Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]([Cl:28])([Cl:27])[CH2:3][O:4][C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13]([O:15]C(C)(C)C)=O)[N:8]1C(OC(C)(C)C)=O)=[O:6].FC(F)(F)C(O)=O.[C:36]([O:40][C:41]([NH:43][C@@H:44]([CH2:48][O:49][CH2:50][C:51]1([CH3:55])[CH2:54][O:53][CH2:52]1)C(O)=O)=[O:42])([CH3:39])([CH3:38])[CH3:37].C(N(CC)C(C)C)(C)C.C[NH3+].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F>ClCCl.C(#N)C.C(OCC)(=O)C>[Cl:28][C:2]([Cl:1])([Cl:27])[CH2:3][O:4][C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][N:9]([C:13](=[O:15])[C@@H:44]([NH:43][C:41]([O:40][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:42])[CH2:48][O:49][CH2:50][C:51]2([CH3:55])[CH2:54][O:53][CH2:52]2)[NH:8]1)=[O:6]
Reactant: CC1(COC[C@H](NC(=O)OC(C)(C)C)C(=O)O)COC1
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H](C(=O)OCC(Cl)(Cl)Cl)N1C(=O)OC(C)(C)C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: C[NH3+]
Agent: F[P-](F)(F)(F)(F)F
Solvent: CC#N
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CC1(COC[C@H](NC(=O)OC(C)(C)C)C(=O)N2CCC[C@@H](C(=O)OCC(Cl)(Cl)Cl)N2)COC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 59.1 %

Procedure:
To (S)-tetrahydro-pyridazine-1,2,3-tricarboxylic acid 1,2-di-tert-butyl ester 3-(2,2,2-trichloro-ethyl)ester (1.76 g, 3.81 mmol) in anhydrous dichloromethane (12 mL) at room temperature and under an atmosphere of nitrogen was added trifluoroacetic acid (12 mL, 152 mmol). The solution was warmed to room temperature and stirred for 16 h. The reaction was concentrated in vacuo and the residue co-evaporated from toluene (3×). The resulting residue was dissolved in anhydrous acetonitrile (5 mL) and added to a solution of (S)-2-tert-butoxycarbonylamino-3-(3-methyl-oxetan-3-ylmethoxy)-propionic acid (1.1 mg, 3.81 mmol), N,N-diisopropylethylamine (2.7 mL, 15.2 mmol) and 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (1.40 g, 3.81 mmol) in anhydrous acetonitrile (20 mL) that had been previously stirred at 0° C. for 20 minutes. The reaction was warmed to room temperature and stirred for 16 h. The reaction was cooled to 0° C. diluted with ethyl acetate and quenched with 1 M hydrochloric acid. The organic layer was separated and washed with a saturated aqueous solution of sodium bicarbonate (2×) and brine (1×). The organic layer was then dried through a hydrophobic frit and concentrated in vacuo. The residue was purified by silica gel chromatography using iso-hexanes/ethyl acetate 1:1 to give the title compound (1.2 g, 59%) as a clear viscous oil. 1H NMR (300 MHz, CDCl3) δ 1.27 (s, 3H), 1.46 (s, 9H), 1.63-2.18 (m, 5H), 3.13-3.27 (m, 1H), 3.45-3.60 (m, 3H), 3.73-3.87 (m, 2H), 4.05-4.17 (m, 1H), 4.38 (d, J=5.6 Hz, 2H), 4.57 (dd, J=7.8, 5.6 Hz, 2H), 4.79 (d, J=11.8 Hz, 1H), 4.91 (d, J=11.8 Hz, 1H), 5.33-5.60 (m, 2H). LCMS (m/z) 532.3 [M+H], Tr=2.75 min.
Reaction SMILES: [CH3:1][C:2]1[C:8]([CH3:9])=[C:7]([OH:10])[C:6]([CH3:11])=[CH:5][C:3]=1[OH:4].C(O)(=O)C.C(C(C)=O)C.[CH2:21]=[CH:22][C:23](=[CH2:25])[CH3:24]>C1(C)C=CC=CC=1.[Cl-].[Zn+2].[Cl-]>[CH3:25][C:23]1([CH3:24])[CH2:22][CH2:21][C:5]2[C:3](=[C:2]([CH3:1])[C:8]([CH3:9])=[C:7]([OH:10])[C:6]=2[CH3:11])[O:4]1
Reactant: C=CC(=C)C
Reactant: Cc1cc(O)c(C)c(C)c1O
Agent: [Cl-]
Agent: [Zn+2]
Solvent: CC(=O)O
Solvent: CCC(C)=O
Solvent: Cc1ccccc1
Product: Cc1c(C)c2c(c(C)c1O)CCC(C)(C)O2
Temperature: 25 °C

