Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([NH2:3])[CH3:2].CO.[S:6](Cl)([C:9]1[CH:17]=[CH:16][C:12]([N+:13]([O-:15])=[O:14])=[CH:11][CH:10]=1)(=[O:8])=[O:7]>O>[CH2:1]([NH:3][S:6]([C:9]1[CH:10]=[CH:11][C:12]([N+:13]([O-:15])=[O:14])=[CH:16][CH:17]=1)(=[O:7])=[O:8])[CH3:2]
Reactant: CCN
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)Cl)cc1
Solvent: CO
Solvent: O
Product: CCNS(=O)(=O)c1ccc([N+](=O)[O-])cc1
Temperature: 0 °C
Yield: 79 %

Procedure:
To a 40-mL vial with magnetic stir bar at 25° C. was added the Ethylamine solution (0.91 g, 20 mmol, 1.3 mL, 70% w/v in water, 4.5 eq.) and methanol (5 mL). The reaction vial was cooled to 0° C. The Nosyl chloride (1.0 g, 4.5 mmol, 1 eq.) was added portion-wise keeping the temperature between 0-5° C. and stirring continued ×15 min. after addition was complete. Water (10 mL) was then added. A precipitate began to form immediately. Stirring was continued at 0° C.×30 minutes. The material was collected by filtration, rinsed with water, and dried thoroughly in vacuo to afford 827 mg (79% yield). LCMS (ESI) 231 (M+H); 229 (M−H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:9]2[C:18]([N:19]([CH:21]([CH3:23])[CH3:22])[CH3:20])=[N:17][C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:24]([O:26][CH3:27])=[O:25])[CH:15]=3)[N:10]=2)[CH:5]=[CH:6][C:7]=1[NH2:8].[N:28]([O-])=O.[Na+]>Cl.O>[NH:8]1[C:7]2[CH:6]=[CH:5][C:4]([C:9]3[C:18]([N:19]([CH:21]([CH3:23])[CH3:22])[CH3:20])=[N:17][C:16]4[C:11](=[CH:12][CH:13]=[C:14]([C:24]([O:26][CH3:27])=[O:25])[CH:15]=4)[N:10]=3)=[CH:3][C:2]=2[N:1]=[N:28]1
Reactant: O=N[O-]
Reactant: COC(=O)c1ccc2nc(-c3ccc(N)c(N)c3)c(N(C)C(C)C)nc2c1
Agent: Cl
Agent: [Na+]
Solvent: O
Product: COC(=O)c1ccc2nc(-c3ccc4[nH]nnc4c3)c(N(C)C(C)C)nc2c1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 21.4 %

Procedure:
To a solution of methyl 2-(3,4-diaminophenyl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylate (635 mg, crude) in HCl (1N, 150 mL) was added sodium nitrite (132 mg, 1.91 mmol) in water (1 mL) at 0° C. After stirring for 15 min at 0° C., the reaction mixture was extracted with dichloromethane (3×50 mL), dried over anhydrous sodium sulfate and concentrated under vacuum to give a residue, which was purified via silica gel chromatography (3% methanol in dichloromethane) to afford methyl 2-(1H-benzo[d][1,2,3]triazol-5-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylate as a yellow solid (140 mg).
Reaction SMILES: [C:1]12([CH2:11][O:12][C:13]3[C:39]([Cl:40])=[CH:38][C:16]([C:17]([NH:19][S:20]([N:23]4[CH2:27][CH2:26][C@H:25]([O:28]CC5C=CC(OC)=CC=5)[CH2:24]4)(=[O:22])=[O:21])=[O:18])=[C:15]([F:41])[CH:14]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl>ClCCl.O>[C:1]12([CH2:11][O:12][C:13]3[C:39]([Cl:40])=[CH:38][C:16]([C:17]([NH:19][S:20]([N:23]4[CH2:27][CH2:26][C@H:25]([OH:28])[CH2:24]4)(=[O:22])=[O:21])=[O:18])=[C:15]([F:41])[CH:14]=3)[CH2:8][CH:7]3[CH2:6][CH:5]([CH2:4][CH:3]([CH2:9]3)[CH2:2]1)[CH2:10]2
Reactant: COc1ccc(CO[C@H]2CCN(S(=O)(=O)NC(=O)c3cc(Cl)c(OCC45CC6CC(CC(C6)C4)C5)cc3F)C2)cc1
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: ClCCl
Solvent: O
Product: O=C(NS(=O)(=O)N1CC[C@H](O)C1)c1cc(Cl)c(OCC23CC4CC(CC(C4)C2)C3)cc1F
Reaction time: 16 h
Yield: 58.7 %

