Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]([CH3:14])([C:4](=[O:13])[CH:5]=[CH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:3].BrBr.[NH:17]1[CH:21]=[N:20][CH:19]=[N:18]1.[H-].[Na+]>C(Cl)(Cl)(Cl)Cl.CN(C)C=O.O>[CH3:3][C:2]([CH3:14])([C:4](=[O:13])[CH:5]=[C:6]([C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)[N:17]1[CH:21]=[N:20][CH:19]=[N:18]1)[CH3:1]
Reactant: c1nc[nH]n1
Reactant: CC(C)(C)C(=O)C=Cc1ccccc1
Agent: BrBr
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)(C)C(=O)C=C(c1ccccc1)n1cncn1

Procedure:
2,2-Dimethyl-5-phenylpent-4-ene-3-one (9.48 g) in carbon tetrachloride (60 ml) was treated dropwise with bromine (8.0 g). The solution was evaporated in a vacuum and the pale yellow residue of 4,5-dibromo-2,2-dimethyl-5-phenylpentan-3-one (12.6 g) collected. The dibromo compound so prepared (6.96 g) was dissolved in dry dimethylformamide (20 ml) and added dropwise to a mixture obtained by adding 1,2,4-triazole (2.76 g) to a suspension of sodium hydride (1.92 of 50% dispersion in mineral oil, washed free of oil with dry petrol) in dimethylformamide (10 ml). The resulting mixture was heated on a steambath for 15 minutes and poured into cold water (200 ml). The mixture was extracted with ether and the ether extracts dried and evaporated to give a pale yellow oil. This oil crystallised from petrol to give 2,2-dimethyl-5-phenyl-5-(1,2,4-triazol-1-yl)pent-4-en-3-one (compound no. 1 of Table I) having a melting point of 70°- 73° C.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[O:13][C:14]([CH3:30])=[C:15]([CH2:17][CH2:18]OS(C3C=CC(C)=CC=3)(=O)=O)[N:16]=2)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4].[CH3:31][CH:32]1[CH2:36][CH2:35][CH2:34][NH:33]1>>[CH2:1]([O:5][C:6]1[CH:7]=[CH:8][C:9]([C:12]2[O:13][C:14]([CH3:30])=[C:15]([CH2:17][CH2:18][N:33]3[CH2:34][CH2:35][CH2:36][CH:32]3[CH3:31])[N:16]=2)=[CH:10][CH:11]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOc1ccc(-c2nc(CCOS(=O)(=O)c3ccc(C)cc3)c(C)o2)cc1
Reactant: CC1CCCN1
Product: CCCCOc1ccc(-c2nc(CCN3CCCC3C)c(C)o2)cc1