Procedure:
In a 50 ml four-necked flask were charged 2,3,5-trimethylhydroquinone (5.0 g), zinc chloride (0.8 g), acetic acid (0.35 ml), methyl ethyl ketone (4 ml) and toluene (15 ml) and the mixture was heated. At 100° C., a solution of isoprene (2.5 g) in toluene (5 ml) was added dropwise under reflux over 2 hr. After the dropwise addition, the mixture was refluxed for 4 more hours and cooled to room temperature. The reaction mixture was transferred to a partition funnel, and, after washing 3 times with 50 ml of water, the solvent was evaporated to give 6.5 g of an oily substance.
Reaction SMILES: [CH2:1]([O:3][C:4]([CH:6]1[CH2:11][NH:10][C:9]2[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=2[O:7]1)=[O:5])[CH3:2].[C:16]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)(=[O:19])[CH:17]=[CH2:18]>O.C1(C)C=CC=CC=1>[CH2:21]([O:20][C:16]([CH2:17][CH2:18][N:10]1[C:9]2[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=2[O:7][CH:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:11]1)=[O:19])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: C=CC(=O)OCc1ccccc1
Reactant: CCOC(=O)C1CNc2ccccc2O1
Solvent: O
Solvent: Cc1ccccc1
Product: CCOC(=O)C1CN(CCC(=O)OCc2ccccc2)c2ccccc2O1

Procedure:
2.3 mmol (0.9 ml) of 40% Triton B in water are added at 0° C. to 22.6 mmol (5 g) of 2-ethoxycarbonyl-3,4-dihydro-2H-1,4-benzoxazine (described in J. Heterocyclic Chem., 1985, 22, 177) and 79 mmol (12.8 g) of benzyl acrylate in 17 ml of toluene. The reaction mixture is refluxed overnight, the solvent is evaporated off and the reaction mixture is heated again for 24 hours. After cooling, hydrolysis and extraction with ethyl acetate, the organic phase is concentrated and purified by chromatography on silica gel using an ethyl acetate/petroleum ether mixture (3/7) as eluant to yield the expected compound.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.Cl[C:7]1[N:8]=[C:9]([NH:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=2)[C:10]2[CH:15]=[C:14]([CH2:16][CH3:17])[S:13][C:11]=2[N:12]=1>>[N:1]1([C:7]2[N:8]=[C:9]([NH:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=3)[C:10]3[CH:15]=[C:14]([CH2:16][CH3:17])[S:13][C:11]=3[N:12]=2)[CH:5]=[CH:4][CH:3]=[N:2]1
Reactant: CCc1cc2c(NCc3ccc(OC)c(OC)c3)nc(Cl)nc2s1
Reactant: c1cn[nH]c1
Product: CCc1cc2c(NCc3ccc(OC)c(OC)c3)nc(-n3cccn3)nc2s1

