:36]=[N:35][N:34]([CH:31]([CH3:33])[CH3:32])[CH:38]=5)=[CH:3][CH:4]=4)[CH2:10][CH2:9]3)=[N:12][N:13]=[C:14]2[CH2:20]1)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25]
Reactant: CC(C)n1cc(B2OC(C)(C)C(C)(C)O2)cn1
Reactant: CC1(CO[Si](C)(C)C(C)(C)C)Cc2nnc(C3(c4ccc(Br)cc4)CC3)n2CCS1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: COCCOC
Solvent: O
Product: CC(C)n1cc(-c2ccc(C3(c4nnc5n4CCSC(C)(CO[Si](C)(C)C(C)(C)C)C5)CC3)cc2)cn1
Temperature: 25 °C
Yield: 68.4 %

Procedure:
A solution of the compound (300 mg, 0.59 mmol) obtained in Example 16-4), 1-isopropylpyrazole-4-boronic acid pinacol ester (153 mg, 0.65 mmol), tetrakis(triphenylphosphine)palladium(0) (68 mg, 0.06 mmol), and potassium carbonate (163 mg, 1.18 mmol) in 1,2-dimethoxyethane (3 mL) and water (1.5 mL) was stirred at 120° C. for 1 h under microwave irradiation. The reaction mixture was cooled to room temperature, water (3 mL) was added to the reaction mixture, the mixture was extracted with ethyl acetate, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by silica gel chromatography (ethyl acetate:methanol=70:30) to obtain the title compound (217 mg, 68%) in an orange oily form.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:13]2[C:21]3[C:16](=[C:17]([CH2:22][S:23][CH3:24])[CH:18]=[CH:19][CH:20]=3)[NH:15][CH:14]=2)([CH:10]2[CH2:12][CH2:11]2)[CH3:9])=[C:4]([F:25])[CH:3]=1.ClCCl.ClC1C=CC=C(C(OO)=[O:37])C=1>CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:13]2[C:21]3[C:16](=[C:17]([CH2:22][S:23]([CH3:24])=[O:37])[CH:18]=[CH:19][CH:20]=3)[NH:15][CH:14]=2)([CH:10]2[CH2:12][CH2:11]2)[CH3:9])=[C:4]([F:25])[CH:3]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CSCc1cccc2c(C(C)(c3ccc(Cl)cc3F)C3CC3)c[nH]c12
Solvent: CO
Solvent: ClCCl
Product: CS(=O)Cc1cccc2c(C(C)(c3ccc(Cl)cc3F)C3CC3)c[nH]c12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
100 mg (0.27 mmol) of the compound from Example 97 were introduced into 18 ml of dichloromethane at 0° C., 66 mg (0.27 mmol) of 70% pure meta-chloroperbenzoic acid were added, and the mixture was stirred at RT for 2 h. 2 ml of methanol were added, and the solvents were removed in vacuo. The residue was taken up in ethyl acetate and washed with water, saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution. The solvents were removed in vacuo. The crude product was purified by preparative HPLC (mobile phase: acetonitrile/water gradient) to result in 86 mg (83% of theory) of the title compound as mixture of diastereomers.
Reaction SMILES: [CH3:1][N:2]([S:4]([CH2:7][Li])(=[O:6])=[O:5])[CH3:3].[CH2:9]([Sn:13](Cl)([CH2:18][CH2:19][CH2:20][CH3:21])[CH2:14][CH2:15][CH2:16][CH3:17])[CH2:10][CH2:11][CH3:12].[Cl-].[NH4+]>CCCCCC.C1COCC1.C1COCC1>[CH3:1][N:2]([S:4]([CH2:7][Sn:13]([CH2:14][CH2:15][CH2:16][CH3:17])([CH2:18][CH2:19][CH2:20][CH3:21])[CH2:9][CH2:10][CH2:11][CH3:12])(=[O:6])=[O:5])[CH3:3]
Reactant: [Li]CS(=O)(=O)N(C)C
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCCC[Sn](CCCC)(CCCC)CS(=O)(=O)N(C)C
Temperature: 20 °C
Reaction time: 2 h

