Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: N[C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[S:21]([C:24]([F:27])([F:26])[F:25])(=[O:23])=[O:22].C(#N)C.N(OC(C)(C)C)=O.C(Br)(Br)[Br:39]>>[Br:39][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[S:21]([C:24]([F:27])([F:26])[F:25])(=[O:23])=[O:22]
Reactant: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1S(=O)(=O)C(F)(F)F
Reactant: BrC(Br)Br
Agent: CC(C)(C)ON=O
Solvent: CC#N
Product: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(Br)c1S(=O)(=O)C(F)(F)F
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A suspension of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethanesulphonylpyrazole (43.8 g) was stirred in a mixture of bromoform (141 ml) and dry acetonitrile (63 ml ). Tert-butyl nitrite (29.9 g) was added dropwise during 5 minutes, and the mixture heated at 60°-70° C. for 2.75 hours. After cooling to 25° C. a further addition of tert-butyl nitrite (29.9 g) was made, and the heating resumed for 2 hours. Evaporation in vacuo gave a yellow oily solid which was triturated with hexane and filtered off. Two recrystallisations from toluene/hexane gave 5-bromo-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl) 4-trifluoromethanesulphonylpyrazole as a yellow solid (34.0 g), m.p. 136°-137° C.
Reaction SMILES: Br[CH2:2][C:3](=O)[C:4]([O:6][CH2:7][CH3:8])=[O:5].COCCOC.[NH2:16][C:17]1[CH:22]=[N:21][CH:20]=[CH:19][N:18]=1>CCO>[CH2:7]([O:6][C:4]([C:3]1[N:16]=[C:17]2[CH:22]=[N:21][CH:20]=[CH:19][N:18]2[CH:2]=1)=[O:5])[CH3:8]
Reactant: Nc1cnccn1
Reactant: CCOC(=O)C(=O)CBr
Solvent: CCO
Solvent: COCCOC
Product: CCOC(=O)c1cn2ccncc2n1
Temperature: 0 °C
Reaction time: 2.5 h

Procedure:
Ethyl bromopyruvate (62.9 g) was added to the DME (258 mL) solution of 2-aminopyrazine (24.8 g) at room temperature and stirred for 2.5 h. The reaction mixture was cooled to 0° C. and stirred for 30 min to afford a pale brown precipitate. The precipitate was filtered and washed with Et2O to give pale brown crystals. The suspension of the precipitate (66.1 g) in EtOH (1.29 L) was heated at reflux temperature to turn to clear solution. After refluxing for 2 h, the reaction mixture was concentrated under reduced pressure, then mixed with CHCl3 and saturated NaHCO3aq. The mixture was filtered through a pad of Celite and the separated organic layer was dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure. The residue was applied to silica gel column chromatography, then the column was eluted with CHCl3-MeOH (99/1˜97/3), and collected fractions were concentrated under reduced pressure followed by recrystallization from CHCl3-Et2O. The titled compound was obtained as pale pink crystals. Yield: 10.9 g, 22%).
Reaction SMILES: C([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[C:13](OCC)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:5]1=[O:23])(=O)C.[CH2:24]([N:26]([CH2:29][C:30]([N:32]([C:34]1[CH:40]=[CH:39][C:37]([NH2:38])=[CH:36][CH:35]=1)[CH3:33])=[O:31])[CH2:27][CH3:28])[CH3:25].[OH-].[Na+]>CN(C=O)C.CO>[CH2:24]([N:26]([CH2:29][C:30]([N:32]([C:34]1[CH:40]=[CH:39][C:37]([NH:38]/[C:13](=[C:6]2\[C:5](=[O:23])[NH:4][C:12]3[C:7]\2=[CH:8][CH:9]=[CH:10][CH:11]=3)/[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)=[CH:36][CH:35]=1)[CH3:33])=[O:31])[CH2:27][CH3:28])[CH3:25]
Reactant: CCN(CC)CC(=O)N(C)c1ccc(N)cc1
Reactant: CCOC(=C1C(=O)N(C(C)=O)c2ccccc21)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: CO
Product: CCN(CC)CC(=O)N(C)c1ccc(N/C(=C2\C(=O)Nc3ccccc32)c2ccccc2)cc1

