Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:4][CH:3]=1.[C:17](OC(=O)C)(=[O:19])[CH3:18]>C1C=CC=CC=1>[C:17]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[CH:6][CH:7]=1)(=[O:19])[CH3:18]
Reactant: CC(=O)OC(C)=O
Reactant: Nc1ccc(-c2nc3ccccc3s2)cc1
Solvent: c1ccccc1
Product: CC(=O)Nc1ccc(-c2nc3ccccc3s2)cc1
Yield: 87.7 %

Procedure:
A solution of 2-(4'-aminophenyl)benzothiazole (0.5 g, 2.21 mmol) in benzene (30 ml) and acetic anhydride (0.5 g) was stirred at reflux for 4 hours and then cooled. The white precipitate was filtered off and washed with benzene. Recrystallisation from ethyl acetate gave a white powder (0.52 g, 88%), m.p. 227.2-229.1° C.
Reaction SMILES: [Cl:1][C:2]1[C:12]2[CH:11]=[CH:10][C:9]3[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=3[C:7](=[CH2:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1.C12BC(CCC1)CCC2.[O:27]1CCCC1>>[Cl:1][C:2]1[C:12]2[CH:11]=[CH:10][C:9]3[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=3[CH:7]([CH2:17][OH:27])[C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: C=C1c2ccccc2C=Cc2c(Cl)cccc21
Reactant: C1CCOC1
Agent: B1C2CCCC1CCC2
Product: OCC1c2ccccc2C=Cc2c(Cl)cccc21
Temperature: 0 °C
Reaction time: 0.75 h

Procedure:
To a solution of 1-chloro-5-methylene-dibenzo[a,d]cycloheptene (9.0 g) in dry tetrahydrofuran (60 ml), under an inert atmosphere was added 9-borabicyclo[3, 3,1]nonane (80.5 ml of a 0.5 molar solution in THF) at ambient temperature and the reaction mixture was then refluxed for 3h. After cooling, the reaction was quenched by the slow addition of 2N sodium hydroxide solution (180 ml) and 30% hydrogen peroxide (36 ml). After stirring vigorously at 0° C. for 45 minutes the reaction mixture was allowed to warm to room temperature over a 2h period then extracted into diethyl ether (3×250 ml). The combined organic layers were washed with brine (1×500 ml), dried (Na2SO4), filtered and concentrated in vacuo to leave a residue which was purified by chromatography on flash silica with 40% ethyl acetate in hexane as eluent to give the title compound (8.3 g) as a colourless oil. δ (360 MHz, CDCl3) 3.87 (2H, m, CH--CH2OH), 4.21 (1H, t, J=7.9 Hz, CH--CH2OH) 7.02 (1H, d, J=11.9 Hz, CHA =CHB) and 7.17-7.46 (8H, m, CHA =CHB and 7 aromatic protons). m/e 258 and 256 (M+).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[N:11]3[N:18]=[CH:19][C:20]([C:21]#[CH:22])=[C:10]3[N:9]=2)=[CH:4][CH:3]=1.Br[C:24]1[S:28][C:27]([S:29]([NH2:32])(=[O:31])=[O:30])=[CH:26][CH:25]=1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]([F:15])([F:17])[F:16])[N:11]3[N:18]=[CH:19][C:20]([C:21]#[C:22][C:24]4[S:28][C:27]([S:29]([NH2:32])(=[O:31])=[O:30])=[CH:26][CH:25]=4)=[C:10]3[N:9]=2)=[CH:4][CH:3]=1
Reactant: NS(=O)(=O)c1ccc(Br)s1
Reactant: C#Cc1cnn2c(C(F)(F)F)cc(-c3ccc(Cl)cc3)nc12
Product: NS(=O)(=O)c1ccc(C#Cc2cnn3c(C(F)(F)F)cc(-c4ccc(Cl)cc4)nc23)s1