Procedure:
Employing the apparatus and procedure of Example I, 100 ml. of an approximately one-molar solution of (N,N-dimethylaminosulfonylmethyl)lithium in hexane-THF solvent was added slowly over a period of 30 minutes to 0.1 mole of tri-n-butyltin chloride dissolved in THF. The temperature at addition was -60° C provided by a dry ice-acetone bath and rose through the addition period to 0° C. Following the complete addition, the reaction mixture was stirred for 2 hours at room temperature (20° C) and hydrolyzed by pouring into an aqueous one-molar ammonium chloride solution. Extraction from the hydrolyzate with ether solvent and purification by vacuum distillation yielded the desired compound, (N,N-dimethylaminosulfonylmethyl)tributyltin. The product, a pale-yellow liquid, had a boiling point of from 158°-160° C/0.1 mm. Hg. Analysis gave 43.8% Carbon and 8.5% Hydrogen compared to the calculated values, respectively, of 43.7% and 8.5%. The assigned structure was confirmed by infrared and proton nuclear magnetic resonance spectral analyses.
Reaction SMILES: [NH2:1][NH2:2].COC(=O)[CH:6]([C:14]1[CH:19]=[N:18][C:17]([C:20](=O)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[Cl:27])=[C:16](Cl)[N:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[F:13].[OH-].[Li+].Cl>C1COCC1.O>[Cl:27][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[C:20]1[C:17]2[C:16](=[N:15][C:14]([CH2:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[F:13])=[CH:19][N:18]=2)[NH:2][N:1]=1
Reactant: NN
Reactant: COC(=O)C(c1cnc(C(=O)c2ccccc2Cl)c(Cl)n1)c1ccccc1F
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Fc1ccccc1Cc1cnc2c(-c3ccccc3Cl)n[nH]c2n1
Temperature: 25 °C
Yield: 31.8 %

Procedure:
Hydrazine (54 mg, 1.7 mmol) was added to a solution of [6-Chloro-5-(2-chloro-benzoyl)-pyrazin-2-yl]-(2-fluoro-phenyl)-acetic acid methyl ester (0.59 g, 1.4 mmol) in 50 mL THF at 0° C., and the reaction mixture was stirred and allowed to warm to room temperature. Lithium hydroxide (27 mg, 5.0 mmol) was added, and the reaction mixture was stirred for 64 hours at room temperature. Concentrated aqueous HCl (1 ml) was then added, and the reaction mixture was stirred for one hour at room temperature. The reaction mixture was poured into water, extracted with diethyl ether, and the combined organic phases were dried over MgSO4, filtered, and evaporated under reduced pressure. The residue was purified via chromatography using 5% ethyl acetate in hexanes as the eluent to afford 0.151 g of 3-(2-Chloro-phenyl)-6-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyrazine. Mass Spec. M+H=340.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH:10]([OH:13])[CH2:11][OH:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:14](Cl)(=[O:26])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]>>[C:14]([O:12][CH2:11][CH:10]([CH2:9][O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[O:13][C:14](=[O:26])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])(=[O:26])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]
Reactant: OCC(O)COCc1ccccc1
Reactant: CCCCCCCCCCCC(=O)Cl
Product: CCCCCCCCCCCC(=O)OCC(COCc1ccccc1)OC(=O)CCCCCCCCCCC
Yield: 76.2 %

Procedure:
3-O-Benzylglycerol (7 g) is reacted with 18.5 g of lauroyl chloride in the same manner as in Starting Material Synthesis 2. Recrystallization of the crude crystals from ethanol gives 16 g of white crystals. Melting point: 30°-31° C.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][CH2:11][C:12]1[C:13](=O)[NH:14][C:15]([CH3:20])=[C:16]([CH2:18][CH3:19])[CH:17]=1.COC1C=CC(P2(=S)SP(=S)(C3C=CC(OC)=CC=3)[S:31]2)=CC=1>C1(C)C=CC=CC=1>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][CH2:11][C:12]1[C:13](=[S:31])[NH:14][C:15]([CH3:20])=[C:16]([CH2:18][CH3:19])[CH:17]=1
Reactant: CCc1cc(CCc2nc3ccccc3o2)c(=O)[nH]c1C
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: Cc1ccccc1
Product: CCc1cc(CCc2nc3ccccc3o2)c(=S)[nH]c1C
Yield: 24.7 %