Procedure:
Prepared analogously to Example 43 from 1-acetyl-3-(1-ethoxy-1-phenyl-methylidene)-2-indolinone and 4-(N-diethylaminomethylcarbonyl-N-methyl-amino)-aniline in DMF and subsequent treatment with sodium hydroxide solution in methanol.
Reaction SMILES: [N:1]1([C:6]2[CH:23]=[CH:22][C:9]([O:10][CH2:11][CH2:12][C@@H:13]3[CH2:15][C@@H:14]3[CH:16]3[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]3)=[CH:8][CH:7]=2)[CH:5]=[N:4][N:3]=[N:2]1.CCN(C(C)C)C(C)C.[C:33]([N:37]=[C:38]=[O:39])([CH3:36])([CH3:35])[CH3:34]>CN(C=O)C>[C:33]([NH:37][C:38]([N:19]1[CH2:20][CH2:21][CH:16]([C@H:14]2[CH2:15][C@H:13]2[CH2:12][CH2:11][O:10][C:9]2[CH:8]=[CH:7][C:6]([N:1]3[CH:5]=[N:4][N:3]=[N:2]3)=[CH:23][CH:22]=2)[CH2:17][CH2:18]1)=[O:39])([CH3:36])([CH3:35])[CH3:34]
Reactant: CC(C)(C)N=C=O
Reactant: c1cc(-n2cnnn2)ccc1OCC[C@@H]1C[C@@H]1C1CCNCC1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)NC(=O)N1CCC([C@H]2C[C@H]2CCOc2ccc(-n3cnnn3)cc2)CC1
Reaction time: 0.33 h

Procedure:
To a solution of 4-((1R,2S)-2-(2-(4-(1H-tetrazol-1-yl)phenoxy)ethyl)cyclopropyl)piperidine (20 mg, 0.064 mmol) in DMF (0.7 ml) under nitrogen at RT was added DIPEA (0.022 ml, 0.128 mmol) followed by t-butyl isocyanate (drop). At 20 minutes, LC/MS showed no SM left. Quenched with formic acid (4.90 μl, 0. The fractions containing product were collected and dried via GenoVac to afford the title compound. GPR119 Human EC50: 14.7 nM
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:17][CH:18]([OH:35])[C:19](=[O:34])[NH:20][CH2:21][C:22]1[C:27]([O:28][CH3:29])=[CH:26][C:25]([O:30][CH3:31])=[CH:24][C:23]=1[O:32][CH3:33])[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.[C:43]1([CH3:53])[CH:48]=[CH:47][C:46]([S:49](Cl)(=[O:51])=[O:50])=[CH:45][CH:44]=1>C(Cl)Cl.CN(C)C1C=CN=CC=1>[C:13]([O:12][C:10](=[O:11])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:17][CH:18]([O:35][S:49]([C:46]1[CH:47]=[CH:48][C:43]([CH3:53])=[CH:44][CH:45]=1)(=[O:51])=[O:50])[C:19](=[O:34])[NH:20][CH2:21][C:22]1[C:27]([O:28][CH3:29])=[CH:26][C:25]([O:30][CH3:31])=[CH:24][C:23]=1[O:32][CH3:33])([CH3:14])([CH3:16])[CH3:15]
Reactant: COc1cc(OC)c(CNC(=O)C(O)C[C@H](NC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)c(OC)c1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1cc(OC)c(CNC(=O)C(C[C@H](NC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)OS(=O)(=O)c2ccc(C)cc2)c(OC)c1
Temperature: 0 °C
Reaction time: 8 h
Yield: 95.6 %