Procedure:
The title compound was prepared from 5-(4-chloro-phenyl)-3-ethynyl-7-trifluoromethyl pyrazolo[1,5-a]pyrimidine (example C.4) (322 mg, 1.0 mmol) and 5-bromo-thiophene-2-sulfonic acid amide (242 mg, 1.0 mmol) according to general procedure II. Obtained as a yellow solid (247 mg, 51%). MS (ISP) 483.5 [(M+H)+]; mp 239-240° C.
Reaction SMILES: [OH:1][C:2]1[C:3]([CH2:8][CH2:9][C:10]2[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:11]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:20]([O:1][C:2]1[C:3]([CH2:8][CH2:9][C:10]2[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:11]=2)=[N:4][CH:5]=[CH:6][CH:7]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: COC(=O)c1ccc(CCc2ncccc2O)cc1
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(CCc2ncccc2OCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 62.9 %

Procedure:
A solution of methyl 4-[2-(3-hydroxy-2-pyridyl)ethyl]benzoate (1.1 g, 4.3 mmol) in DMF (30 ml) was treated with benzyl bromide (0.89 g, 5.2 mmol) and potassium carbonate (0.72 g, 5.2 mmol). The reaction was stirred at ambient temperature overnight and then, partitioned between EtOAc/water. The organic phase was washed well with water, dried (MgSO4) and evaporated. The residue was purified by chromatography (SiO2) eluting with CH2Cl2 /EtOAc to give methyl 4-[2-(3-benzyloxy-2-pyridyl)ethyl]benzoate (0.94 g, 53%) as a low melting yellow solid.
Reaction SMILES: C([O:3][C:4]([C:6]1[N:7]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:8]([S:11][CH3:12])=[N:9][CH:10]=1)=[O:5])C.[OH-].[K+:22]>>[K+:22].[CH3:12][S:11][C:8]1[N:7]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:18])([CH3:20])[CH3:19])[C:6]([C:4]([O-:5])=[O:3])=[CH:10][N:9]=1
Reactant: CCOC(=O)c1cnc(SC)n1COCC[Si](C)(C)C
Agent: [K+]
Agent: [OH-]
Product: CSc1ncc(C(=O)[O-])n1COCC[Si](C)(C)C
Temperature: 60 °C

Procedure:
To a solution of 2-methylsulfanyl-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazole-4-carboxylic acid ethyl ester (99 mg, 0.31 mmol)(as prepared in the previous step) was added 2 N KOH (0.16 mL, 0.32 mmol) and the mixture heated to 60° C. for 3 h. The mixture was concentrated and dried under vacuum to give the title compound as a white solid. Mass spectrum (ESI, m/z): Calcd. for C11H19KN2O3SSi, 289.1 (M-K+2H). found 288.7.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([C:10]([NH:17][CH2:18][CH2:19][C:20](OC)=[O:21])([CH2:14][CH2:15][CH3:16])[CH2:11][CH2:12][CH3:13])[CH2:8][CH3:9]>CCOCC>[OH:21][CH2:20][CH2:19][CH2:18][NH:17][C:10]([CH2:7][CH2:8][CH3:9])([CH2:14][CH2:15][CH3:16])[CH2:11][CH2:12][CH3:13]
Reactant: CCCC(CCC)(CCC)NCCC(=O)OC
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Product: CCCC(CCC)(CCC)NCCCO

Procedure:
Into a 500-ml three-necked flask fitted with a mechanical stirrer, a condenser and a dropping-funnel were introduced 3.8 g (0.17 mol) of lithium aluminium hydride and 130 ml of dry ether. To this mixture were slowly added 12.2 g (0.05 mol) of methyl 3-(1,1-di-n-propyl-n-butylamino)-propanoate, prepared as previously described. The reaction medium was heated under reflux for 12 hours and then hydrolyzed. The precipitate which formed was washed with ether, the ether was evaporated off and the oil so obtained was distilled.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:23]=[CH:24][CH:25]=1)[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:18][CH3:19])=[C:13]([O:16][CH3:17])[CH:14]=2)[C:9]([CH2:20][CH3:21])=[N:8][C:7]=1[OH:22].[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.C([O-])([O-])=O.[Na+].[Na+].O>CCO.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(COC)OC>[CH2:20]([C:9]1[C:10]2[C:15](=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=2)[C:6]([CH2:5][C:4]2[CH:3]=[C:2]([C:31]3[CH:32]=[CH:33][C:28]([O:27][CH3:26])=[CH:29][CH:30]=3)[CH:25]=[CH:24][CH:23]=2)=[C:7]([OH:22])[N:8]=1)[CH3:21]
Reactant: COc1ccc(B(O)O)cc1
Reactant: CCc1nc(O)c(Cc2cccc(Br)c2)c2cc(OC)c(OC)cc12
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Solvent: COCCOC
Product: CCc1nc(O)c(Cc2cccc(-c3ccc(OC)cc3)c2)c2cc(OC)c(OC)cc12
Temperature: 25 °C