Procedure:
Starting with Toluene-4-sulfonic acid 2-[2-(4-butoxy-phenyl)-5-methyl-oxazol-4-yl]-ethyl ester [CAS 478540-91-9] and racemic 2-methylpyrrolidine, follow procedures significantly analogous to Example 8 to provide the free base of the titled compound. The free base is converted to the titled compound significantly in accordance with the procedure of Example 23. MS (m/e): 343.3 (M+1)
Reaction SMILES: Br.[C:2]1([C:8]2[CH2:9][CH2:10][N:11]([CH2:14][CH2:15][CH2:16][CH2:17][N:18]3[C:23]4[CH:24]=[CH:25][CH:26]=[C:27]([N+:28]([O-:30])=[O:29])[C:22]=4[C:21](=O)[O:20]C3=O)[CH2:12][CH:13]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[NH4+:34]>CN(C)C=O>[C:2]1([C:8]2[CH2:9][CH2:10][N:11]([CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:23]3[CH:24]=[CH:25][CH:26]=[C:27]([N+:28]([O-:30])=[O:29])[C:22]=3[C:21]([NH2:34])=[O:20])[CH2:12][CH:13]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [NH4+]
Reactant: O=c1oc(=O)n(CCCCN2CC=C(c3ccccc3)CC2)c2cccc([N+](=O)[O-])c12
Agent: Br
Agent: [OH-]
Solvent: CN(C)C=O
Product: NC(=O)c1c(NCCCCN2CC=C(c3ccccc3)CC2)cccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a suspension of 1-[4-(4-phenyl-1,2,3,6-tetrahydropyridin-1-yl)butyl]-5-nitro-1,2-dihydro-4H-3,1-benzoxazine-2,4-dione hydrobromide (410 mg) in dimethylformamide (4 ml) was added 28% ammonium hydroxide (1 ml) on an ice-bath, and the mixture was stirred for 1 hour at room temperature. The mixture was poured into ice-water, extracted with ethyl acetate, and the extracts were washed with water and brine. After dryness with magnesium sulfate and evaporation of the solvent, 2-[4-(4-phenyl-1,2,3,6-tetrahydropyridin-1-yl)butylamino]-6nitrobenzamide was obtained as an amorphous (300 mg).
Reaction SMILES: [C:1](=[O:34])(OC1C=CC=CC=1)[O:2][CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:15]3[CH:16]=[C:17]([Cl:24])[C:18]([C:20]([F:23])([F:22])[F:21])=[CH:19][C:14]=3[N:13]=[C:12]2[CH2:25][CH3:26])=[CH:7][CH:6]=1.[CH3:35][N:36]1[CH:40]=[C:39]([S:41]([NH2:44])(=[O:43])=[O:42])[N:38]=[CH:37]1>>[Cl:24][C:17]1[C:18]([C:20]([F:21])([F:22])[F:23])=[CH:19][C:14]2[N:13]=[C:12]([CH2:25][CH3:26])[N:11]([C:8]3[CH:7]=[CH:6][C:5]([CH2:4][CH2:3][O:2][C:1](=[O:34])[NH:44][S:41]([C:39]4[N:38]=[CH:37][N:36]([CH3:35])[CH:40]=4)(=[O:43])=[O:42])=[CH:10][CH:9]=3)[C:15]=2[CH:16]=1
Reactant: CCc1nc2cc(C(F)(F)F)c(Cl)cc2n1-c1ccc(CCOC(=O)Oc2ccccc2)cc1
Reactant: Cn1cnc(S(N)(=O)=O)c1
Product: CCc1nc2cc(C(F)(F)F)c(Cl)cc2n1-c1ccc(CCOC(=O)NS(=O)(=O)c2cn(C)cn2)cc1

Procedure:
The title compound was prepared according to the procedure described in step 2 of Example 243 from 2-{4-[6-chloro-2-ethyl-5-(trifluoromethyl)-1H-benzimidazol-1-yl]phenyl}ethyl phenyl carbonate and 1-methyl-1H-imidazol-4-ylsulfonamide.
Reaction SMILES: [CH2:1]([N:19]([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])[CH2:20][CH2:21][CH2:22]O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].CS(Cl)(=O)=O.[CH2:47]([CH2:49][NH2:50])[OH:48]>C(Cl)(Cl)Cl>[OH:48][CH2:47][CH2:49][NH:50][CH2:22][CH2:21][CH2:20][N:19]([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])[CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: NCCO
Reactant: CCCCCCCCCCCCCCCCCCN(CCCO)CCCCCCCCCCCCCCCCCC
Agent: CS(=O)(=O)Cl
Solvent: ClC(Cl)Cl
Product: CCCCCCCCCCCCCCCCCCN(CCCCCCCCCCCCCCCCCC)CCCNCCO