Procedure:
A mixture of 3-[2-(benzoxazol-2-yl)-ethyl]-5-ethyl-6-methyl pyridin-2(1H)-one (150 mg, 0.53 mmol) and 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide (Lawesson's Reagent) (485 mg, 1.2 mmol) in dry toluene (4 mL) was refluxed for 6-10 hours. The solvent was evaporated and the reaction residue was flash chromatographed on silica gel eluting with 0.5% methanol/chloroform. The appropriate fractions were combined and crystallized from ethyl acetate to yield 80 mg of slightly impure product. This material was re-chromatographed on silica gel eluting with chloroform. The appropriate fractions were combined, the solvent evaporated, and the residue recrystallized from boiling diethyl ether, after addition of sufficient methylene chloride to effect complete dissolution, to yield 39 mg (24%) of pure product, m.p. 199°-201° C.
Reaction SMILES: [CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[C:5]([Cl:9])[NH:4][C:3]1=[O:10].Br[CH2:12][C:13]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:14]=1[C:15]#[N:16].C([O-])([O-])=O.[K+].[K+]>CS(C)=O.O>[Cl:9][C:5]1[N:4]([CH2:12][C:13]2[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:14]=2[C:15]#[N:16])[C:3](=[O:10])[N:2]([CH3:1])[C:7](=[O:8])[CH:6]=1
Reactant: N#Cc1ccc(F)cc1CBr
Reactant: Cn1c(=O)cc(Cl)[nH]c1=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: Cn1c(=O)cc(Cl)n(Cc2cc(F)ccc2C#N)c1=O
Temperature: 60 °C
Reaction time: 2 h
Yield: 59.1 %

Procedure:
A mixture of crude 3-methyl-6-chlorouracil (0.6 g, 3.8 mmol), 2-bromomethyl-4-fluorobenzonitrile (0.86 g, 4 mmol) and K2CO3 (0.5 g, 4 mmol) in DMSO (10 mL) was stirred at 60° C. for 2 hours. The reaction was diluted with water and extracted with EtOAc. The organics were dried over MgSO4 and the solvent removed. The residue was purified by column chromatography. 0.66 g of the product was obtained (yield: 60%). 1H-NMR (400 MHz, CDCl3): δ 7.73 (dd, J=7.2, 8.4 Hz, 1H), 7.26 (d, J=4.0 Hz, 1H), 7.11-7.17 (m, 1H), 6.94 (dd, J=2.0, 9.0 Hz, 1H), 6.034 (s, 2H), 3.39 (s, 3H). MS (ES) [m+H] calc'd for C13H9ClFN3O2, 293.68; found 293.68.
Reaction SMILES: [Br:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([C:8]2[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=2[NH:15]C(=O)OC(C)(C)C)=[O:7])=[CH:4][CH:3]=1.Cl.CO>CO>[NH2:15][C:9]1[CH:10]=[CH:11][C:12]([Cl:14])=[CH:13][C:8]=1[C:6]([C:5]1[CH:23]=[CH:24][C:2]([Br:1])=[CH:3][CH:4]=1)=[O:7]
Reactant: CC(C)(C)OC(=O)Nc1ccc(Cl)cc1C(=O)c1ccc(Br)cc1
Agent: Cl
Solvent: CO
Product: Nc1ccc(Cl)cc1C(=O)c1ccc(Br)cc1
Reaction time: 4 h
Yield: 96.6 %