Procedure:
A mixture of 4-(adamantan-1-ylmethoxy)-5-chloro-2-fluoro-N-(((S)-3-((4-methoxybenzyl)oxy)pyrrolidin-1-yl)sulfonyl)benzamide (0.17 g, 0.28 mmol) in dichloromethane (18 mL) and water (2 mL) was added 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (0.08 g, 0.36 mmol) at ambient temperature and stirred for 16 h. Water (20 mL) was added and the mixture extracted with ethyl acetate (80 mL×2), the combined organics were washed with brine; dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was filtered through a short silicon gel column, eluted with 5%-60% gradient ethyl acetate in hexanes to give the title compound as colorless solid (0.08 g, 55%): 1H NMR (300 MHz, DMSO-d6) δ 11.73 (s, 1H), 7.70 (d, J=7.5 Hz, 1H), 7.21 (d, J=12.4 Hz, 1H), 5.07 (brs, 1H), 4.32-4.27 (m, 1H), 3.71 (s, 2H), 3.56-3.48 (m, 3H), 3.23-3.19 (m, 1H), 1.99 (s, 3H), 1.93-1.63 (m, 14H); MS (ES+) m/z 487.2, 489.1 (M+1); MS (ES−) m/z 485.3, 487.3 (M−1).
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C@@H:9]([C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[N:19]=3)[N:14]=[CH:13][CH:12]=2)[OH:10])[CH2:4][CH2:3]1.[N:23]1[C:32]2[NH:31][CH2:30][CH2:29][CH2:28][C:27]=2[CH:26]=[CH:25][C:24]=1[CH:33]=O.[O-]S([O-])(=O)=O.[Na+].[Na+].[BH4-].[Na+]>C(Cl)Cl.C(O)C>[CH3:22][O:21][C:18]1[N:19]=[C:20]2[C:15](=[CH:16][CH:17]=1)[N:14]=[CH:13][CH:12]=[C:11]2[C@@H:9]([OH:10])[CH2:8][N:5]1[CH2:6][CH2:7][CH:2]([NH:1][CH2:33][C:24]2[CH:25]=[CH:26][C:27]3[CH2:28][CH2:29][CH2:30][NH:31][C:32]=3[N:23]=2)[CH2:3][CH2:4]1
Reactant: COc1ccc2nccc([C@@H](O)CN3CCC(N)CC3)c2n1
Reactant: O=Cc1ccc2c(n1)NCCC2
Agent: O=S(=O)([O-])[O-]
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CCO
Product: COc1ccc2nccc([C@@H](O)CN3CCC(NCc4ccc5c(n4)NCCC5)CC3)c2n1
Reaction time: 36 h
Yield: 83 %

Procedure:
To a stirred solution of (R)-2-(4-aminopiperidin-1-yl)-1-(6-methoxy-[1,5]naphthyridin-4-yl)ethanol (2f) (0.30 g, 1.0 mmole) in CH2Cl2 (25 mL) and dry ethanol (10 mL) at RT was added 5,6,7,8-tetrahydro-[1,8]naphthyridine-2-carboxaldehyde (prepared according to the procedure of WO 98/08840, 0.17 g, 1.0 mmole) and granular Na2SO4 (approximately 200 mg). After 36 h, the reaction was filtered through a sintered-glass funnel and the filtrate was concentrated. The remaining residue was dissolved in dry ethanol and reacted with NaBH4 (0.04 g, 1.0 mmole). After 12 h at RT, the reaction was concentrated under vacuum and the residue was dissolved in a mixture of H2O (2 mL) and saturated aqueous NaHCO3 (10 mL). The aqueous solution was extracted with EtOAc (2×50 mL) and the combined organic phases were washed with brine then were dried over Na2SO4. Flash chromatography on silica gel (9:1 CHCl3/MeOH containing 5% NH4OH) afforded the title compound (0.37 g, 83%) as a white solid:
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[CH2:11][C:10]2[N:9]=[C:8]([C:12]([OH:14])=O)[CH:7]=[CH:6][C:5]=2[CH2:4][CH2:3]1.[NH2:16][C:17]([CH3:21])([CH3:20])[CH2:18][OH:19]>>[OH:19][CH2:18][C:17]([NH:16][C:12]([C:8]1[CH:7]=[CH:6][C:5]2[CH2:4][CH2:3][C:2]([CH3:1])([CH3:15])[CH2:11][C:10]=2[N:9]=1)=[O:14])([CH3:21])[CH3:20]
Reactant: CC(C)(N)CO
Reactant: CC1(C)CCc2ccc(C(=O)O)nc2C1
Product: CC1(C)CCc2ccc(C(=O)NC(C)(C)CO)nc2C1