Procedure:
To a stirred solution of 4-(3-bromobenzyl)-1-ethyl-6,7-dimethoxyisoquinolin-3-ol SLA 28138 (79 mg, 0.196 mmol) in EtOH (0.9 mL) in a 20 mL microwave vial equipped with a magnetic stirrer were added 4-methoxyphenylboronic acid (60 mg, 0.393 mmol), Pd(PPh3)2Cl2 (10.0 mg), a 2 N aq. Na2CO3 solution (0.3 mL), H2O (2.7 mL) and dimethoxyethane (3.5 mL) and the resulting mixture was stirred at 140° C. for 25 min. After cooling to RT, the mixture was diluted with EtOAc (30 mL) and the organic solution was passed through a celite plug, then washed with brine (10 mL). The celite plug was then further washed with CH2Cl2 (50 mL) and the organic layer was washed with brine (20 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 98:2) gave 1-ethyl-6,7-dimethoxy-4-((4′-methoxy-[1,1′-biphenyl]-3-yl)methyl)isoquinolin-3-ol. This free base was dissolved in CH2Cl2 (2 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.49 M HCl solution in MeOH (3 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 1-ethyl-6,7-dimethoxy-4-((4′-methoxy-[1,1-biphenyl]-3-yl)methyl)isoquinolin-3-ol hydrochloride 9 as a yellow solid (55 mg, 60% yield).
Reaction SMILES: [C:1]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:6]=[CH:5][C:4]([N:7]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:14][C:13]3[CH:12]=[C:11](Br)[CH:10]=[CH:9][C:8]2=3)=[CH:3][CH:2]=1.[C:28]1(B(O)O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl>C1(C)C=CC=CC=1.CO>[C:1]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:6]=[CH:5][C:4]([N:7]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:14][C:13]3[CH:12]=[C:11]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[CH:10]=[CH:9][C:8]2=3)=[CH:3][CH:2]=1
Reactant: OB(O)c1ccccc1
Reactant: Brc1ccc2c(c1)Cc1ccccc1N2c1ccc(-c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: c1ccc(-c2ccc(N3c4ccccc4Cc4cc(-c5ccccc5)ccc43)cc2)cc1
Temperature: 60 °C
Reaction time: 3 h
Yield: 78.4 %

Procedure:
10-(biphenyl-4-yl)-2-bromo-9,10-dihydroacridine compound (10 g, 24.3 mmol) was dissolved in toluene (300 mL) under a nitrogen atmosphere. Then, phenyl boronic acid (3.6 g, 29.2 mmol) was added thereto. To the resultant mixture solution, tetrakis triphenyl phosphine palladium (1.1 g, 0.97 mmol) and potassium carbonate (10.1 g, 72.9 mmol) were added. Then, distilled water (40 mL) was added thereto, followed by reflux-stirring for 3 hours. The resultant solution was cooled to about 60° C., and purified by silica gel. Then, a toluene layer was extracted. The extracted organic solvent was concentrated and removed, and methanol was added to produce a solid. Through filtration, a yellowish brown solid was obtained. It was dissolved by methylene chloride, and added with methanol in small amounts so as to obtain required 10-(biphenyl-4-yl)-2-phenyl-9,10-dihydroacridine compound (7.8 g, yield 78%, pale yellow solid).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([O:10][C:11](=[O:26])[NH:12][C:13]1[C:14]([CH3:25])=[N:15][O:16][C:17]=1[C:18]1[CH:23]=[CH:22][C:21](Br)=[CH:20][CH:19]=1)[CH3:9].[C:27]([OH:35])(=[O:34])[CH2:28][CH2:29][CH2:30][CH2:31][C:32]#[CH:33]>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([O:10][C:11]([NH:12][C:13]1[C:14]([CH3:25])=[N:15][O:16][C:17]=1[C:18]1[CH:23]=[CH:22][C:21]([C:33]#[C:32][CH2:31][CH2:30][CH2:29][CH2:28][C:27]([OH:35])=[O:34])=[CH:20][CH:19]=1)=[O:26])[CH3:9]
Reactant: Cc1noc(-c2ccc(Br)cc2)c1NC(=O)OC(C)c1ccccc1Cl
Reactant: C#CCCCCC(=O)O
Product: Cc1noc(-c2ccc(C#CCCCCC(=O)O)cc2)c1NC(=O)OC(C)c1ccccc1Cl