Procedure:
To a solution of tert-butyl [2-(4-bromobenzoyl)-4-chlorophenyl]carbamate (10 g, 25 mmol) in MeOH (50 mL) at 25° C. was added 2 M HCl-MeOH (100 ml), and the reaction mixture stirred for 4 h. The organic layer was evaporated, then the residue was partitioned between CH2Cl2 (300 ml) and water (200 ml). The organic layer was washed with 10% Na2CO3 (to pH=9) and brine, dried over Na2SO4 and evaporated to give 7.5 g (98% yield) (2-amino-5-chlorophenyl)(4-bromophenyl)methanone. To a solution of (2-amino-5-chlorophenyl)(4-bromophenyl)methanone (13 g, 42 mmol) in 500 ml CH2Cl2 was added solid carbonyldiimidazole (15.7 g, 96 mmol) portionwise. The resulting yellow solution was allowed to stir at 40° C. for 16 hrs, concentrated to give a yellow foam. The foam was treated with 30 ml of ether and 20 ml of water with vigorous stirring resulting in a solid precipitate. After filtration, the cake was recrystallized from CH2Cl2/Ether (1:5) to give N-[4-chloro-2-(4-bromobenzoyl)phenyl]-1H-imidazole-1-carboxamide as a yellow solid. 1HNMR: (400 MHz, DMSO-d6) δ 11.05 (s, 1H), 7.69 (d, J=8.4 Hz, 2H), 7.55 (dd, J=8.4, 1.6 Hz, 1H), 7.33 (s, 1H), 6.98˜7.10 (m, 5H), 6.71 (d, J=2.0 Hz, 1H).
Reaction SMILES: [CH3:1][N:2]1[CH:7]2[CH2:8][CH2:9][CH2:10][CH:3]1[CH2:4][NH:5][CH2:6]2.Cl[C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([N+:22]([O-:24])=[O:23])[CH:18]=2)[N:13]=1.C(N(CC)C(C)C)(C)C>O1CCOCC1>[CH3:1][N:2]1[CH:7]2[CH2:8][CH2:9][CH2:10][CH:3]1[CH2:4][N:5]([C:12]1[CH:21]=[CH:20][C:19]3[C:14](=[CH:15][CH:16]=[C:17]([N+:22]([O-:24])=[O:23])[CH:18]=3)[N:13]=1)[CH2:6]2
Reactant: CN1C2CCCC1CNC2
Reactant: O=[N+]([O-])c1ccc2nc(Cl)ccc2c1
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Product: CN1C2CCCC1CN(c1ccc3cc([N+](=O)[O-])ccc3n1)C2
Temperature: 25 °C

Procedure:
A mixture of 9-methyl-3,9-diaza-bicyclo[3.3.1]nonane (0.50 g, 3.56 mmol), 2-chloro-6-nitroquinoline (0.74 g, 3.56 mmol), N,N-diisopropylethylamine (0.92 g, 7.13 mmol) and dioxane (25 ml) was stirred at reflux for 40 h. The mixture was allowed to cool to room temperature. The precipitated product was filtered and was washed with diethylether. The crude product was purified by silica gel column chromatography using a solvent mixture of dichloromethane, methanol and aqueous ammonia (9:1:1%). The pure product was isolated. Yield 300 mg (27%). Mp 166.2° C. LC-ESI-HRMS of [M+H]+ shows 313.1674 Da. Calc. 313.166451 Da, dev. 3 ppm.
Reaction SMILES: I[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]1[CH2:18][C:17]2[C:12](=[C:13]([O:25][CH3:26])[C:14]([O:23][CH3:24])=[C:15]([O:21][CH3:22])[C:16]=2[O:19][CH3:20])[CH2:11]1.[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([OH:34])=[CH:30][CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]2[CH2:18][C:17]3[C:12](=[C:13]([O:25][CH3:26])[C:14]([O:23][CH3:24])=[C:15]([O:21][CH3:22])[C:16]=3[O:19][CH3:20])[CH2:11]2)=[CH:30][CH:29]=1
Reactant: COc1c2c(c(OC)c(OC)c1OC)CC(CCCCCCCCI)C2
Reactant: Oc1ccc(Cl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1c2c(c(OC)c(OC)c1OC)CC(CCCCCCCCOc1ccc(Cl)cc1)C2
Temperature: 25 °C
Reaction time: 12 h
Yield: 93.4 %

Procedure:
The mixture of 2-(8-iodooctyl)-4,5,6,7-tetramethoxyindan (830 mg), 4-chlorophenol (269 mg), and potassium carbonate (481 mg) in DMF (8 ml) was stirred at room temperature for 12 hr. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride and dried. The solvent was removed in vacuo. The residue was purified by alumina column chromatography (hexane to hexane:ethyl acetate=10:1) to yield the entitled compound (776 mg) as crystals.
Reaction SMILES: [OH-].[Na+:2].[O:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[C:10]([NH:17][C:18](=[O:28])[C:19]2[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[CH:21][C:20]=2[OH:27])[CH:9]=1>C(O)C>[O:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[C:8]1[CH:16]=[CH:15][C:11]([C:12]([O-:14])=[O:13])=[C:10]([NH:17][C:18](=[O:28])[C:19]2[CH:24]=[C:23]([O:25][CH3:26])[CH:22]=[CH:21][C:20]=2[OH:27])[CH:9]=1.[Na+:2]
Reactant: COc1ccc(O)c(C(=O)Nc2cc(-c3ccco3)ccc2C(=O)O)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: COc1ccc(O)c(C(=O)Nc2cc(-c3ccco3)ccc2C(=O)[O-])c1
Temperature: 25 °C
Reaction time: 0.58 h