Procedure:
Following the procedure of Example 97, the reaction of pyrazole with 2-chloro-6-ethyl-4-(3,4-dimethoxybenzylamino)-thieno-[2,3-d]-pyrimidine gives 2-(pyrazol-1-yl)-6-ethyl-4-(3,4-dimethoxybenzylamino)-thieno-[2,3-d]-pyrimidine.
Reaction SMILES: [CH2:1]([N:4]([CH2:21][CH:22]=[CH2:23])[CH:5]1[CH2:9][CH:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[CH2:7][CH:6]1O)[CH:2]=[CH2:3].C([N:26](CC)CC)C.CS(Cl)(=O)=O.[OH-].[NH4+]>CC(OC)(C)C>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][O:10][CH:8]2[CH2:9][CH:5]([N:4]([CH2:21][CH:22]=[CH2:23])[CH2:1][CH:2]=[CH2:3])[CH:6]([NH2:26])[CH2:7]2)=[CH:13][CH:14]=1
Reactant: C=CCN(CC=C)C1CC(OCc2ccc(OC)cc2)CC1O
Reactant: CCN(CC)CC
Agent: CS(=O)(=O)Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: COC(C)(C)C
Product: C=CCN(CC=C)C1CC(OCc2ccc(OC)cc2)CC1N
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a solution of 2-[bis(prop-2-en-1-yl)amino]-4-[(4-methoxyphenyl)methoxy]cyclopentan-1-ol (8.75 g, 27.6 mmol) in dry MTBE (92 ml) at 0° C. under nitrogen was added triethylamine (7.68 ml, 55.1 mmol) and methanesulfonyl chloride (2.58 ml, 33.1 mmol). The reaction mixture was stirred at 0° C. for 30 minutes. To this was then added further triethylamine (7.68 ml, 55.1 mmol) and the reaction was stirred at 0° C. for 30 minutes followed by the addition of ammonium hydroxide (25% aq, 82 ml, 590 mmol). The reaction was warmed to room temperature for 17 hours then partitioned between MTBE and water. The aqueous layer was re-extracted with MTBE. The combined organics were dried over magnesium sulphate, filtered and concentrated in vacuo to afford the title compound.
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.Cl.Cl[CH2:13][CH2:14][N:15]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.[I-].[Na+]>CN(C)C=O.O>[Br:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:13][CH2:14][N:15]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)=[CH:6][CH:5]=1
Reactant: Oc1ccc(Br)cc1
Reactant: ClCCN1CCCCCC1
Agent: Cl
Agent: [H-]
Agent: [I-]
Solvent: O
Solvent: CN(C)C=O
Product: Brc1ccc(OCCN2CCCCCC2)cc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 96.7 %