Procedure:
Prepared according to the procedure described in Example 2, Step 1, using the following starting materials: [5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-carbamic acid 1-(2-chloro-phenyl)-ethyl ester and 6-heptynoic acid. Mass spec. data (M+H)=481.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([O:14][C@H:15]([CH3:20])[C:16]([F:19])([F:18])[F:17])=[C:9]([CH:13]=1)[C:10]([OH:12])=O)(=[O:4])=[O:3].Cl.[CH3:22][C:23]1[N:24]=[C:25]([N:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[S:26][C:27]=1[C:28]([F:31])([F:30])[F:29]>>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([O:14][C@H:15]([CH3:20])[C:16]([F:19])([F:18])[F:17])=[C:9]([C:10]([N:35]2[CH2:36][CH2:37][N:32]([C:25]3[S:26][C:27]([C:28]([F:31])([F:29])[F:30])=[C:23]([CH3:22])[N:24]=3)[CH2:33][CH2:34]2)=[O:12])[CH:13]=1)(=[O:3])=[O:4]
Reactant: C[C@@H](Oc1ccc(S(C)(=O)=O)cc1C(=O)O)C(F)(F)F
Reactant: Cc1nc(N2CCNCC2)sc1C(F)(F)F
Agent: Cl
Product: Cc1nc(N2CCN(C(=O)c3cc(S(C)(=O)=O)ccc3O[C@H](C)C(F)(F)F)CC2)sc1C(F)(F)F
Yield: 57 %

Procedure:
Prepared in analogy to example 1 (b) from 5-methanesulfonyl-2-((R)-2,2,2-trifluoro-1-methyl-ethoxy)-benzoic acid (Example A16) and 1-(4-methyl-5-trifluoromethyl-thiazol-2-yl)-piperazine hydrochloride (Example 79(g)). The crude material was purified by chromatography (SiO2, ethyl acetate/heptane) to yield the title compound as a white crystalline solid (yield 57%). MS (m/e): 546.0 (M+H+, 100%).
Reaction SMILES: CC([O-])(C)C.[K+].[CH3:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[CH:10][CH:9]=1.[CH:22]1(Br)[CH2:26][CH2:25][CH2:24][CH2:23]1>CN(C=O)C>[CH:22]1([CH:14]([C:11]2[CH:10]=[CH:9][C:8]([CH3:7])=[CH:13][CH:12]=2)[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:26][CH2:25][CH2:24][CH2:23]1
Reactant: Cc1ccc(CC(=O)OC(C)(C)C)cc1
Reactant: BrC1CCCC1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1ccc(C(C(=O)OC(C)(C)C)C2CCCC2)cc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
33.5 g (0.3 mol) of potassium tert-butylate are initially introduced into 100 ml of anhydrous DMF at 0° C., and 51.6 g (0.25 mol) of tert-butyl 4-methylphenyl-acetate in 250 ml of anhydrous DMF are added dropwise. The mixture is stirred at 0° C. for 30 minutes, 32.2 ml (0.3 mol) of cyclopentyl bromide in 150 ml of anhydrous DMF are added dropwise at 5°-15° C. and the mixture is stirred at 25° C. for 20 hours. After concentration, the residue is partitioned between water and diethyl ether and the ether phase is dried over sodium sulphate and concentrated. The product crystallizes out.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([C:9]([NH:11][CH3:12])=[O:10])=[CH:4][N:3]=1.[NH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[NH:20][C:21](=[O:24])[CH:22]=[CH2:23].CCN(C(C)C)C(C)C.CO>CN1C(=O)CCC1.C(Cl)Cl.O>[C:21]([NH:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[NH:13][C:6]1[C:5]([C:9]([NH:11][CH3:12])=[O:10])=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=1)(=[O:24])[CH:22]=[CH2:23]
Reactant: C=CC(=O)Nc1ccccc1N
Reactant: CNC(=O)c1cnc(Cl)nc1Cl
Solvent: O
Solvent: CO
Solvent: CN1CCCC1=O
Product: C=CC(=O)Nc1ccccc1Nc1nc(Cl)ncc1C(=O)NC
Temperature: 120 °C