Procedure:
To a stirred solution of N,N-dioctadecyl-3-aminopropanol (1.16 g., 2 mM.) in chloroform (30 ml.) is added methanesulfonyl chloride (0.285 g., 2.5 mM.) and the mixture stirred for seventy-five minutes. Ethanolamine (1.22 g., 20 mM.) is added and the mixture refluxed for forty-five minutes, then cooled and diluted with chloroform (200 ml.). The chloroform solution is washed successively with aqueous sodium hydroxide (5 percent), water and saturated aqueous sodium chloride. It is then dried (Na2SO4) and concentrated to a waxy solid.
Reaction SMILES: C([O:3][C:4](=[O:27])[C:5]([CH3:26])([O:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=1)[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)C.[CH3:28][C:29]1[O:33][C:32]([C:34]2[S:35][CH:36]=[CH:37][CH:38]=2)=[N:31][C:30]=1[CH2:39][CH2:40]OS(C1C=CC(C)=CC=1)(=O)=O.[K+].[Br-]>>[CH3:26][C:5]([O:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:23])[F:24])=[CH:17][CH:16]=1)([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:40][CH2:39][C:30]2[N:31]=[C:32]([C:34]3[S:35][CH:36]=[CH:37][CH:38]=3)[O:33][C:29]=2[CH3:28])=[CH:9][CH:8]=1)[C:4]([OH:3])=[O:27]
Reactant: CCOC(=O)C(C)(Cc1ccc(O)cc1)Oc1ccc(OC(F)(F)F)cc1
Reactant: Cc1ccc(S(=O)(=O)OCCc2nc(-c3cccs3)oc2C)cc1
Agent: [Br-]
Agent: [K+]
Product: Cc1oc(-c2cccs2)nc1CCOc1ccc(CC(C)(Oc2ccc(OC(F)(F)F)cc2)C(=O)O)cc1

Procedure:
The title compound was prepared from 3-(4-hydroxy-phenyl)-2-methyl-2-(4-trifluoromethoxy-phenoxy)-propionic acid ethyl ester and toluene-4-sulfonic acid 2-(5-methyl-2-thiophen-2-yl-oxazol-4-yl)-ethyl ester using the procedure of Example 42. 1H NMR (400 MHz, CDCl3) δ 7.70-7.67 (m, 1H), 7.41 (dd, 1H, J=5.2, 1.2 Hz), 7.17 (d, 2H, J=8.8 Hz), 7.11-7.07 (m, 3H), 6.90 (d, 2H, J=8.8 Hz), 6.83 (d, 2H, J=8.8 Hz), 4.20 (t, 2H, J=6.6 Hz), 3.25 and 3.14 (d of Abq, 2H, J=14.0 Hz), 2.99 (t, 2H, J=6.4 Hz), 2.37 (s, 3H), 1.43 (s, 3H). IR (KBr) 3600, 3000, 1727, 1611, 1504, 1265 cm−1. HRMS (ES+) m/z exact mass calcd for C27H25NO6F3S 548.1354, found 548.1362.
Reaction SMILES: Cl[CH:2]1[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]1.[Mg].[Br:10][C:11]1[CH:18]=[CH:17][C:14]([C:15]#N)=[CH:13][CH:12]=1.[Cl-].[NH4+].[OH2:21]>O1CCCC1>[Br:10][C:11]1[CH:18]=[CH:17][C:14]([C:15]([CH:2]2[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]2)=[O:21])=[CH:13][CH:12]=1
Reactant: O
Reactant: CN1CCC(Cl)CC1
Reactant: N#Cc1ccc(Br)cc1
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CN1CCC(C(=O)c2ccc(Br)cc2)CC1
Reaction time: 1 h