Procedure:
The title compound was synthesized in analogy to Example 1, using 7,7-dimethyl-5,6,7,8-tetrahydro-quinoline-2-carboxylic acid (Example 143 d) and 2-amino-2-methyl-1-propanol (CAN 124-68-5) as starting materials, LC-MS (UV peak area/EIC) 99.7%, 277.1910(M+H)+.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)=[C:14]([CH2:38][OH:39])[C:15]([CH2:19][O:20][Si:21]([C:34]([CH3:37])([CH3:36])[CH3:35])([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=C[NH+]=CC=1.[O-][Cr](Cl)(=O)=O>C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([C:40]3[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=3)=[C:14]([CH:38]=[O:39])[C:15]([CH2:19][O:20][Si:21]([C:34]([CH3:37])([CH3:36])[CH3:35])([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)[Si](OCc1cc2cc(OCc3ccccc3)ccc2c(-c2ccccc2)c1CO)(c1ccccc1)c1ccccc1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CC(C)(C)[Si](OCc1cc2cc(OCc3ccccc3)ccc2c(-c2ccccc2)c1C=O)(c1ccccc1)c1ccccc1
Reaction time: 0.67 h

Procedure:
To a solution of alcohol (1.2 g) from Step 2 in CH2Cl2 (25 mL) was added molecular sieves powder (1 g, flame dried) and PCC (1 g). After 40 min, the reaction mixture was poured on a plug of SiO2 (wet with Et2O), and eluted with Et2O. The solvent was evaporated to give the title product.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([O:10][CH3:11])[CH:5]=1)=O.C(=O)([O-])[O-].[K+].[K+].Cl.[NH2:19][OH:20]>C(O)(C)C>[CH3:11][O:10][C:6]1[CH:5]=[C:4]([C:2](=[N:19][OH:20])[CH3:1])[CH:9]=[CH:8][CH:7]=1
Reactant: COc1cccc(C(C)=O)c1
Reactant: NO
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)O
Product: COc1cccc(C(C)=NO)c1
Temperature: 60 °C
Yield: 105.5 %

Procedure:
To a solution of 50 g of 3-methoxy acetophenone in 250 ml of isopropyl alcohol charged 92 g of potassium carbonate and 46 g of hydroxylamine hydrochloride followed by heating the contents to about 60° C. and maintained for about 2 hours. The reaction mass is cooled to about 28° C., filtered the separated solid and washed with 100 ml of isopropyl alcohol. The resulting filterate was distilled under vacuum at about 55° C. to yield 58 g of 1-(3-methoxy-phenyl)-ethanone oxime.
Reaction SMILES: [N:1]([CH2:4][CH2:5][S:6][CH3:7])=[C:2]=[O:3].[N+:8](=[C:10]1[N:14]=[CH:13][N:12]=[C:11]1[C:15]([NH2:17])=[O:16])=[N-:9]>CS(C)=O>[CH3:7][S:6][CH2:5][CH2:4][N:1]1[C:2](=[O:3])[N:14]2[CH:13]=[N:12][C:11]([C:15]([NH2:17])=[O:16])=[C:10]2[N:8]=[N:9]1
Reactant: CSCCN=C=O
Reactant: [N-]=[N+]=C1N=CN=C1C(N)=O
Solvent: CS(C)=O
Product: CSCCn1nnc2c(C(N)=O)ncn2c1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1-Isocyanato-2-methylsulfanyl-ethane (1.09 g, 9.31 mmol) was added drop wise to a suspension of 5-diazoimidazole-4-carboxamide (0.5 g, 3.65 mmol) in dry dimethylsulfoxide (5 mL) at room temperature under nitrogen. The resulting mixture was stirred at room temperature overnight. The reaction was quenched by the addition of ice and the solid product (brown) was removed by filtration, washed with Et2O, and purified using flash chromatography (SiO2) using MeCN:CH2Cl2 (0-100% MeCN) Yield: 52 mg, 26%. 1H NMR (400 MHz, d6-DMSO) δ ppm: 8.87 (1H, s), 7.80 (1H, s), 7.66 (1H, s), 4.48 (2H, t), 2.94 (2H, t).
Reaction SMILES: [C:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([CH2:14][C:15]([OH:17])=O)[CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[Li][CH3:19]>CCOCC>[C:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([CH2:14][C:15](=[O:17])[CH3:19])[CH2:9]1)([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]
Reactant: [Li]C
Reactant: CC(C)(C)OC(=O)N1CCCC(CC(=O)O)C1
Solvent: CCOCC
Product: CC(=O)CC1CCCN(C(=O)OC(C)(C)C)C1
Reaction time: 8 h