Procedure:
To a solution of 2,4-dichloro-N-methylpyrimidine-5-carboxamide (400 mg, 1.95 mmol) in NMP (1 ml), N-(2-aminophenyl)acrylamide (316 mg, 1.951 mmol) and DIPEA (503 mg, 3.902 mmol) were added and heated at 120° C. for 1 h. TLC showed completion of starting material (TLC system: 5% methanol in DCM (Rf): 0.3). The reaction mixture was diluted with water (30 ml) and extracted with ethyl acetate (3×15 ml). The organic layer was separated, dried over sodium sulphate, and concentrated. Crude compound was purified by column chromatography using silica gel (100-200 mesh) with 2% methanol in DCM to obtain 4-(2-acrylamidophenylamino)-2-chloro-N-methylpyrimidine-5-carboxamide as an off white solid. Yield: (180 mg, 28%). MS: m/z 332.1 (ES+, M+H).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[NH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25].CN(C=O)C.C(Cl)CCl>O>[C:1]([NH:4][C:5]1[CH:6]=[CH:7][C:8]([C:9]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[NH:21][C:22](=[O:28])[O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:11])=[CH:12][CH:13]=1)(=[O:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)Nc1ccccc1N
Reactant: CC(=O)Nc1ccc(C(=O)O)cc1
Solvent: CN(C)C=O
Solvent: O
Solvent: ClCCCl
Product: CC(=O)Nc1ccc(C(=O)Nc2ccccc2NC(=O)OC(C)(C)C)cc1
Yield: 77.6 %

Procedure:
To a 1 L round-bottom flask, were added 4-acetamidobenzoic acid (21.7 g, 122 mmol), tert-butyl (2-aminophenyl)carbamate (23.0 g, 111 mmol), and DMF (90 mL). The mixture was stirred to dissolve under N2, before EDC (27.6 g, 144 mmol) was added in one portion. The reaction mixture was stirred for 2 h, and water (270 mL) was added and stirred for 2 h. The precipitates were filtered, washed with water (2×45 mL) and heptane (2×45 mL). The filter cake was dried at 40° C. in vacuo for 16 h to afford tert-butyl (2-(4-acetamidobenzamido) phenyl)carbamate (31.8 g, 78% yield, 90.6% HPLC purity) as a white solid.
Reaction SMILES: C[N:2](C)/[CH:3]=[CH:4]\[C:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1)=O.O.[NH2:15]N>C(O)C>[NH:2]1[CH:3]=[CH:4][C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)=[N:15]1
Reactant: CN(C)/C=C\C(=O)c1ccccn1
Reactant: NN
Solvent: O
Solvent: CCO
Product: c1ccc(-c2cc[nH]n2)nc1
Temperature: 25 °C
Yield: 97.3 %

Procedure:
Compound 16a (1 g, 6.2 mmol) obtained from the aforesaid process and hydrazine hydrate (2 mL) were dissolved in ethanol (3.3 mL), and reacted at 60° C. for 0.5 hour. Then, the mixture was cooled to room temperature, and then the solvent was removed in vacuum to afford the product 17a (874.7 mg) as a faint yellow solid, with a yield of 97.3%.
Reaction SMILES: [CH2:1]([N:8]1[C:12]2[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[C:18]([NH:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[N:26]([CH2:30][CH2:31][CH2:32]Cl)[CH:25]=[CH:24]2)=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:34]1[CH:38]=[N:37][N:36]=[N:35]1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>C(OCC)(=O)C.CCCCCC.O.CN(C)C=O>[CH2:1]([N:8]1[C:12]2[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:11]=2[N:10]=[C:9]1[C:18]([NH:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[N:26]([CH2:30][CH2:31][CH2:32][N:34]1[CH:38]=[N:37][N:36]=[N:35]1)[CH:25]=[CH:24]2)=[O:19])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: c1nnn[nH]1
Reactant: O=C(Nc1ccc2c(ccn2CCCCl)c1)c1nc2ccc(Cl)cc2n1Cc1ccccc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: O=C(Nc1ccc2c(ccn2CCCn2cnnn2)c1)c1nc2ccc(Cl)cc2n1Cc1ccccc1
Temperature: 100 °C
Reaction time: 48 h
Yield: 27 %