Procedure:
To a stirred and cooled (10°-15° C.) Grignard-complex, previously prepared starting from 13.5 parts of 4-chloro-1-methylpiperidine and 2.4 parts of magnesium in 68 parts of tetrahydrofuran, is added dropwise a solution of 10 parts of 4-bromobenzonitrile in 22 parts of tetrahydrofuran. Upon completion, stirring is continued for 1 hour at reflux temperature. The reaction mixture is decomposed by pouring onto a mixture of 50 parts of ammonium chloride in 250 parts of water. The product is extracted with methylbenzene. The extract is dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions are collected and the eluent is evaporated, yielding 10 parts of (4-bromophenyl)-(1-methyl-4-piperidinyl)methanone as a residue.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].C[O:8][C:9]([C:11]1[CH:35]=[CH:34][C:14]2[C@@H:15]3[C@H:20]([CH2:21][CH2:22][C:13]=2[CH:12]=1)[N:19]([C:23]([C:25]1[CH:33]=[CH:32][C:28]2[NH:29][CH:30]=[N:31][C:27]=2[CH:26]=1)=[O:24])[CH2:18][CH2:17][CH2:16]3)=O.O>O1CCCC1>[NH:29]1[C:28]2[CH:32]=[CH:33][C:25]([C:23]([N:19]3[C@@H:20]4[C@@H:15]([C:14]5[CH:34]=[CH:35][C:11]([CH2:9][OH:8])=[CH:12][C:13]=5[CH2:22][CH2:21]4)[CH2:16][CH2:17][CH2:18]3)=[O:24])=[CH:26][C:27]=2[N:31]=[CH:30]1
Reactant: COC(=O)c1ccc2c(c1)CC[C@H]1[C@@H]2CCCN1C(=O)c1ccc2[nH]cnc2c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: O=C(c1ccc2[nH]cnc2c1)N1CCC[C@@H]2c3ccc(CO)cc3CC[C@@H]21
Temperature: -10 °C
Reaction time: 2 h

Procedure:
Lithium aluminum hydride (1 mol/L in tetrahydrofuran, 0.5 mL) is added to a solution of cis-4-(1H-benzoimidazole-5-carbonyl)-1,2,3,4,4a,5,6,10b-octahydro-benzo[f]quinoline-8-carboxylic acid methyl ester (150 mg) in tetrahydrofuran (6 mL) cooled to −10° C. The resulting solution is stirred for 2 h while warming to ca. −3° C. in the cooling bath. Little water is added carefully and the resulting mixture is filtered over Celite. The filtrate is diluted with ethyl acetate and dried (MgSO4). The solvent is evaporated and the residue is triturated with ethyl acetate and dried to give the title compound as a solid. Yield: 56 mg (40% of theory); LC (method 1): tR=2.03 min; Mass spectrum (ESI+): m/z=362 [M+H]+.
Reaction SMILES: Cl[CH2:2][CH2:3][CH:4]1[CH2:10][N:9]([CH3:11])[C:8](=[O:12])[C:7]2[CH:13]=[CH:14][CH:15]=[N:16][C:6]=2[CH2:5]1.[CH3:17][CH:18]1[CH2:22][CH2:21][CH2:20][NH:19]1>C(O)C>[CH3:17][CH:18]1[CH2:22][CH2:21][CH2:20][N:19]1[CH2:2][CH2:3][CH:4]1[CH2:10][N:9]([CH3:11])[C:8](=[O:12])[C:7]2[CH:13]=[CH:14][CH:15]=[N:16][C:6]=2[CH2:5]1
Reactant: CC1CCCN1
Reactant: CN1CC(CCCl)Cc2ncccc2C1=O
Solvent: CCO
Product: CC1CCCN1CCC1Cc2ncccc2C(=O)N(C)C1