Procedure:
To a stirred solution of 10 (0.546 g, 1.09 mmol) in CH2Cl2 (10 mL) cooled with ice bath (0° C.) was added Et3N (0.76 mL, 5.45 mmol), p-toluenesulfonyl chloride (TsCl, 0.416 g, 2.18 mmol) and catalytic amount 4-dimethylaminopyridine (DMAP, 0.11 mmol, 0.013 g). After maintaining at 0° C. for 15 min., the ice bath was removed, the reaction kept at r.t. overnight and then submitted to standard workup with CH2Cl2. The crude product was purified by FC (EtOAc/Hexanes, 40/60 to 50/50, V/V) to provide a pale white solid 11 (0.68 g, 96%). HPLC of 11: isomer one: 50%, Rt=12.53 min; isomer two: 50%, Rt=18.72 min; [column: Lux 3u Cellulose-1 (150×4.6 mm), UV detector, 210 nm, 5% 2-propanol in hexanes; flow rate: 1.0 mL/min]. 1HNMR (200 MHz, CD2Cl2) δ 7.72 (d, 2H, J=8.2 Hz), 7.28 (d, 2H, J=8.2 Hz), 6.79 (d, 1H, J=20.6 Hz), 6.15 (s, 2H), 5.14 (br s, 1H), 4.83 (t, 1H, J=6.8 Hz), 4.50-3.94 (m, 3H), 3.82 (s, 6H), 3.81 (s, 3H), 2.41 (s, 3H), 2.28-2.11 (m, 2H), 1.43 (s, 9H), 1.42 (s, 9H). 13C NMR (50 MHz, CD2Cl2) δ 171.0, 167.3, 161.8, 159.9, 155.8, 146.3, 133.3, 130.6, 128.5, 128.4, 106.6, 106.4, 91.3, 82.8, 82.5, 80.2, 78.0, 77.7, 56.4, 56.0, 35.7, 35.3, 32.9, 28.7, 28.3, 22.0. HRMS calcd for C31H45N2O11S (M+H)4: 653.2744. found: 653.2734, 653.2739.
Reaction SMILES: [CH3:1][C:2]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:3]=1[CH:4]=O.C([O-])(=O)C.[NH4+].[N+:18]([CH3:21])([O-:20])=[O:19]>C(O)(=O)C>[CH3:1][C:2]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:3]=1/[CH:4]=[CH:21]/[N+:18]([O-:20])=[O:19]
Reactant: Cc1ccc([N+](=O)[O-])cc1C=O
Reactant: C[N+](=O)[O-]
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CC(=O)O
Product: Cc1ccc([N+](=O)[O-])cc1/C=C/[N+](=O)[O-]

Procedure:
Adapting literature known protocols (U.S. Pat. No. 8,344,028; and Kabalka and Varma, Org. Prep. Proced. Int., 1987, 19(4-5), 283-328), 1-methyl-4-nitro-2-[(E)-2-nitrovinyl]benzene (19a) is prepared by heating a solution of commercial 2-methyl-5-nitro-benzaldehyde (5j) (1.65 g, 10.0 mmol) (for a synthesis of (5j) see also Example 5, Method B), ammonium acetate (NH4OAc) (1.31 g, 17.0 mmol) in a mixture of nitromethane (MeNO2) (1.61 mL, 1.83 g, 30.0 mmol) and acetic acid (HOAc) (10.0 mL) to reflux for about 3 hours. Aqueous work-up and purification by silica gel column chromatography using ethyl acetate (EtOAc) and hexanes mixtures afford the title compound (19a).
Reaction SMILES: [CH2:1]([S:13]([C:16]1[CH:24]=[CH:23][CH:22]=[CH:21][C:17]=1[C:18](O)=[O:19])(=[O:15])=[O:14])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].CN(C)C=O.C(Cl)(=O)C([Cl:33])=O>C(Cl)Cl>[CH2:1]([S:13]([C:16]1[CH:24]=[CH:23][CH:22]=[CH:21][C:17]=1[C:18]([Cl:33])=[O:19])(=[O:15])=[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: O=C(Cl)C(=O)Cl
Reactant: CCCCCCCCCCCCS(=O)(=O)c1ccccc1C(=O)O
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CCCCCCCCCCCCS(=O)(=O)c1ccccc1C(=O)Cl
Temperature: 25 °C