Procedure:
To 3.8 g of 1-benzyl-6-chloro-2-[1-(3-chloro-propyl)indol-5-ylaminocarbonyl]benzimidazole was added 100 mg of dimethylformamide, further added 1.4 g of 1H-1,2,3,4-tetrazol, 2.2 g of potassium carbonate and 7.2 g of sodium iodide, the mixture was heated and stirred at 100° C. for 2 days. Water was added to the reaction mixture, and extracted with ethyl acetate, the extract was washed with water and an aqueous solution saturated with sodium chloride. The washed extract was dried with anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The residue thus obtained was subjected to a silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/1), after separation of isomers, there were obtained 1.1 g of 1-benzyl-6-chloro-2-{1-[3-(1,2,3,4-tetrazol-1-yl)propyl]indol-5-ylaminocarbonyl}benzimidazole (A) as in form of colorless needle crystals by recrystallization from ethyl acetate-n-hexane, and 0.9 g of 1-benzyl-6-chloro-2-{1-[3-(1,2,3,4-tetrazol-2-yl)-propyl]indol-5-ylaminocarbonyl}benzimidazole (B) as in the form of pale yellow needle crystals by recrystallization from dichloromethane-n-hexane.
Reaction SMILES: [CH3:1][SiH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[CH2:13]=[CH:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Rh]>[CH3:1][Si:2]([CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCC[SiH2]C
Reactant: C=CCCCCCCCC
Agent: [Rh]
Agent: [Cl-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CCCCCCCCCC[Si](C)(CCCCCCCCCC)CCCCCCCCCC
Yield: 80 %

Procedure:
A mixture of 75 grams of methyldecylsilane and 202 grams 1-decene was reacted in the presence of 0.0040 grams of chlorotris(triphenylphosphine)rhodium(I) at 87°-95° C. for one hour. The unreacted decene was stripped off under high vacuum and the residue hydrogenated as above. Distillation gave an 80 percent yield of methyltri(decyl)silane having a boiling point of 230°-233° C. (0.95 mm).
Reaction SMILES: [CH:1]([C:4]1[C:5](=[O:20])[NH:6][C:7](=[O:19])[NH:8][C:9]=1[O:10][C:11]1[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[CH:12]=1)([CH3:3])[CH3:2].C1(C)C=CC(S(O[CH2:31][CH:32]2[CH2:35][CH2:34][CH2:33]2)(=O)=O)=CC=1>>[CH:32]1([CH2:31][N:8]2[C:9]([O:10][C:11]3[CH:12]=[C:13]([CH3:18])[CH:14]=[C:15]([CH3:17])[CH:16]=3)=[C:4]([CH:1]([CH3:3])[CH3:2])[C:5](=[O:20])[NH:6][C:7]2=[O:19])[CH2:35][CH2:34][CH2:33]1
Reactant: Cc1ccc(S(=O)(=O)OCC2CCC2)cc1
Reactant: Cc1cc(C)cc(Oc2[nH]c(=O)[nH]c(=O)c2C(C)C)c1
Product: Cc1cc(C)cc(Oc2c(C(C)C)c(=O)[nH]c(=O)n2CC2CCC2)c1
Yield: 47.9 %