Procedure:
To a suspension of 60% sodium hydride (1.6 g) in N,N-dimethylformamide (50 ml) was added 4-bromophenol (3.0 g) under a nitrogen atmosphere, the solution was stirred for 10 minutes at room temperature, then 1-(2-chloroethyl)azepane hydrochloride (4.0 g) and sodium iodide (in catalytic amounts) were sequentially added thereto followed by stirring overnight at 80° C. Water was added thereto followed by stirring, the solution was extracted with ethyl acetate, then sequentially washed with water and brine, and the solvent was evaporated in vacuo. The residue was purified by NH silica gel column chromatography (hexane-ethyl acetate system) to provide the title compound (5.0 g).
Reaction SMILES: [CH3:1][C:2]1[CH2:21][S:20][C@@H:5]2[C@H:6]([NH:9][C:10]([C@H:12]([NH2:19])[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[O:11])[C:7](=[O:8])[N:4]2[C:3]=1[C:22]([OH:24])=[O:23].C1C([C@@H](O)[C@H](NC(C(Cl)Cl)=O)CO)=CC=C([N+]([O-])=O)C=1.CCC[C@H]1CN(C)[C@H](C(N[C@H]([C@H](O)C)[C@H]2O[C@H](SC)[C@H](O)[C@@H](O)[C@H]2O)=O)C1.CCC[C@H]1CN(C)[C@H](C(N[C@H]([C@H](O)C)[C@H]2O[C@H](SC)[C@H](O)[C@@H](O)[C@H]2O)=O)C1.O.Cl.C[C@]1(O)[C@@H]2C(=C(O)[C@]3(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]3[C@H]2O)C(=O)C2C(O)=CC=CC1=2.CC1(C)S[C@@H]2[C@H](NC(CC3C=CC=CC=3)=O)C(=O)N2[C@H]1C(O)=O.[Na].[K].CCN(CCOC(C1C=CC(N)=CC=1)=O)CC.CC1(C)S[C@@H]2[C@H](NC(CC3C=CC=CC=3)=O)C(=O)N2[C@H]1C(O)=O.C[C@]1(O)[C@@H]2C(=C(O)[C@]3(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]3C2)C(=O)C2C(O)=CC=CC1=2.CC[C@H]1OC(=O)C[C@@H](O)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)[C@@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@](O)(C)C3)[C@H](N(C)C)[C@H]2O)[C@@H](CC=O)C[C@@H](C)C(=O)C=CC(C)=C[C@@H]1CO[C@@H]1O[C@H](C)[C@@H](O)[C@@H](OC)[C@H]1OC>>[CH3:21][C:2]1([CH3:1])[S:20][C@@H:5]2[C@H:6]([NH:9][C:10]([C@H:12]([NH2:19])[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[O:11])[C:7](=[O:8])[N:4]2[C@H:3]1[C:22]([OH:24])=[O:23]
Reactant: CC1=C(C(=O)O)N2C(=O)[C@@H](NC(=O)[C@H](N)c3ccccc3)[C@H]2SC1
Agent: CC1(C)S[C@@H]2[C@H](NC(=O)Cc3ccccc3)C(=O)N2[C@H]1C(=O)O
Agent: CCC[C@@H]1C[C@@H](C(=O)N[C@@H]([C@H]2O[C@H](SC)[C@H](O)[C@@H](O)[C@H]2O)[C@@H](C)O)N(C)C1
Agent: CCN(CC)CCOC(=O)c1ccc(N)cc1
Solvent: O
Product: CC1(C)S[C@@H]2[C@H](NC(=O)[C@H](N)c3ccccc3)C(=O)N2[C@H]1C(=O)O

Procedure:
Cephalexin; Chloramphenicol; Lincomycin; Lincomycin hydrochloride monohydrate; Oxytetracycline; Penicillin G, sodium or potassium; Procaine penicillin G; Tetracycline; Tylosin.
Reaction SMILES: C[Si](C)(C)[C:3]1[S:4][CH:5]=[CH:6][N:7]=1.[CH2:10]([O:12][C:13](=[O:19])[CH2:14][CH2:15][C:16](Cl)=[O:17])[CH3:11].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:10]([O:12][C:13](=[O:19])[CH2:14][CH2:15][C:16](=[O:17])[C:3]1[S:4][CH:5]=[CH:6][N:7]=1)[CH3:11]
Reactant: C[Si](C)(C)c1nccs1
Reactant: CCOC(=O)CCC(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CCOC(=O)CCC(=O)c1nccs1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred solution of 2-trimethylsilanyl-thiazole (2.6 g, 16.53 mmol) in DCM (30 mL) is added a solution of 3-chlorocarbonyl-propionic acid ethyl ester (5.4 g, 32.81 mmol)in DCM (10 mL). The mixture is stirred overnight at room temperature. To the mixture is added 5% NaHCO3 (30 mL) and mixture is stirred at room temperature for 20 minutes. The organic layer is separated and the aqueous lay is extracted with DCM (2×50 mL). The combined organic layers are dried and the solvent removed. The residue is separated by column (methylene chloride) to give 4-oxo-4-thiazol-2-yl-butyric acid ethyl ester.
Reaction SMILES: [C:1]([O-:4])(=[O:3])[CH3:2].[K+].[C:6]([O-])(=O)C.[Na+].[Na].[K].[C:13]1([CH2:19][C:20]([OH:22])=[O:21])[CH:18]=[CH:17][CH:16]=CC=1>>[C:1]1([C:2]2[C:17](=[CH:18][CH:13]=[C:19]([C:20]([OH:22])=[O:21])[CH:6]=2)[CH2:16][O:4]1)=[O:3]
Reactant: CC(=O)[O-]
Reactant: O=C(O)Cc1ccccc1
Agent: [K+]
Agent: [K]
Agent: [Na+]
Product: O=C(O)c1ccc2c(c1)C(=O)OC2