Procedure:
Ethanol (2.5 mL) and a 1 mol/L aqueous solution of sodium hydroxide (0.17 mL) were added to the obtained 4-(furan-2-yl)-2-(2-hydroxy-5-methoxybenzamido)benzoic acid (0.062 g), followed by stirring at room temperature for 35 minutes. The solid substance was collected by filtration to obtain 0.046 g of sodium 4-(furan-2-yl)-2-(2-hydroxy-5-methoxybenzamido)benzoate as a white solid.
Reaction SMILES: [NH2:1][C:2]1[C:11]([O:12][CH3:13])=[C:10]([Cl:14])[CH:9]=[C:8]([Cl:15])[C:3]=1[C:4]([O:6]C)=[O:5].[OH-].[Na+]>CO.O>[NH2:1][C:2]1[C:11]([O:12][CH3:13])=[C:10]([Cl:14])[CH:9]=[C:8]([Cl:15])[C:3]=1[C:4]([OH:6])=[O:5]
Reactant: COC(=O)c1c(Cl)cc(Cl)c(OC)c1N
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: COc1c(Cl)cc(Cl)c(C(=O)O)c1N
Yield: 9.6 %

Procedure:
To a stirred solution of aniline 2-3 (11.5 g, 460 mmol) in methanol (250 mL) and H2O (70 mL) was added 2N NaOH (25 mL). The reaction mixture was heated under reflux for 1 h, more 2N NaOH (25 mL) was added and the mixture was heated under reflux for a further 1 h. The solution was cooled and methanol was removed in vacuo. The mixture was dissolved in H2O and extracted with ethyl acetate. The aqueous layer was acidified to pH 2 with conc. HCl. and then extracted into ethyl acetate (×3). The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated to provide the acid 2-4 as a beige solid (10.4 g, 95% yield). 1H NMR (MeOD, 400 MHz) δ 3.80 (s, 3H), 6.70 (s, 1H).
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][C:5]2([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[S:11][C:10]3[CH:18]=[CH:19][CH:20]=[CH:21][C:9]=3[C:8]2=[O:22])[CH2:4][CH2:3]1>O1CCCC1>[OH:22][CH:8]1[C:5]2([CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=2[S:11][C:10]2[CH:18]=[CH:19][CH:20]=[CH:21][C:9]1=2
Reactant: CN1CCC2(CC1)C(=O)c1ccccc1Sc1ccccc12
Solvent: C1CCOC1
Product: CN1CCC2(CC1)c1ccccc1Sc1ccccc1C2O

Procedure:
A solution of 5.0 g of 10,11-dihydro-1'-methyl-11-oxospiro[dibenz(b,f)thiepin-10,4'-piperidine], free base of Example 8, in 40 ml of tetrahydrofuran is treated according to the procedure of Example 7 to provide 10,11-dihydro-11-hydroxy-1'-methylspiro[dibenz(b,f)thiepin-10,4'-piperidine].
Reaction SMILES: C[O:2][C:3](=[O:24])[C:4](=[O:23])[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:12][C:13]2[CH:22]=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]=2)=[CH:7][CH:6]=1.[OH-].[Na+]>CO.O1CCCC1>[N:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:21]=[CH:22][C:13]=1[CH2:12][O:11][C:8]1[CH:9]=[CH:10][C:5]([C:4](=[O:23])[C:3]([OH:24])=[O:2])=[CH:6][CH:7]=1
Reactant: COC(=O)C(=O)c1ccc(OCc2ccc3ccccc3n2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: O=C(O)C(=O)c1ccc(OCc2ccc3ccccc3n2)cc1
Reaction time: 0.08 h
Yield: 43.7 %