Procedure:
A solution of 2-2 (13.4 g, 55 mmol) in ether (500 mL) at 0° C. was treated dropwise with MeLi (87 mL, 121 mmol; 1.4 M/ether). After addition was complete, the cooling bath was removed and the reaction mixture was stirred overnight. The reaction mixture was then poured into an ice/water mixture and then extracted with ether. The ether extracts were washed with brine, dried (MgSO4), and concentrated. Flash chromatography (silica, 30% EtOAc/hexanes) gave 2-3 as a colorless oil.
Reaction SMILES: [CH2:1]([C:13]([O:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]([O:24][C:25]2[CH:30]=[CH:29][C:28]([O:31]CC3C=CC=CC=3)=[CH:27][CH:26]=2)=[O:23])=[CH:18][CH:17]=1)=[O:14])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]>[Pd].C(OCC)(=O)C>[CH2:1]([C:13]([O:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]([O:24][C:25]2[CH:26]=[CH:27][C:28]([OH:31])=[CH:29][CH:30]=2)=[O:23])=[CH:20][CH:21]=1)=[O:14])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCCC(=O)Oc1ccc(C(=O)Oc2ccc(OCc3ccccc3)cc2)cc1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCCCCCCCCCCCC(=O)Oc1ccc(C(=O)Oc2ccc(O)cc2)cc1
Reaction time: 6 h
Yield: 91.8 %

Procedure:
{circle around (4)}: A mixture comprising 3.3 g of 4-(4′-n-dodecylcarbonyloxyphenylcarbonyloxy)-1-benzyloxybenzene, 0.3 g of palladium/carbon and 20 g of ethyl acetate was stirred for 6 hours under hydrogen atmosphere. Then, palladium/carbon was filtered off, followed by distilling off ethyl acetate from the filtrate. The resultant residue was recrystallized from toluene, whereby 2.5 g of 4-(4′-n-dodecylcarbonyloxyphenylcarbonyloxy)phenol was obtained in the form of a colorless crystal.
Reaction SMILES: [CH3:1][CH:2]1[CH2:7][CH:6]([CH3:8])[CH2:5][NH:4][CH2:3]1.Cl[C:10]1[N:15]=[C:14]([CH3:16])[C:13]([CH:17]([CH2:22][CH2:23][CH3:24])[C:18]([O:20][CH3:21])=[O:19])=[C:12]([C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=2)[N:11]=1>O1CCCC1>[CH3:1][CH:2]1[CH2:7][CH:6]([CH3:8])[CH2:5][N:4]([C:10]2[N:15]=[C:14]([CH3:16])[C:13]([CH:17]([CH2:22][CH2:23][CH3:24])[C:18]([O:20][CH3:21])=[O:19])=[C:12]([C:25]3[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=3)[N:11]=2)[CH2:3]1
Reactant: CC1CNCC(C)C1
Reactant: CCCC(C(=O)OC)c1c(C)nc(Cl)nc1-c1ccc(C)cc1
Solvent: C1CCOC1
Product: CCCC(C(=O)OC)c1c(C)nc(N2CC(C)CC(C)C2)nc1-c1ccc(C)cc1
Yield: 92.5 %