Procedure:
The o-dodecanesulfonylbenzoic acid (30.0 g, 0.084 mol) was dissolved in 100 ml of methylene chloride, then 0.5 ml of N,N-dimethylformamide was added, and they were stirred at room temperature. Then 12 ml of oxalyl chloride was added dropwise over 15 min, and after the addition the reaction mixture was stirred for 1 hour. The reaction solution was concentrated, to obtain o-dodecanesulfonylbenzoyl chloride.
Reaction SMILES: [Si:1]([O:8][CH2:9][C@@H:10]([NH:14][C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]=[CH:17][C:16]=1[NH2:25])[CH:11]([CH3:13])[CH3:12])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl.[Cl:27][CH2:28][C:29](=N)OCC.C(Cl)(Cl)Cl.C(=O)(O)[O-].[Na+]>ClCCCl>[Si:1]([O:8][CH2:9][C@@H:10]([N:14]1[C:15]2[C:24]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[N:18]=[CH:17][C:16]=2[N:25]=[C:29]1[CH2:28][Cl:27])[CH:11]([CH3:13])[CH3:12])([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2]
Reactant: CC(C)[C@@H](CO[Si](C)(C)C(C)(C)C)Nc1c(N)cnc2ccccc12
Reactant: CCOC(=N)CCl
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: ClCCCl
Product: CC(C)[C@@H](CO[Si](C)(C)C(C)(C)C)n1c(CCl)nc2cnc3ccccc3c21
Temperature: 70 °C
Yield: 82.9 %

Procedure:
N4-[(1S)-1-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-methylpropyl]quinoline-3,4-diamine (5.05 g, 14.0 mmol) was dissolved in 140 mL of dry 1,2-dichloroethane and the solution was stirred under N2. Ethyl 2-chloroethanimidoate hydrochloride (3.33 g, 21.1 mmol) was then added and the reaction mixture was heated to 70° C. After stirring for 2 days, the reaction mixture was cooled and treated with 70 mL of CHCl3 and 100 mL of saturated sodium bicarbonate (NaHCO3) solution. The layers were separated and the organic portion was washed with H2O and brine. The organic portion was then dried over Na2SO4, filtered and concentrated under reduced pressure. Chromatography (SiO2, 33%-50% ethyl acetate/hexanes) gave 1-[(1S)-1-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-methylpropyl]-2-(chloromethyl)-1H-imidazo[4,5-c]quinoline (4.85 g) as a dull yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][C:7]2[C:8](=[O:14])[NH:9][C:10](=[S:13])[NH:11][CH:12]=2)=[CH:4][CH:3]=1.[CH3:17]I.[OH-].[Na+]>O.C(O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C:7]2[C:8](=[O:14])[NH:9][C:10]([S:13][CH3:17])=[N:11][CH:12]=2)=[CH:15][CH:16]=1
Reactant: CI
Reactant: O=c1[nH]c(=S)[nH]cc1Cc1ccc(Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CSc1ncc(Cc2ccc(Cl)cc2)c(=O)[nH]1
Yield: 91.2 %

Procedure:
A Solution of 5-(4-chlorobenzyl)-2-thiouracil (50.5 g), methyl iodine (28.4 g) and sodium hydroxide (8.2 g) in water (200 ml) and ethanol (400 ml) was stirred at 60° for 30 minutes then allowed to cool. The crystalline product was filtered and washed with water to give 5-(4-chlorobenzyl)-2-methylthio-4-pyrimidone (48.6 g), m.p. 193°-194° (methanol/ethanol).
Reaction SMILES: [CH:1]([C:3]1[NH:4][CH:5]=[CH:6][CH:7]=1)=[O:2].[H-].[Na+].Cl[CH2:11][CH2:12][CH2:13][OH:14]>CN(C=O)C>[OH:14][CH2:13][CH2:12][CH2:11][N:4]1[CH:5]=[CH:6][CH:7]=[C:3]1[CH:1]=[O:2]
Reactant: OCCCCl
Reactant: O=Cc1ccc[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=Cc1cccn1CCCO
Yield: 91.9 %