Procedure:
A solution of 4-[(2-quinolinyl)methoxy]-alpha-oxobenzeneacetic acid methyl ester (0.34 g) in methanol (2 mL) and tetrahydrofuran (8 mL) was treated with 1N sodium hydroxide (1.1 mL) and a white precipitate formed. After 5 minutes, the reaction mixture was concentrated and the residue was acidified with excess hydrochloric acid. The residue was triturated with water (25 mL) and dichloromethane-tetrahydrofuran (150 mL, 9:1) and the solids were crystallized twice from dimethylsulfoxide-acetonitrile-water to give 0.142 g of 4-[(2-quinolinyl)methoxy]-alpha-oxo-benzeneacetic acid, mp 225°-228° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([Cl:12])[C:3]=1[C:13]1[NH:14][CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:17]=1.[Br:22]Br.O>C(O)(=O)C>[Br:22][C:15]1[NH:14][C:13]([C:3]2[C:2]([Cl:1])=[CH:7][C:6]([C:8]([F:10])([F:9])[F:11])=[CH:5][C:4]=2[Cl:12])=[N:17][C:16]=1[C:18]([F:21])([F:19])[F:20]
Reactant: FC(F)(F)c1cc(Cl)c(-c2nc(C(F)(F)F)c[nH]2)c(Cl)c1
Reactant: BrBr
Solvent: CC(=O)O
Solvent: O
Product: FC(F)(F)c1cc(Cl)c(-c2nc(C(F)(F)F)c(Br)[nH]2)c(Cl)c1
Yield: 70.1 %

Procedure:
A solution of 2-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylimidazole (0.7 g, 0.002 mol) and bromine (0.32 g, 0.1 ml, 0.002 mol) in glacial acetic acid (5 ml) was stirred and heated at reflux for 2 hours. The cooled suspension was poured into cold water (50 ) and the solid was filtered and washed with water. The solid was dissolved in glacial acetic acid (5 ml) and bromine (0.32 g, 0.1 ml, 0.002 mol) was added. The mixture was stirred and heated at reflux for 2 hours, cooled and poured into cold water (50 ml). The solid was filtered and washed thoroughly with water to give 5-bromo-2-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylimidazole (0.6 g) as a white solid, m.p. 295° C. with decomposition.
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[C@@:37]2([CH3:38])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:36]2[CH2:35][CH2:34][C@@:33]2([CH3:39])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@@H:21]([S:23][C:24](OC2C=CC=CC=2)=O)[CH3:22])[CH2:12][C@@H:11]([OH:40])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].BrC/[CH:43]=[CH:44]\[C:45]([CH2:56][CH3:57])([O:48][Si:49]([CH2:54][CH3:55])([CH2:52][CH3:53])[CH2:50][CH3:51])[CH2:46][CH3:47].O1CCCC1.[OH-].[K+]>CO>[Si:1]([O:8][C@@H:9]1[C@@:37]2([CH3:38])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:36]2[CH2:35][CH2:34][C@@:33]2([CH3:39])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@@H:21]([S:23][CH2:24]/[CH:43]=[CH:44]\[C:45]([CH2:56][CH3:57])([O:48][Si:49]([CH2:52][CH3:53])([CH2:54][CH3:55])[CH2:50][CH3:51])[CH2:46][CH3:47])[CH3:22])[CH2:12][C@@H:11]([OH:40])[CH2:10]1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]
Reactant: CCC(/C=C\CBr)(CC)O[Si](CC)(CC)CC
Reactant: C[C@H](SC(=O)Oc1ccccc1)C1=CC[C@H]2C3=CC=C4C[C@@H](O)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CCC(/C=C\CS[C@@H](C)C1=CC[C@H]2C3=CC=C4C[C@@H](O)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C)(CC)O[Si](CC)(CC)CC
Yield: 59.8 %