Procedure:
Methyl 2-(2-(3,5-dimethylpiperidin-1-yl)-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate was prepared according to the general method A starting from 3,5-Dimethylpiperidine (0.183 mL; 1.32 mmol) and methyl 2-(2-chloro-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate (0.110 g; 0.264 mmol) in tetrahydrofuran (2 mL). Purification by flash-chromatography on silica gel using a gradient of ethyl acetate (5-15%) in heptane furnished 100 mg (92%) of the title compound as an oil. ESI/APCI(+): 410 (M+H), 432 (M+Na). ESI/APCI(−): 408 (M−H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:17])[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([Cl:15])=[CH:10][C:9]=1[NH2:16])([CH3:4])([CH3:3])[CH3:2].C([O:22][C:23](=O)[CH2:24][C:25]([C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C:33]2[CH:34]=[N:35][C:36]([CH2:39][CH3:40])=[CH:37][CH:38]=2)[CH:28]=1)=[O:26])(C)(C)C>>[C:1]([O:5][C:6](=[O:17])[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([Cl:15])=[CH:10][C:9]=1[NH:16][C:23](=[O:22])[CH2:24][C:25]([C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C:33]2[CH:34]=[N:35][C:36]([CH2:39][CH3:40])=[CH:37][CH:38]=2)[CH:28]=1)=[O:26])([CH3:4])([CH3:2])[CH3:3]
Reactant: Cc1cc(NC(=O)OC(C)(C)C)c(N)cc1Cl
Reactant: CCc1ccc(-c2cccc(C(=O)CC(=O)OC(C)(C)C)c2)cn1
Product: CCc1ccc(-c2cccc(C(=O)CC(=O)Nc3cc(Cl)c(C)cc3NC(=O)OC(C)(C)C)c2)cn1

Procedure:
The title compound was prepared from (2-amino-4-chloro-5-methyl-phenyl)-carbamic acid tert-butyl ester (Example J22) (193 mg, 0.75 mmol) and 3-[3-(6-ethyl-pyridin-3-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (Example K23) (244 mg, 0.75 mmol) according to the general procedure M. Obtained as a light yellow foam (307 mg, 81%).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]([OH:12])=O)=[CH:4][N:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:25][CH:26]1[CH:31]2[CH2:32][CH2:33][N:28]([CH2:29][CH2:30]2)[CH2:27]1>>[NH2:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[C:5]([C:10]([NH:25][CH:26]2[CH:31]3[CH2:32][CH2:33][N:28]([CH2:29][CH2:30]3)[CH2:27]2)=[O:12])=[CH:4][N:3]=1
Reactant: COc1nc(N)ncc1C(=O)O
Reactant: NC1CN2CCC1CC2
Agent: O=C(n1ccnc1)n1ccnc1
Product: COc1nc(N)ncc1C(=O)NC1CN2CCC1CC2

Procedure:
Following the procedure of Example 22, 2-amino-4-methoxy-5-pyrimidinecarboxylic acid, 1,1'-carbonyldiimidazole and 3-aminoquinuclidine are reacted to give the title compound.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH3:12][S:13]([NH:16][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[N:23]=[C:22]([CH3:27])[CH:21]=[CH:20]2)(=[O:15])=[O:14]>C(Cl)Cl.C(=O)(O)[O-].[Na+]>[CH3:12][S:13]([NH:16][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][CH:26]=1)[N+:23]([O-:9])=[C:22]([CH3:27])[CH:21]=[CH:20]2)(=[O:14])=[O:15]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Cc1ccc2cc(NS(C)(=O)=O)ccc2n1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: Cc1ccc2cc(NS(C)(=O)=O)ccc2[n+]1[O-]
Reaction time: 17 h