Procedure:
To a solution of 8-(2-chloroethyl)-6,7,8,9-tetrahydro-6-methyl-5H-pyrido[3,2-c]azepin-5-one in ethanol was added 2-methylpyrrolidine. The solution is heated to reflux for several hours and ethanol is removed by evaporation. The residue is partitioned between dilute aqueous base and chloroform and the chloroform layer concentrated and the title compound isolated by an appropriate technique, e.g., distillation.
Reaction SMILES: [NH2:1][C:2]1[N:3]=[C:4]([NH:11][C:12](=[O:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[S:5][C:6]=1[C:7]([O:9]C)=[O:8].O.[OH-].[Li+].Cl>O1CCCC1.O>[NH2:1][C:2]1[N:3]=[C:4]([NH:11][C:12](=[O:19])[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[S:5][C:6]=1[C:7]([OH:9])=[O:8]
Reactant: COC(=O)c1sc(NC(=O)c2ccccc2)nc1N
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Nc1nc(NC(=O)c2ccccc2)sc1C(=O)O
Temperature: 25 °C
Reaction time: 16 h
Yield: 93.3 %

Procedure:
To a solution of methyl 4-amino-2-benzamidothiazole-5-carboxylate (0.16 g, 0.57 mmol) in tetrahydrofuran (10 mL) and water (5 mL) was added lithium hydroxide monohydrate (0.007 g, 1.60 mmol). The reaction mixture was stirred at ambient temperature for 16 hours and adjusted to pH 5˜6 with 5% hydrochloric acid. The mixture was extracted with ethyl acetate (3×100 mL) and the combined organic extract was washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated to afford the title compound (0.14 g, 88%); MS (ES+) m/z 263.4 (M+1).
Reaction SMILES: [C:1]1([CH:11]=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[C:13]1(=[O:20])[CH2:18][CH2:17][CH2:16][C:15](=O)[CH2:14]1.[CH2:21]([O:23][C:24](=[O:29])[CH2:25][C:26](=[NH:28])[NH2:27])[CH3:22].C(O)C.CN(C=O)C>C(O)C>[CH2:21]([O:23][C:24]([C:25]1[CH:11]([C:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:4]=[CH:3][CH:2]=2)[C:14]2[C:13](=[O:20])[CH2:18][CH2:17][CH2:16][C:15]=2[NH:27][C:26]=1[NH2:28])=[O:29])[CH3:22]
Reactant: O=Cc1cccc2ccccc12
Reactant: CCOC(=O)CC(=N)N
Reactant: O=C1CCCC(=O)C1
Solvent: CCO
Solvent: CN(C)C=O
Product: CCOC(=O)C1=C(N)NC2=C(C(=O)CCC2)C1c1cccc2ccccc12
Yield: 64 %

Procedure:
Upon boiling a solution of 6.3 g of 1-naphthaldehyde, 4.5 g of cyclohexane-1,3-dione and 5.2 g of amidinoacetic acid ethyl ester in 150 ml of ethanol for 2 hours, 2-amino-4-(naphth-1-yl)-1,4,5,6,7,8-hexahydro-5-oxoquinoline-3-carboxylic acid ethyl ester of melting point 279°C (ethanol/DMF) is obtained.
Reaction SMILES: [Br:1][CH:2]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[C:3]([OH:5])=[O:4].Cl[C:21]1[CH:26]=[C:25](Cl)[CH:24]=[C:23](Cl)[C:22]=1O.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)(Cl)Cl.ClCCl.CO>[C:21]1([O:4][C:3](=[O:5])[CH:2]([Br:1])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: CCCCCCCCCCCCCCC(Br)C(=O)O
Reactant: Oc1c(Cl)cc(Cl)cc1Cl
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Solvent: CO
Product: CCCCCCCCCCCCCCC(Br)C(=O)Oc1ccccc1
Reaction time: 0.25 h