Procedure:
5-Isopropyl-6-(3,5-dimethylphenoxy)-2,4-pyrimidinedione and (cyclobutyl)methyl para-toluenesulfonate were reacted by the same way with the example 1 to obtain the titled compound (164 mg, yield: 47.9%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]2[S:10][CH:11]=[CH:12][CH:13]=2)=[CH:4][CH:3]=1.[I:14]N1C(=O)CCC1=O.C(Cl)(Cl)Cl.C(O)(=O)C>O>[I:14][C:11]1[S:10][C:9]([CH2:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[CH:13][CH:12]=1
Reactant: Fc1ccc(Cc2cccs2)cc1
Reactant: O=C1CCC(=O)N1I
Solvent: CC(=O)O
Solvent: ClC(Cl)Cl
Solvent: O
Product: Fc1ccc(Cc2ccc(I)s2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 95.4 %

Procedure:
A mixture of 2-(4-fluorophenylmethyl)thiophene (3.85 g, 20.0 mmol), prepared as described in step 1, and N-iodosuccinimide (4.50 g, 20.0 mmol) in 1:1 chloroform-acetic acid (40 mL) was stirred at ambient temperature for 1 hour and then diluted with an equal volume of water. The organic layer was washed with saturated aqueous NaHCO3 solution (2×50 mL), 10% aqueous sodium thiosulfate solution (2×50 mL) and once with brine. After drying over MgSO4, the organic layer was concentrated in vacuo to give 6.07 g (95%) of 2-iodo-5-(4-fluorophenylmethyl)thiophene as a gold colored oil.
Reaction SMILES: [CH2:1]([NH:5][NH2:6])[CH2:2][CH2:3][CH3:4].[CH3:7][S:8]([C:11]1[S:15][C:14]([N:16]=[C:17]=[O:18])=[N:13][N:12]=1)(=[O:10])=[O:9].NN>C(Cl)Cl>[CH2:1]([N:5]([C:17]([NH:16][C:14]1[S:15][C:11]([S:8]([CH3:7])(=[O:10])=[O:9])=[N:12][N:13]=1)=[O:18])[NH2:6])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCNN
Reactant: CS(=O)(=O)c1nnc(N=C=O)s1
Agent: NN
Solvent: ClCCl
Product: CCCCN(N)C(=O)Nc1nnc(S(C)(=O)=O)s1
Temperature: 25 °C

Procedure:
A solution of n-butylhydrazine (0.3 mole) in methylene chloride (150 ml) is charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. 5-Methylsulfonyl-1,3,4-thiadiazol-2-yl isocyanate dimer (0.1 mole) is then added, with stirring, at room temperature. After the addition is completed the reaction mixture is heated at reflux for a period of about 4 hours. After this time the reaction mixture is stripped of solvent and excess hydrazine to yield the desired product 2-n-butyl-4-(5-methylsulfonyl-1,3,4-thiadiazol-2-yl)semicarbazide as the residue.
Reaction SMILES: [NH2:1][C:2]1[CH:23]=[CH:22][C:5]([C:6]([N:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[CH2:12][N:11]3[CH:19]=[CH:20][CH:21]=[C:10]3[CH2:9]2)=[O:7])=[CH:4][C:3]=1C.[C:25]1([CH3:34])[C:26]([N:31]=[C:32]=[O:33])=[CH:27][CH:28]=[CH:29][CH:30]=1>O1CCCC1>[CH3:34][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[NH:31][C:32]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=3[CH2:12][N:11]3[CH:19]=[CH:20][CH:21]=[C:10]3[CH2:9]2)=[O:7])=[CH:22][CH:23]=1)=[O:33]
Reactant: Cc1cc(C(=O)N2Cc3cccn3Cc3ccccc32)ccc1N
Reactant: Cc1ccccc1N=C=O
Solvent: C1CCOC1
Product: Cc1ccccc1NC(=O)Nc1ccc(C(=O)N2Cc3cccn3Cc3ccccc32)cc1
Yield: 56.1 %

Procedure:
A mixture of 0.93 g 10,11-dihydro-10-(4-amino-3-methylbenzoyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine and 0.37 g of o-tolyl isocyanate in 50 ml of tetrahydrofuran is heated at reflux under argon for 24 hours. The volatiles are evaporated in vacuo to a residue which is dissolved in methylene chloride and passed through a pad of hydrous magnesium silicate. Hexane is added to the filtrate at the boil to give 0.68 g of the desired product as crystals, m.p. 155-158° C.