Procedure:
Under the same conditions as in Example 3, 1α-(tert-butyldimethylsilyloxy)-3β-hydroxy-20(S)-phenoxycarbonylthio-pregna-5,7,16-triene (33.0 mg, 0.0568 mmol), (Z)-1-bromo-4-ethyl-4-triethylsilyloxy-2-hexene (91.0 mg, 0.284 mmol), tetrahydrofuran (0.5 ml) and 1M KOH solution in methanol (0.5 ml) were reacted and worked up, and then the residue was purified by preparative thin layer chromatography (0.5 mm×1, hexane ethyl acetate=2:1, developed once) to give the title compound as a pale yellow oil (23.8 mg, 60%).
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:12]=2[Cl:18])[CH:5]=[CH:4][N:3]=1.[CH3:19][O:20][CH2:21][CH:22]([NH2:25])[CH2:23][CH3:24]>>[Cl:18][C:12]1[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:11]=1[C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:25][CH:22]([CH2:21][O:20][CH3:19])[CH2:23][CH3:24])[C:7]=1[N+:8]([O-:10])=[O:9]
Reactant: CCC(N)COC
Reactant: O=[N+]([O-])c1c(-c2ccc(Cl)cc2Cl)ccnc1Cl
Product: CCC(COC)Nc1nccc(-c2ccc(Cl)cc2Cl)c1[N+](=O)[O-]
Yield: 85.9 %

Procedure:
2-Chloro-4-(2,4-dichloro-phenyl)-3-nitro-pyridine (0.20 g, 0.66 mmol) and 1-methoxymethyl-propylamine (0.14 g, 1.32 mmol) were treated as in Part D of Example 9 to yield 0.21 g (88%) of [4-(2,4-dichloro-phenyl)-3-nitro-pyridin-2-yl]-(1-methoxymethyl-propyl)-amine: MS (AP) m/z 370.2 [(M+H)+, 97].
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=[CH:14][CH2:15][CH2:16][CH2:17][C:18]#[N:19])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>O1CCCC1.[Pt](=O)=O>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][CH2:16][CH2:17][C:18]#[N:19])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: N#CCCCC=C1CCN(Cc2ccccc2)CC1
Agent: O=[Pt]=O
Solvent: C1CCOC1
Product: N#CCCCCC1CCN(Cc2ccccc2)CC1
Reaction time: 12 h
Yield: 56.4 %

Procedure:
A mixture of 1-benzyl-4-(4-cyanobutylidene)piperidine (8.8 g) and platinum dioxide (1.2 g) in tetrahydrofuran (150 ml) was hydrogenated at atmospheric pressure for 12 hours. After the catalyst was filtered out, the filtrate was evaporated in vacuo. The residue was chromatographed on silica gel eluting with chloroform/methanol (95:5) and the fractions containing the object compound were combined and evaporated to afford 1-benzyl-4-(4-cyanobutyl)piperidine (5.0 g) as an oil.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[C:11](Cl)(=[O:14])[CH:12]=[CH2:13].[Cl-].[Al+3].[Cl-].[Cl-]>>[C:11]([C:7]1[CH:8]=[CH:9][C:10]2[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=2)[CH:6]=1)(=[O:14])[CH:12]=[CH2:13]
Reactant: C=CC(=O)Cl
Reactant: c1ccc2ccccc2c1
Agent: [Al+3]
Agent: [Cl-]
Product: C=CC(=O)c1ccc2ccccc2c1
Yield: 41.2 %

Procedure:
Naphthalene (0.128 g), acryloyl chloride (0.11 g), and aluminium chloride (0.15 g) were treated in the same manner as described in Example 1 to obtain the title compound (75 mg).
Reaction SMILES: C1(C[O:8][C:9]2[CH:21]=[CH:20][C:12]([C:13]([O:15][CH2:16][CH:17]3[CH2:19][CH2:18]3)=[O:14])=[CH:11][CH:10]=2)C=CC=CC=1.[H][H]>[Pd].CC(O)C>[OH:8][C:9]1[CH:10]=[CH:11][C:12]([C:13]([O:15][CH2:16][CH:17]2[CH2:19][CH2:18]2)=[O:14])=[CH:20][CH:21]=1
Reactant: O=C(OCC1CC1)c1ccc(OCc2ccccc2)cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CC(C)O
Product: O=C(OCC1CC1)c1ccc(O)cc1
Yield: 100 %

Procedure:
A mixture of 14 parts of (cyclopropylmethyl) 4-(phenylmethoxy)benzoate and 200 parts of 2-propanol was hydrogenated at normal pressure and at room temperature with 2 parts of palladium-on-charcoal catalyst 10%. After the calculated amount of hydrogen was taken up, the catalyst was filtered off and the filtrate was evaporated, yielding 8.1 parts (100%) of (cyclopropylmethyl) 4-hydroxybenzoate as a residue (int. 4).