Procedure:
2-Bromohexadecanoic acid (1 g) was dissolved in dry chloroform (20 ml). After addition of 2,4,6 trichlorophenol (0.558 g), the reaction mixture was placed in an ice bath. Dicyclohexylcarbodiimide (0.736 g) dissolved in dry chloroform (2 ml) was added to the solution. After stirring the solution for 15 minutes in an ice bath, the temperature was adjusted to 20° C. Formation of the product was ascertained by thin layer chromatography on silicic-acid plates with dichloromethane/methanol (10:0.1 v/v) mixture as solvent. The solution was stirred for 24 h at 20° C. and the precipitated urea removed by filtration. The filtrate was washed twice with sodium bicarbonate (0.05M) solution and water. The crude reaction product was purified by liquid chromatography on silica gel using the same solvent system as eluent.
Reaction SMILES: [CH3:1][C:2]1[C:30]([CH3:31])=[CH:29][C:5]2[N:6]([C:19](=[O:28])[CH2:20][N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)[C:7]3[N:18]=[CH:17][CH:16]=[CH:15][C:8]=3[C:9]3[N:10]([C:11](=[O:14])[NH:12][N:13]=3)[C:4]=2[CH:3]=1.[H-].[Na+].[CH3:34][N:35]([CH3:40])[CH2:36][CH2:37][CH2:38]Cl>CN(C)C=O.C1(C)C(C)=CC=CC=1>[CH3:1][C:2]1[C:30]([CH3:31])=[CH:29][C:5]2[N:6]([C:19](=[O:28])[CH2:20][N:21]3[CH2:22][CH2:23][N:24]([CH3:27])[CH2:25][CH2:26]3)[C:7]3[N:18]=[CH:17][CH:16]=[CH:15][C:8]=3[C:9]3[N:10]([C:11](=[O:14])[N:12]([CH2:38][CH2:37][CH2:36][N:35]([CH3:40])[CH3:34])[N:13]=3)[C:4]=2[CH:3]=1
Reactant: CN(C)CCCCl
Reactant: Cc1cc2c(cc1C)-n1c(n[nH]c1=O)-c1cccnc1N2C(=O)CN1CCN(C)CC1
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1C
Solvent: CN(C)C=O
Product: Cc1cc2c(cc1C)-n1c(nn(CCCN(C)C)c1=O)-c1cccnc1N2C(=O)CN1CCN(C)CC1
Reaction time: 22 h

Procedure:
In the manner given in Example 21, to 6,7-dimethyl-2,9-dihydro-9-[(4-methylpiperazino)acetyl]-3H-pyrido[3,2-c]-s-triazolo[4,3-a][1,5]benzodiazepin-3-one in dimethylformamide is added a solution of sodium hydride in mineral oil. The mixture is allowed to react at about 95° C. for 40 minutes and after cooling [3-(dimethylamino)propyl]chloride in xylene is added. The mixture is kept at 95°-100° C. for a period of 22 hours, evaporated and worked up as in example 25 to give 6,7-dimethyl-2,9-dihydro-2-[3-(dimethylamino)propyl]-9-[(4-methylpiperazino)-acetyl]-3-H-pyrido[3,2-c]-s-triazolo[4,3-a][1,5]benzodiazepin-3-one.
Reaction SMILES: [CH3:1][C:2]([CH3:8])([CH2:5][O:6][CH3:7])[CH2:3][OH:4].[CH3:9][Si:10](Cl)([CH3:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[CH3:1][C:2]([CH3:8])([CH2:3][O:4][Si:10]([CH3:17])([CH3:9])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:5][O:6][CH3:7]
Reactant: C[Si](C)(Cl)c1ccccc1
Reactant: COCC(C)(C)CO
Product: COCC(C)(C)CO[Si](C)(C)c1ccccc1