Procedure:
By this method (schematically shown above) a 2-, 3- or 4- substituted phenylacetic acid (I) is reacted with benzene 1,2,4-tri-carboxylic anhydride (II) in about equimolar amounts at a temperature of about 200° to 280° C. in the presence of a suitable catalyst such as potassium acetate, sodium acetate or the sodium or potassium salt of the phenylacetic acid used. This results in a mixture of 3-(2-, 3- or 4-substituted benzylidene) phthalide-6-carboxylic acid (IIIa) and -5-carboxylic acid (IIIb).
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[N:24]=[N+]=[N-])(=[O:3])[CH3:2].CO>[Pd].C1COCC1>[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[NH2:24])(=[O:3])[CH3:2]
Reactant: CC(=O)OC[C@H]1O[C@@H](N=[N+]=[N-])[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@H]1OC(C)=O
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: CC(=O)OC[C@H]1O[C@@H](N)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@H]1OC(C)=O
Reaction time: 12 h
Yield: 85.9 %

Procedure:
Palladium catalyst (10% on carbon, 20.0 mg) was added in one portion to a solution of 2,3,4,6-tetra-O-acetyl-β-D-galacto-pyranosyl azide (6)(500 mg, 1.34 mmol) in abs. methanol (5 ml) under a hydrogen atmosphere. A small amount of abs. THF was added to dissolve the sugar. The solution was allowed to stir for 12 hours. The catalyst was subsequently filtered off, and the solvent evaporated. Purification by column chromatography gave (11) (400 mg, 86%).
Reaction SMILES: [CH3:1][C:2]([CH3:9])([CH2:6][CH:7]=O)[CH2:3][CH:4]=O.Cl.[NH2:11][CH2:12][CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16].C(N(CC)CC)C>C(Cl)(Cl)Cl>[CH3:1][C:2]1([CH3:9])[CH:6]=[CH:7][N:11]([CH2:12][CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16])[CH:4]=[CH:3]1
Reactant: CC(C)(CC=O)CC=O
Reactant: COC(=O)CCCN
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: COC(=O)CCCN1C=CC(C)(C)C=C1
Temperature: 25 °C
Yield: 26.1 %

Procedure:
Under nitrogen, 5.89 g (0.046 mole) of 3,3-dimethylglutaraldehyde, 7.03 g (0.0457 mole) of methyl 4-aminobutanoate hydrochloride (the compound of Example 9a), and 9 g of 5A molecular sieves were combined in 425 ml of chloroform at room temperature. 7.0 ml (0.05 mole) of triethylamine were added to the reaction mixture before it was warmed to reflux. After 21 hours the reaction mixture was cooled to room temperature, filtered, and the filtrate evaporated in vacuo. The residue was suspended in about 300 ml of ethyl ether and filtered. The filtrate was evaporated in vacuo to yield 8.56 g of crude product. The crude product was distilled to yield 2.5 g of the title compound as a clear liquid, bp 95° C./0.2 mm Hg.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[C:10]=1Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.O.O.O.O.O.O.O.O.[S-2:28].[Na+].[Na+].CCOCC.Cl>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[C:10]=1[SH:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [S-2]
Reactant: O=[N+]([O-])c1cccc(OCc2ccccc2)c1Cl
Agent: Cl
Agent: [Na+]
Solvent: CCOCC
Solvent: O
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1cccc(OCc2ccccc2)c1S
Temperature: 22 °C
Reaction time: 30 h