Procedure:
The starting material may be prepared as follows. A solution of 2-formylpyrrole (1.0 g.) and a 50% w/w dispersion of sodium hydride in oil (0.72 g.) in DMF (20 ml.) was treated with 3-chloropropanol (1.03 g.) and the mixture heated at 90° for 18 hours and then evaporated to dryness. The residue was partitioned between water and ether, and the ether phase was dried and evaporated to dryness to give 1-(3-hydroxypropyl)-2-formylpyrrole (1.48 g.) which was used without further purification.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.[CH:12]1([CH:18]=O)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1>C(O)C.O>[Br:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][CH:3]=1)[O:11][CH:18]([CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)[CH2:9][C:8]2=[O:10]
Reactant: CC(=O)c1cc(Br)ccc1O
Reactant: O=CC1CCCCC1
Solvent: CCO
Solvent: O
Product: O=C1CC(C2CCCCC2)Oc2ccc(Br)cc21
Yield: 84.4 %

Procedure:
A mixture of 1-(5-bromo-2-hydroxy-phenyl)-ethanone (50 g, 0.23 mol), cyclohexanecarbaldehyde (26 g, 0.23 mol) and borax (89 g, 0.23 mol) in ethanol (300 mL) and H2O (500 mL) was refluxed overnight. The reaction mixture was cooled, diluted with an equal volume of H2O and extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4, filtered, and evaporated to give the crude product, which was purified by column chromatography to give 6-bromo-2-cyclohexylchroman-4-one (60 g, 83%). 1H-NMR (CDCl3): 1.05-1.33 (m, 5H), 1.67-1.81 (m, 5H), 1.95 (d, 1H), 2.64 (m, 2H), 4.15 (m, 1H), 6.86 (d, 1H), 7.51 (m, 1H), 7.94 (s, 1H).
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:9]([CH2:10][CH2:11][CH:12]([OH:20])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[O:8][C@@H:7]([N:21]2[CH:28]=[C:27]([CH2:29][CH3:30])[C:25](=[O:26])[NH:24][C:22]2=[O:23])[CH2:6]1)(=[O:3])[CH3:2].[CH3:31][S:32](Cl)(=[O:34])=[O:33]>N1C=CC=CC=1>[C:1]([O:4][C@@H:5]1[C@@H:9]([CH2:10][CH2:11][CH:12]([O:20][S:32]([CH3:31])(=[O:34])=[O:33])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[O:8][C@@H:7]([N:21]2[CH:28]=[C:27]([CH2:29][CH3:30])[C:25](=[O:26])[NH:24][C:22]2=[O:23])[CH2:6]1)(=[O:3])[CH3:2]
Reactant: CS(=O)(=O)Cl
Reactant: CCc1cn([C@H]2C[C@H](OC(C)=O)[C@@H](CCC(O)Cc3ccccc3)O2)c(=O)[nH]c1=O
Solvent: c1ccncc1
Product: CCc1cn([C@H]2C[C@H](OC(C)=O)[C@@H](CCC(Cc3ccccc3)OS(C)(=O)=O)O2)c(=O)[nH]c1=O
Temperature: 0 °C
Reaction time: 8 h