Procedure:
According to the procedure as described in Example 1,2,2-dimethyl-1-methoxy-3-[(dimethylphenylsilyl)oxy]propane was prepared from intermediate 2,2-dimethyl-3-methoxy-1-propanol and reagent dimethylphenylsilyl chloride.
Reaction SMILES: Br[C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[C:9]1([CH3:18])[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.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>[CH3:8][C:7]1[C:2]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[CH3:18])=[N:3][CH:4]=[CH:5][CH:6]=1
Reactant: Cc1ccccc1B(O)O
Reactant: Cc1cccnc1Br
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: [Na+]
Solvent: COCCOC
Solvent: O
Product: Cc1ccccc1-c1ncccc1C
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A mixture of 2-bromo-3-methylpyridine (1.09 g; 6.34 mmol), o-tolylboronic acid (1.29 g; 9.50 mmol), and Pd(PPh3)4 (147 mg; 2 mol %) in DME (30 ml) is stirred for 10 minutes at room temperature. Sodium carbonate (32 ml of 1M solution in water; 32 mmol) is added to this mixture and the mixture is heated for 16 hours at 80° C. The reaction mixture is treated with water and extracted with dichloromethane. The combined extracts are washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue is purified by flash chromatography over silica gel (elution with 20% EtOAc/Hexane) to 3-methyl-2-o-tolyl-pyridine as a yellow oil. 1H NMR(300 MHz, CDCl3) δ 8.51(d, 1H), 7.58(d, 1H), 7.27-7.15(m, 5H), 2.14(s, 3H), 2.10(s, 3H).
Reaction SMILES: [NH:1]1[CH2:14][CH2:13][CH2:12][NH:11][CH2:10][CH2:9][NH:8][CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[C:15](=O)([O-])[O-].[K+].[K+].ClC[CH:23]=[CH:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN(C=O)C>[CH:24]([C:25]1[CH:26]=[CH:27][C:28]([CH2:15][N:1]2[CH2:14][CH2:13][CH2:12][NH:11][CH2:10][CH2:9][NH:8][CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]2)=[CH:29][CH:30]=1)=[CH2:23]
Reactant: C1CNCCNCCCNCCNC1
Reactant: ClCC=Cc1ccccc1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: C=Cc1ccc(CN2CCCNCCNCCCNCC2)cc1
Yield: 91 %

Procedure:
40 g of cyclam (1) (200 mmol) are dissolved in 1 L of DMF at 70° C. 25 g (181 mmol) of potassium carbonate are added to the solution. A solution of 5.9 g (38.7 mmol) of chloromethylstyrene in 500 ml of DMF is added by slow dropwise addition (9 hours) with stirring. The reaction medium is stirred at 70° C. for an additional hour. After returning to ambient temperature, the excess cyclam and potassium carbonate is removed by filtration. The filtrate is evaporated and the residue is then taken up in diethyl ether. After evaporating the solvent, the compound is obtained in the form of a light yellow oil (11.2 g; 35.4 mmol). Yield: 91%.
Reaction SMILES: ClCCCC(C1C=CC(F)=CC=1)C1C=CC(F)=CC=1.Cl[C:21]1[C:36](Cl)=[CH:35][C:24]2[N:25](C3CCNCC3)[C:26](=[O:28])[NH:27][C:23]=2[CH:22]=1.C(=O)([O-])[O-].[Na+].[Na+].CC(C)[CH2:46][C:47](=[O:49])[CH3:48]>O>[CH3:46][CH:47]([O-:49])[CH3:48].[NH:25]1[C:24]2[CH:35]=[CH:36][CH:21]=[CH:22][C:23]=2[NH:27][C:26]1=[O:28]
Reactant: O=c1[nH]c2cc(Cl)c(Cl)cc2n1C1CCNCC1
Reactant: CC(=O)CC(C)C
Agent: Fc1ccc(C(CCCCl)c2ccc(F)cc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: CC(C)[O-]
Product: O=c1[nH]c2ccccc2[nH]1
Temperature: 25 °C