Procedure:
To a solution of 8.56 g (32.5 mmol) of 1-(benzyloxy)-2-chloro-3-nitrobenzene in 120 mL of DMF was added 15.6 g (64.9 mmol) of pulverized sodium sulfide nonahydrate. The mixture was stirred vigorously at 22° C. for 30 hours and then poured into a vigorously stirred mixture of ether and 1 N HCl. The organic layer was washed with water then brine, dried (Na2SO4), and evaporated. The residue was crystallized from dichloromethane (DCM) and hexane to give 2-(benzyloxy)-6-nitrobenzenethiol.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][NH2:13])[CH:5]=[CH:4][N:3]=[CH:2]1.[Cl:14][C:15]1[C:16]2[C:17]3[C:21](=[C:22]([Cl:24])[CH:23]=1)[N:20]=[C:19](S)[C:18]=3[CH:26]=[CH:27][CH:28]=2.C(O)C.[ClH:32]>CC(C)=O>[ClH:14].[ClH:32].[Cl:14][C:15]1[C:16]2[C:17]3[C:21](=[C:22]([Cl:24])[CH:23]=1)[N:20]=[C:19]([NH:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][N:1]1[CH:5]=[CH:4][N:3]=[CH:2]1)[C:18]=3[CH:26]=[CH:27][CH:28]=2
Reactant: SC1=Nc2c(Cl)cc(Cl)c3cccc1c23
Reactant: NCCCCCCCn1ccnc1
Agent: Cl
Solvent: CCO
Solvent: CC(C)=O
Product: Clc1cc(Cl)c2cccc3c2c1N=C3NCCCCCCCn1ccnc1
Temperature: 25 °C

Procedure:
The free base of the title compound was prepared by the method of Example 55, utilizing 5.4 grams of 7-(1H-imidazol-1-yl)heptanamine, 7.6 grams of 6,8-dichlorobenz(cd)indol-2-thiol, 9.5 grams of mercuric acetate, and 500 ml of ethanol. A solution of 2.5 grams of the free base in 100 ml warm ethanol was treated with 30 ml of 2.3 N ethanolic hydrogen chloride. The resultant mixture was taken to dryness in vacuo, and the residual syrup boiled up in 400 ml of acetone. Cooling at room temperature gave 1.9 grams of the title compound mp 198° C.-201° C.
Reaction SMILES: C(N(CC)CC)C.Cl.[C:9]([O:13][C:14](=[O:17])[CH2:15][NH2:16])([CH3:12])([CH3:11])[CH3:10].[CH:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[CH:20][C:19]=1[S:28](Cl)(=[O:30])=[O:29]>C(Cl)Cl.CCOCC>[C:9]([O:13][C:14](=[O:17])[CH2:15][NH:16][S:28]([C:19]1[CH:20]=[CH:21][C:22]2[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:18]=1)(=[O:30])=[O:29])([CH3:12])([CH3:11])[CH3:10]
Reactant: CC(C)(C)OC(=O)CN
Reactant: O=S(=O)(Cl)c1ccc2ccccc2c1
Agent: Cl
Solvent: CCOCC
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)CNS(=O)(=O)c1ccc2ccccc2c1
Yield: 87.3 %

Procedure:
14.4 ml of triethylamine are added dropwise to 6.91 g of glycine t-butyl ester hydrochloride and 12.1 g of 2-naphthylsulfonyl chloride in 70 ml of methylene chloride. The reaction mixture is subsequently diluted with 200 ml of ether. The organic phase is washed with 1N hydrochloric acid and with water. After drying and evaporation the residue is suspended in ether and suction filtered. After drying the crystals there are obtained 11.57 g of N-(2-naphthylsulfonyl)-glycine t-butyl ester, Rf=0.49 (ether/hexane 2:1).
Reaction SMILES: [N:1]1([C:7]2[N:8]=[C:9]([CH2:14][C:15]([O-])=O)[NH:10][C:11](=[O:13])[CH:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Na+].[CH2:19]([NH:26][C:27]1[C:28]([NH2:33])=[CH:29][CH:30]=[CH:31][CH:32]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl.CN(C)CCCN=C=NCC>N1C=CC=CC=1.CN(C)C=O.C(O)(=O)C>[CH2:19]([N:26]1[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[N:33]=[C:15]1[CH2:14][C:9]1[NH:10][C:11](=[O:13])[CH:12]=[C:7]([N:1]2[CH2:2][CH2:3][O:4][CH2:5][CH2:6]2)[N:8]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: Nc1ccccc1NCc1ccccc1
Reactant: O=C([O-])Cc1nc(N2CCOCC2)cc(=O)[nH]1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: c1ccncc1
Solvent: CC(=O)O
Product: O=c1cc(N2CCOCC2)nc(Cc2nc3ccccc3n2Cc2ccccc2)[nH]1
Yield: 54.2 %