Procedure:
A solution of 300 mg of 3'-O-acetyl-5'-[2(RS)-hydroxy-3-phenylpropyl]-2',5'-dideoxy-5-ethyluridine and 0.2 ml of methanesulphonyl chloride in 5 ml of pyridine was left to stand at 0° C. overnight. The mixture was poured on to 40 ml of ice/water, stirred and extracted with 40 ml of ethyl acetate. The extract was dried over anhydrous sodium sulphate and evaporated to yield 330 mg of 3'-O-acetyl-2',5'-dideoxy-5-ethyl-5'-[2(RS)-methanesulphonyloxy-3-phenylpropyl]uridine.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:16]=[CH:15][C:6]([CH2:7][S:8]([CH2:11][C:12](O)=O)(=[O:10])=[O:9])=[CH:5][C:4]=1[N+:17]([O-:19])=[O:18].[CH3:20][O:21][C:22]1[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[C:26]([O:32][CH3:33])[C:23]=1C=O.C(N)C1C=CC=CC=1>C(O)(=O)C>[CH3:1][O:2][C:3]1[CH:16]=[CH:15][C:6]([CH2:7][S:8](/[CH:11]=[CH:12]/[C:23]2[C:26]([O:32][CH3:33])=[CH:27][C:28]([O:30][CH3:31])=[CH:29][C:22]=2[O:21][CH3:20])(=[O:10])=[O:9])=[CH:5][C:4]=1[N+:17]([O-:19])=[O:18]
Reactant: COc1cc(OC)c(C=O)c(OC)c1
Reactant: COc1ccc(CS(=O)(=O)CC(=O)O)cc1[N+](=O)[O-]
Solvent: NCc1ccccc1
Solvent: CC(=O)O
Product: COc1cc(OC)c(/C=C/S(=O)(=O)Cc2ccc(OC)c([N+](=O)[O-])c2)c(OC)c1
Yield: 28 %

Procedure:
To a solution of 4-methoxy-3-nitrobenzyl sulfonylacetic acid (4.5 g, 15.5 mmol) in 30 mL of glacial acetic acid was added 2,4,6-trimethoxybenzaldehyde (3.05 g, 15.5 mmol) and a catalytic amount of benzylamine (0.6 mL). The resulting mixture was heated at reflux temperature for 6 h. The reaction mixture was then concentrated under reduced pressure to yield a gummy material. The gum was triturated with 2-propanol to yield a solid product. The solid product was recrystallized from a mixture of acetic acid and 2-propanol to provide the 2((E)-2-(4-methoxy-3-nitrobenzylsulfonyl)vinyl)-1,3,5-trimethoxybenzene product in 28% yield. m.p. 186-187° C.
Reaction SMILES: C(OC([NH:8][CH2:9][C:10](O)=[O:11])=O)(C)(C)C.P(C#N)(OCC)(OCC)=O.[NH2:23][CH:24]1[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=2[N:28]([C:35](=[O:52])[C:36]2[CH:41]=[CH:40][C:39]([NH:42][C:43](=[O:51])[C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=3[CH3:50])=[CH:38][CH:37]=2)[CH2:27][CH2:26][CH2:25]1.C(N(CC)CC)C>CN(C)C=O>[NH2:8][CH2:9][C:10]([NH:23][CH:24]1[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=2[N:28]([C:35](=[O:52])[C:36]2[CH:41]=[CH:40][C:39]([NH:42][C:43](=[O:51])[C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=3[CH3:50])=[CH:38][CH:37]=2)[CH2:27][CH2:26][CH2:25]1)=[O:11]
Reactant: Cc1ccccc1C(=O)Nc1ccc(C(=O)N2CCCC(N)c3ccccc32)cc1
Reactant: CC(C)(C)OC(=O)NCC(=O)O
Agent: CCOP(=O)(C#N)OCC
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cc1ccccc1C(=O)Nc1ccc(C(=O)N2CCCC(NC(=O)CN)c3ccccc32)cc1
Reaction time: 0.5 h
Yield: 8 %