Procedure:
m-Chloroperbenzoic acid ("MCPBA") (5.2 g) was added portionwise to a solution of 6-methanesulphonamido-2-methylquinoline (6 g) in methylene chloride and stirring was continued for 17 hours. The reaction mixture was then diluted with aqueous sodium bicarbonate and the organic layer was separated. The aqueous layer was extracted with methylene chloride. The combined organic layers were washed with aqueous sodium bicarbonate, dried (MgSO4) and evaporated in vacuo to give a solid which was recrystallised from ethanol to give the title compound, yield 1.6 g, m.p. 241°-243°.
Reaction SMILES: [CH3:1][N:2]([CH3:20])[CH:3]([C:9]1([C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)[CH2:12][CH2:11][CH2:10]1)[C:4](=[O:8])[CH2:5][CH2:6][CH3:7].O.Cl>O1CCCC1>[CH3:20][N:2]([CH3:1])[CH:3]([C:9]1([C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)[CH2:12][CH2:11][CH2:10]1)[CH:4]([OH:8])[CH2:5][CH2:6][CH3:7]
Reactant: CCCC(=O)C(N(C)C)C1(c2ccc(C)cc2)CCC1
Agent: Cl
Solvent: C1CCOC1
Solvent: O
Product: CCCC(O)C(N(C)C)C1(c2ccc(C)cc2)CCC1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
Boranedimethylsulphide complex (3 ml) was added dropwise under nitrogen over a period of 20 minutes to a solution of 1-dimethylamino-1-[1-(4-tolyl)cyclobutyl]pentan-2-one (1.85 g prepared as described in Example 16) in tetrahydrofuran (20 ml) and the resulting mixture stirred for 3 days at ambient temperature. The mixture was cooled to 0° C. and water (25 ml) and then 5N hydrochloric acid (25 ml) added. The mixture was basified and the tetrahydrofuran removed by evaporation. The residue was extracted with ether and the extracts washed with water, dried, filtered and evaporated to give an oil which was dissolved in petroleum ether (b.p. 80°-100° C.) and purified on a column packed with magnesia-silica gel sold under the trade name Florisil using petroleum ether (b.p. 80° to 100° C.) as eluant. The eluate was evaporated to give an oil which was distilled (215° C./1.5 mm Hg) to give 1-dimethylamino-1-[1 -(4-tolyl)cyclobutyl]pentan-2-ol.
Reaction SMILES: [BH4-].[Na+].[CH2:3](COC)[O:4]C.[F:9][C:10]1[C:18]([F:19])=[C:17](C(O)=O)[C:16]([F:23])=[C:15]([F:24])[C:11]=1[C:12]([OH:14])=O.Cl>O.C1(C)C=CC=CC=1>[F:24][C:15]1([CH2:3][OH:4])[C:16]([F:23])=[CH:17][C:18]([F:19])=[C:10]([F:9])[CH:11]1[CH2:12][OH:14]
Reactant: O=C(O)c1c(F)c(F)c(C(=O)O)c(F)c1F
Reactant: COCCOC
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: OCC1C(F)=C(F)C=C(F)C1(F)CO
Temperature: 50 °C
Reaction time: 1 h
Yield: 95 %

Procedure:
Into a 200 mL flask equipped with a reflux condenser, 2.58 g of sodium borohydride and 25 g of dimethoxyethane were charged. The obtained mixture was adjusted to 50° C. and then, a solution obtained by mixing 6.10 g of 2,3,5,6-tetrafluoroterephthalic acid with 20 g of dimethoxyethane was added dropwise thereto over 1 hour while stirring. The obtained mixture was stirred for 7 hours at 60° C. To the obtained reaction mixture, 20 g of toluene was added followed by cooling to 50° C. Eight point five grams of 35% by weight hydrochloric acid was added dropwise thereto over 1 hour to stir at 60° C. for 6 hours. To the obtained mixture, 30 g of water was added followed by separating to an organic layer and an aqueous layer. The aqueous layer was extracted twice with 30 g of ethyl acetate. The obtained organic layers were mixed and washed with 10 g of a saturated aqueous potassium carbonate solution and then with 10 g of water. The organic layer was concentrated and the obtained solids were recrystallized with toluene and hexane to obtain white powder crystals of 2,3,5,6-tetrafluorobenzenedimethanol. The crystals were analyzed by liquid chromatography absolute calibration curve method to find out that the purity thereof was 95.1%. Yield: 95%.
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][C:10]([C:13]([O:15][CH3:16])=[O:14])=[CH:9][C:8]=1[NH:17][C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])(=O)=O.[CH2:30]([Sn](CCCC)(CCCC)C#CC)[CH2:31][CH2:32]C>>[CH2:21]([O:20][C:18]([NH:17][C:8]1[CH:9]=[C:10]([CH:11]=[CH:12][C:7]=1[C:30]#[C:31][CH3:32])[C:13]([O:15][CH3:16])=[O:14])=[O:19])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: CC#C[Sn](CCCC)(CCCC)CCCC
Reactant: COC(=O)c1ccc(OS(=O)(=O)C(F)(F)F)c(NC(=O)OCc2ccccc2)c1
Product: CC#Cc1ccc(C(=O)OC)cc1NC(=O)OCc1ccccc1
Yield: 85.5 %