Procedure:
The product is prepared according to the procedure described in Example 3, using 300 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate, 455 mg of N-benzylbenzene-1,2-diamine and 330 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride in a mixture of 2.5 ml of pyridine and 2.5 ml of dimethylformamide and then in 5 ml of acetic acid. After refluxing for forty-five minutes and purification by silica column chromatography, eluent: CH2Cl2/MeOH: 95/05, 250 mg of 2-[(1-benzyl-1H-benzimidazol-2-yl)methyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one are obtained in the form of a cream powder, the characteristics of which are the following:
Reaction SMILES: [CH3:1][C:2]([C:10]1[CH:11]=[CH:12][C:13]([O:18][CH3:19])=[C:14]([CH:17]=1)[CH:15]=O)([CH3:9])[C:3]#[C:4][C:5]([F:8])([F:7])[F:6].[NH2:20][C@H:21]1[CH2:26][CH2:25][CH2:24][N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C@H:22]1[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(OC(N1CCC[C@H](NCC2C=C(C(C(F)(F)F)C(F)(F)F)C=CC=2OC)[C@@H]1C1C=CC=CC=1)=O)(C)(C)C>>[C:30]([O:29][C:27]([N:23]1[CH2:24][CH2:25][CH2:26][C@H:21]([NH:20][CH2:15][C:14]2[CH:17]=[C:10]([C:2]([CH3:9])([CH3:1])[C:3]#[C:4][C:5]([F:8])([F:7])[F:6])[CH:11]=[CH:12][C:13]=2[O:18][CH3:19])[C@@H:22]1[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:28])([CH3:33])([CH3:31])[CH3:32]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H](N)[C@@H]1c1ccccc1
Reactant: COc1ccc(C(C)(C)C#CC(F)(F)F)cc1C=O
Agent: COc1ccc(C(C(F)(F)F)C(F)(F)F)cc1CN[C@H]1CCCN(C(=O)OC(C)(C)C)[C@H]1c1ccccc1
Product: COc1ccc(C(C)(C)C#CC(F)(F)F)cc1CN[C@H]1CCCN(C(=O)OC(C)(C)C)[C@H]1c1ccccc1

Procedure:
This compound was prepared from Compound 58 and Compound 12 in the same manner of Compound 13.
Reaction SMILES: [CH2:1]([N:8]([CH2:24][C@H:25]([OH:47])[CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[C:30]([NH:42][S:43]([CH3:46])(=[O:45])=[O:44])[CH:29]=1)[C@H:9]1[CH2:14][CH2:13][C@H:12]([C:15]2[CH:23]=[CH:22][C:18]([C:19](O)=[O:20])=[CH:17][CH:16]=2)[CH2:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C.[NH2:69][CH2:70][CH2:71][C:72]1[C:80]2[C:75](=[CH:76][CH:77]=[CH:78][CH:79]=2)[NH:74][CH:73]=1>ClCCl.C(#N)C.C(N(CC)CC)C>[CH2:1]([N:8]([CH2:24][C@H:25]([OH:47])[CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)=[C:30]([NH:42][S:43]([CH3:46])(=[O:44])=[O:45])[CH:29]=1)[C@H:9]1[CH2:10][CH2:11][C@H:12]([C:15]2[CH:23]=[CH:22][C:18]([C:19]([NH:69][CH2:70][CH2:71][C:72]3[C:80]4[C:75](=[CH:76][CH:77]=[CH:78][CH:79]=4)[NH:74][CH:73]=3)=[O:20])=[CH:17][CH:16]=2)[CH2:13][CH2:14]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NCCc1c[nH]c2ccccc12
Reactant: CS(=O)(=O)Nc1cc(OC[C@@H](O)CN(Cc2ccccc2)[C@H]2CC[C@H](c3ccc(C(=O)O)cc3)CC2)ccc1OCc1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CC#N
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)Nc1cc(OC[C@@H](O)CN(Cc2ccccc2)[C@H]2CC[C@H](c3ccc(C(=O)NCCc4c[nH]c5ccccc45)cc3)CC2)ccc1OCc1ccccc1
Reaction time: 24 h