Procedure:
To a solution of t-butoxycarbonylglycine (0.84 g) in dimethylformamide (20 ml) are added diethyl cyanophosphate (0.73 ml) and 5-amino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (1.74 g), and further thereto is added triethylamine (1.8 ml) under ice-cooling. The mixture is stirred for 30 minutes, and then stirred at room temperature overnight. The reaction solution is concentrated and water is added to the resulting residue. The precipitated crystal is collected by filtration, washed with water, and recrystallized from ethyl acetate to give 5-(2-aminoacetylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (E) (0.16 g). Separately, the filtrate is concentrated and purified by silica gel column chromatography (eluent; dichloromethane:methanol=50:1), and recrystallized from diethyl ether to give 5-[2-(t-butoxycarbonylamino)acetylamino]-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (F) (0.19 g).
Reaction SMILES: Br[CH2:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][N:7]=[C:6]2[NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[CH:15]=1.[Na].[SH:22][C:23]1[NH:24][C:25]2[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=2[N:27]=1>>[N:24]1[C:25]2[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=2[NH:27][C:23]=1[S:22][CH2:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][N:7]=[C:6]2[NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[CH:15]=1
Reactant: Cc1cccc(Nc2ncnc3ccc(CBr)cc23)c1
Reactant: Sc1nc2ccccc2[nH]1
Agent: [Na]
Product: Cc1cccc(Nc2ncnc3ccc(CSc4nc5ccccc5[nH]4)cc23)c1
Yield: 59 %

Procedure:
Using an analogous procedure to that described in Example 34, 6-bromomethyl-4-(3-methylanilino)quinazoline was reacted with 2-mercaptobenzimidazole sodium salt to give 6-(2-benzimidazolylthiomethyl)-4-(3-methylanilino)quinazoline in 59% yield, m.p. 123°-129° C.;
Reaction SMILES: S(S([O-])(=O)=O)([O-])(=O)=O.[Na+].[Na+].[C:11]([C:15]1[CH:20]=[C:19]([N:21]=O)[CH:18]=[C:17]([C:23]([CH3:26])([CH3:25])[CH3:24])[C:16]=1[OH:27])([CH3:14])([CH3:13])[CH3:12].[OH-].[Na+].C1C=CC=CC=1>O>[C:11]([C:15]1[CH:20]=[C:19]([NH2:21])[CH:18]=[C:17]([C:23]([CH3:26])([CH3:25])[CH3:24])[C:16]=1[OH:27])([CH3:14])([CH3:13])[CH3:12]
Reactant: CC(C)(C)c1cc(N=O)cc(C(C)(C)C)c1O
Agent: O=S(=O)([O-])S(=O)(=O)[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: c1ccccc1
Solvent: O
Product: CC(C)(C)c1cc(N)cc(C(C)(C)C)c1O
Reaction time: 0.75 h

Procedure:
2,6-di tert.butyl-4-aminophenol was prepared by adding in a nitrogen atmosphere, a solution of 70 grams of sodium dithionate in 300 milliliters of water to a mixture of 23.5 grams of 2,6-di tert.butyl-4-nitrosophenol, 80 milliliters of 5 N sodium hydroxide solution and 160 milliliters of water. The addition was accomplished in 45 minutes at 24° C. to 41° C. After stirring for 21/4 hours, 100 milliliters of benzene was added to dissolve the solid product, and the layers were separated.
Reaction SMILES: C([O:3][C:4](=[O:34])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21](=[O:27])[NH:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[CH:17][C:16]=2[CH2:28][S:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH:7]=1)C.[OH-].[Li+]>CO.O>[C:23]([NH:22][C:21]([C:18]1[CH:19]=[CH:20][C:15]([O:14][C:8]2[CH:7]=[C:6]([CH2:5][C:4]([OH:34])=[O:3])[CH:11]=[CH:10][C:9]=2[O:12][CH3:13])=[C:16]([CH2:28][S:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH:17]=1)=[O:27])([CH3:25])([CH3:26])[CH3:24]
Reactant: CCOC(=O)Cc1ccc(OC)c(Oc2ccc(C(=O)NC(C)(C)C)cc2CSC(C)(C)C)c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: COc1ccc(CC(=O)O)cc1Oc1ccc(C(=O)NC(C)(C)C)cc1CSC(C)(C)C