Procedure:
Methyl 3-benzyloxycarbonylamino-4-(1-propynyl)benzoate (1.34 g) was prepared from 2-benzyloxycarbonylamino-4-methoxycarbonylphenyl trifluoromethanesulfonate (2.1 g) and tributyl(1-propynyl)stannane (2.49 g) in a similar manner to that of Preparation 1 (2).
Reaction SMILES: [CH3:1][O:2][C:3]([NH:5][CH:6]=[CH:7][C:8]1[CH:18]=[CH:17][C:11]([O:12][CH2:13][CH:14]2[O:16][CH2:15]2)=[CH:10][CH:9]=1)=[O:4].[NH2:19][CH:20]([CH3:25])[CH2:21][C:22]([NH2:24])=[O:23]>C(#N)C>[CH3:1][O:2][C:3]([NH:5][CH:6]=[CH:7][C:8]1[CH:18]=[CH:17][C:11]([O:12][CH2:13][CH:14]([OH:16])[CH2:15][NH:19][CH:20]([CH3:25])[CH2:21][C:22](=[O:23])[NH2:24])=[CH:10][CH:9]=1)=[O:4]
Reactant: COC(=O)NC=Cc1ccc(OCC2CO2)cc1
Reactant: CC(N)CC(N)=O
Solvent: CC#N
Product: COC(=O)NC=Cc1ccc(OCC(O)CNC(C)CC(N)=O)cc1
Reaction time: 20 h

Procedure:
7.5 g (0.03 mol) of 1-[p-(2-methoxycarbonylaminovinyl)-phenoxy]-2,3-epoxypropane are dissolved in 75 ml of acetonitrile and added dropwise to a boiling stirred solution of 3.34 g (0.029 mol) of β-aminobutyric acid amide in 75 ml of aceto-nitrile. The mixture is stirred for 20 hours under reflux, the solvent is removed by distillation under reduced pressure and the oil which remains is partitioned between 350 ml of 0.1 N hydrochloric acid and 300 ml of ethyl acetate. The hydrochloric acid extract is separated off, rendered alkaline with sodium carbonate and extracted four times with 100 ml of ethyl acetate at a time. The organic phases are dried over sodium sulphate and evaporated under reduced pressure. The resulting oil yields 1-[p-(2-methoxycarbonylaminovinyl)-phenoxy]-2-hydroxy-3-(2-carbamoyl-1-methyl-ethylamino)-propane, of melting point 109°-111°C, from acetone acetate.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][S:5][C:6]1[CH:12]=[CH:11][C:9]([OH:10])=[CH:8][C:7]=1[OH:13].[NH:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1>>[O:17]1[CH2:18][CH2:19][N:14]([CH2:2][CH2:3][CH2:4][S:5][C:6]2[CH:12]=[CH:11][C:9]([OH:10])=[CH:8][C:7]=2[OH:13])[CH2:15][CH2:16]1
Reactant: Oc1ccc(SCCCCl)c(O)c1
Reactant: C1COCCN1
Product: Oc1ccc(SCCCN2CCOCC2)c(O)c1

Procedure:
4 g of 4-(3-chloropropylthio)resorcin and 8 ml of morpholine are heated for two hours at 100° C. The mixture is poured into ice-cold water and extracted with ethyl acetate. The organic phases are washed, dried and concentrated under vacuum. The yellow oil is crystallized from ethyl acetate to lead to white crystals having a melting point of: 99° C.
Reaction SMILES: C[O:2][C:3](=[O:17])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:5]=1[CH:14]1[CH2:16][CH2:15]1.[OH-].[Na+]>C(O)C>[CH:14]1([C:5]2[CH:6]=[C:7]([C:10]([F:11])([F:12])[F:13])[CH:8]=[CH:9][C:4]=2[C:3]([OH:17])=[O:2])[CH2:16][CH2:15]1
Reactant: COC(=O)c1ccc(C(F)(F)F)cc1C1CC1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)c1ccc(C(F)(F)F)cc1C1CC1
Temperature: 80 °C
Yield: 43.1 %

Procedure:
To a suspension of 485 mg (1.986 mmol) 2-cyclopropyl-4-trifluoromethyl-benzoic acid methyl ester in 8 ml ethanol at room temperature, was added 1.99 ml (3.972 mmol) 2N NaOH. The mixture was heated in a 80° C. oil bath for 30 minutes. The solution was cooled to room temperature and the ethanol was evaporated. The residue was diluted with water, acidified with 2N HCl to pH 2 and dichloromethane was added. The aqueous phase was extracted twice with dichloromethane. The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified on silica gel (eluent: heptane/ethyl acetate 0 to 100%) to provide 0.197 g (27%) of the title compound as a light yellow solid. MS (m/e): 229.0 (M−H).