Procedure:
A solution of 0.3 g (0.45 mmol) of trans-4-[4-(benzyl{(2S)-3-[4-(benzyloxy)-3-[(methylsulfonyl)amino]phenoxy]-2-hydroxypropyl}amino)cyclohexyl]benzoic acid (preparation 3), of 0.78 g (0.91 mmol) of 1-hydroxybenzotriazole, of 0.175 g (0.91 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, of 0.19 ml of triethylamine and of 0.138 g (0.86 mmol) of tryptamine in a mixture of 4 ml of dichloromethane and 0.8 ml of acetonitrile is stirred for 24 h. The solvents are evaporated under reduced pressure. Dichloromethane and water are added and the organic phase is washed three times with water. The organic phases are dried over magnesium sulfate and concentrated under reduced pressure. The title compound is obtained in the form of a white solid (0.246 g, 58%) after purification on silica gel (eluent: heptane/ethyl acetate 60/40 for 10 min, 60/40 to 40/60 in 10 min and then 40/60 for 20 min gradient). [M+H+]=801.6
Reaction SMILES: [F:1][CH:2]([F:27])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:11][CH:12]=[C:13]([CH2:15][CH2:16][C:17]([C:19]3[C:24]([CH3:25])=[CH:23][CH:22]=[CH:21][N:20]=3)=[O:18])[N:14]=2)=[CH:6][C:5]=1[OH:26].[CH2:28]1[CH2:38]CN2C(=NCCC2)C[CH2:29]1.BrC(C)C.O>C(O)C.C(OCC)(=O)C>[F:27][CH:2]([F:1])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[O:11][CH:12]=[C:13]([CH2:15][CH2:16][C:17]([C:19]3[C:24]([CH3:25])=[CH:23][CH:22]=[CH:21][N:20]=3)=[O:18])[N:14]=2)=[CH:6][C:5]=1[O:26][CH:28]([CH3:38])[CH3:29]
Reactant: C1CCC2=NCCCN2CC1
Reactant: Cc1cccnc1C(=O)CCc1coc(-c2ccc(OC(F)F)c(O)c2)n1
Solvent: CCO
Solvent: CC(C)Br
Solvent: CCOC(C)=O
Product: Cc1cccnc1C(=O)CCc1coc(-c2ccc(OC(F)F)c(OC(C)C)c2)n1
Reaction time: 8 h

Procedure:
A 0.15 g quantity of the compound obtained in Example 327 and 0.18 ml of DBU were dissolved in 3 ml of ethanol, 0.15 g of 2-bromopropane was then added to the obtained solution, and heating and refluxing were conducted overnight. After cooling, water was added to the reaction mixture, and ethyl acetate extraction was performed. The organic layer was washed twice with water, concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=3:1). The obtained crystals were recrystallized from aqueous 80% ethanol, thereby yielding 70 mg of white powdery 3-[2-(4-difluoromethoxy-3-isopropoxyphenyl)oxazol-4-yl]-1-(3-methylpyridin-2-yl)propan-1-one