Procedure:
A mixture of 7 parts of 1-chloro-4,4-bis(4-fluorophenyl)-butane, 5.75 parts of 5,6-dichloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one, 8 parts of sodium carbonate and 100 parts of 4-methyl-2-pentanone is stirred and refluxed for 12 hours with water-separator. The reaction mixture is cooled to room temperature and water is added. The organic layer is separated, dried, filtered and evaporated. The oily residue is purified by column-chromatography over silicagel, using a mixture of trichloromethane and 10% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The solid residue is crystallized successively: once from 4-methyl-2-pentanone and twice from 2-propanol, yielding 5,6-dichloro-1{1-8 4,4-bis(4-fluorophenyl)butyl]-4-piperidinyl}-1,3 -dihydro-2H-benzimidazol-2-one 2-propanolate; mp. 182.5-184.2° C.
Reaction SMILES: [H-].[Na+].O[CH:4]([CH:6]1[CH2:9][CH2:8][CH2:7]1)[OH:5].[NH2:10][C:11]1[N:16]=[C:15](Cl)[CH:14]=[C:13]([Cl:18])[N:12]=1.[O:19]1CCOC[CH2:20]1>>[NH2:10][C:11]1[N:16]=[C:15]([O:5][CH2:4][C:6]2([CH2:20][OH:19])[CH2:9][CH2:8][CH2:7]2)[CH:14]=[C:13]([Cl:18])[N:12]=1
Reactant: OC(O)C1CCC1
Reactant: C1COCCO1
Reactant: Nc1nc(Cl)cc(Cl)n1
Agent: [H-]
Agent: [Na+]
Product: Nc1nc(Cl)cc(OCC2(CO)CCC2)n1
Temperature: 65 °C
Reaction time: 0.5 h
Yield: 50.8 %

Procedure:
60% Sodium hydride (0.4 g, 0.01 mol) was suspended in dry dioxane (40 ml) and dihydroxymethylcyclobutane (1.16 g, 0.01 mol) dissolved in dry dioxane (40 ml) was dropwise added thereto. The mixture was stirred at 60-70° C. for 30 minutes, and 2-amino-4,6-dichloropyrimidine (1.64 g, 0.01 mol) was added. The mixture was refluxed for 3 hours, and filtrated. The solvent in the filtrate was distilled away under reduced pressure and the residue was purified by silica gel column chromatography (chloroform:methanol=50:1) to give white crystals (1.24 g, 50.8%), m.p. 125-127° C. (acetone).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[OH:9])=[CH:4][CH:3]=1.[CH3:23][O:24][C:25](=[O:37])[C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][CH2:35]Cl)=[CH:28][CH:27]=1.[C:38](=[O:41])([O-:40])[O-].[Na+].[Na+].[I-].[K+]>CN(C)C=O>[C:25]([OH:37])(=[O:24])/[CH:26]=[CH:27]/[C:38]([OH:40])=[O:41].[CH3:23][O:24][C:25](=[O:37])[C:26]1[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][CH2:35][N:13]2[CH2:12][CH2:11][CH:10]([C:8]([C:16]3[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=3)([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[OH:9])[CH2:15][CH2:14]2)=[CH:28][CH:27]=1
Reactant: OC(c1ccc(F)cc1)(c1ccc(F)cc1)C1CCNCC1
Reactant: O=C([O-])[O-]
Reactant: COC(=O)c1ccc(OCCCCl)cc1
Agent: [I-]
Agent: [K+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(OCCCN2CCC(C(O)(c3ccc(F)cc3)c3ccc(F)cc3)CC2)cc1
Product: O=C(O)/C=C/C(=O)O
Temperature: 0 °C
Yield: 136.2 %

Procedure:
A mixture of 9.1 g (0.03 mole) of α, α-bis(p-fluorophenyl)-4-piperidinemethanol, 6.7 g (0.03 mole) of 4-(3-chloropropoxy)benzoic acid methyl ester, 10.6 g (0.1 mole) of anhydrous sodium carbonate and 0.6 g of potassium iodide in 125 ml of dimethylformamide was heated in a steambath for 25 hr. The reaction mixture was poured into 1.5 liters of ice-water. The resulting solid was collected by filtration, washed with water and dried. The solid was converted to the fumaric acid salt to yield 12.5 g (68%) of title compound as a white solid, mp 140°-174° C. with decomposition.