Procedure:
[3-(4-tert-Butylcarbamoyl-2-tert-butylsulfanylmethyl-phenoxy)-4-methoxy-phenyl]-acetic acid ethyl ester (0.46 mmol) was treated with lithium hydroxide in MeOH and H2O at 60° C. for 20 minutes to give the title compound.
Reaction SMILES: [CH:1]1[C:11]2[C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[NH:8][C:7]3[CH:16]=[CH:17][CH:18]=[CH:19][C:6]=3[C:5]=2[CH:4]=[CH:3][CH:2]=1.[Br:20][C:21]1[CH:26]=[CH:25][C:24](Br)=[CH:23][CH:22]=1.[OH-].[K+].C1C2C(CCCC2)CCC1>[Cu].C(Cl)(Cl)Cl>[Br:20][C:21]1[CH:26]=[CH:25][C:24]([N:8]2[C:9]3[CH:15]=[CH:14][CH:13]=[CH:12][C:10]=3[C:11]3[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=3[C:6]3[CH:19]=[CH:18][CH:17]=[CH:16][C:7]2=3)=[CH:23][CH:22]=1
Reactant: c1ccc2c(c1)Nc1ccccc1-c1ccccc1-2
Reactant: Brc1ccc(Br)cc1
Agent: [Cu]
Agent: [K+]
Agent: [OH-]
Solvent: ClC(Cl)Cl
Solvent: C1CCC2CCCCC2C1
Product: Brc1ccc(N2c3ccccc3-c3ccccc3-c3ccccc32)cc1
Temperature: 200 °C
Yield: 25.1 %

Procedure:
A mixture of 9.2 g (38 mmol) of 9H-tribenz[b,d,f]azepine (synthesized in accordance with J. Org. Chem., vol. 56, p. 3906 (1991)), 44.8 g (190 mmol) of 1,4-dibromobenzene, 5.6 g (100 mmol) of potassium hydroxide, 1.6 g (25 mmol) of copper powder, and 50 ml of decalin was heated at an external temperature of 200° C. for 36 hours in a nitrogen stream while stirring. The reaction mixture was cooled nearly to room temperature, chloroform was added thereto, followed by filtration using Celite to remove the insoluble matter. The filtrate was concentrated. To remove decalin, n-hexane was added to the residue, followed by filtration. The filter cake was purified by silica gel column chromatography to give 3.8 g (25%) of 9-(4-bromophenyl)-9H-tribenz[b,d,f]azepine.
Reaction SMILES: C([O:8][CH2:9][CH:10]([CH3:24])[CH2:11][CH2:12][CH2:13][C:14]1([CH3:23])[O:22][CH:15]1[CH2:16][CH2:17][C:18](=[O:21])[CH2:19][Br:20])C1C=CC=CC=1.O(CC(C)CCCC(C)=CCCC(=O)CBr)[Si:26]([C:39]([CH3:42])([CH3:41])[CH3:40])([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>>[O:8]([CH2:9][CH:10]([CH3:24])[CH2:11][CH2:12][CH2:13][C:14]1([CH3:23])[O:22][CH:15]1[CH2:16][CH2:17][C:18](=[O:21])[CH2:19][Br:20])[Si:26]([C:39]([CH3:42])([CH3:41])[CH3:40])([C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: CC(CCCC1(C)OC1CCC(=O)CBr)COCc1ccccc1
Reactant: CC(=CCCC(=O)CBr)CCCC(C)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Product: CC(CCCC1(C)OC1CCC(=O)CBr)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C

Procedure:
Following the procedure for the preparaton of 11-benzyloxy-1-bromo-6,10-dimethyl-5,6-epoxy-undecan-2-one, but employing 11-t-butyldiphenylsiloxy-1-bromo-6,10 -dimethyl-2-oxo-undec-5-ene (1.6 g) in place of 11-benzyloxy-1-bromo-6,10-dimethyl-2-oxo-undec-5-one, 11-t-butyldiphenylsiloxy-1-bromo-6,10-dimethyl-5,6-epoxy-undecan-2-one (1.3 g) is obtained as a yellow oil: