Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH2:3][C@H:2]1[C:4]1[CH:5]=[CH:6][C:7]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:8]([NH:10][CH:11]=[O:12])[CH:9]=1.[CH2:21]([NH:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>>[C:22]1([CH2:21][N:28]([CH2:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:3][C@@H:2]([C:4]2[CH:5]=[CH:6][C:7]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[C:8]([NH:10][CH:11]=[O:12])[CH:9]=2)[OH:1])[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: O=CNc1cc([C@@H]2CO2)ccc1OCc1ccccc1
Reactant: c1ccc(CNCc2ccccc2)cc1
Product: O=CNc1cc([C@@H](O)CN(Cc2ccccc2)Cc2ccccc2)ccc1OCc1ccccc1

Procedure:
A mixture of {5-[(2R)-2-oxiranyl]-2-[(phenylmethyl)oxy]phenyl}formamide (WO 0276933) (200 mg) and dibenzylamine (0.75 ml) were heated in a microwave oven at 150° for 30 min. The mixture was allowed to cool to 20° and was purified on a silica SPE bond elut cartridge (10 g) using a gradient of 0% to 50% EtOAc in cyclohexane (Gradmaster™). The appropriate fractions were evaporated in vacuo and the residue further purified by mass-directed autopreparative HPLC to give the title compound (123 mg). LCMS RT=2.75 min.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[NH2:5][C:6]1[S:7][C:8]([S:11][CH2:12][C:13]([CH3:18])([CH3:17])[C:14](O)=[O:15])=[CH:9][N:10]=1>C(O)C>[CH2:1]([O:3][C:14](=[O:15])[C:13]([CH3:17])([CH3:18])[CH2:12][S:11][C:8]1[S:7][C:6]([NH2:5])=[N:10][CH:9]=1)[CH3:2]
Reactant: CC(C)(CSc1cnc(N)s1)C(=O)O
Reactant: CC(=O)Cl
Solvent: CCO
Product: CCOC(=O)C(C)(C)CSc1cnc(N)s1
Reaction time: 0.5 h

Procedure:
Acetyl chloride (3.0 eq) was added drop wise to ethanol and stirred for additionally 30 min after completed addition. 3-(2-Amino-thiazol-5-ylsulfanyl)-2,2-dimethyl-propionic acid was added neat to this solution and the mixture was stirred at 50° C. for 18 h. The mixture was concentrated under reduced pressure and diluted with ethyl acetate and water. The strongly acidic solution was added NaHCO3 (aq; sat) to pH=8. The phases were separated and the aqueous phase extracted with additional ethyl acetate. The combined org. phases were washed with water and brine, dried (MgSO4), filtered and evaporated under reduced pressure to give 3-(2-amino-thiazol-5-ylsulfanyl)-2,2-dimethyl-propionic acid ethyl ester as brown crystals.
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:8][O:9][C:10]=2[CH3:11])[N:3]=[CH:2]1.[Br:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][CH:24]=1>>[Br:18][C:19]1[CH:24]=[C:23]([N:1]2[CH:5]=[C:4]([C:6]3[C:7]([C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=4)=[N:8][O:9][C:10]=3[CH3:11])[N:3]=[CH:2]2)[CH:22]=[CH:21][CH:20]=1
Reactant: OB(O)c1cccc(Br)c1
Reactant: Cc1onc(-c2ccccc2)c1-c1c[nH]cn1
Product: Cc1onc(-c2ccccc2)c1-c1cn(-c2cccc(Br)c2)cn1
Yield: 35 %

Procedure:
As described for Example 3, 4-(1H-imidazol-4-yl)-5-methyl-3-phenyl-isoxazole (112.6 mg, 0.5 mmol) was converted, using 3-bromophenylboronic acid instead of 4-fluorophenylboronic acid, to the title compound (66 mg, 35%) which was obtained as a white solid. MS (ESI): m/e=379.9 [M+H]+.
Reaction SMILES: [CH2:1]([C:4]([CH:13]([C:26]1[CH:31]=[CH:30][C:29](OC)=[CH:28][CH:27]=1)[CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1[NH2:25])([C:9](OC)=[O:10])[C:5]([O:7][CH3:8])=[O:6])[CH:2]=[CH2:3].C[O-].[Na+].CN(C)[CH:39]=[O:40].Cl>CO>[CH3:8][O:7][C:5]([C:4]1([CH2:1][CH:2]=[CH2:3])[CH:13]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:31]=2[O:40][CH3:39])[CH2:14][C:15]2[CH:20]=[C:19]([C:21]([F:23])([F:24])[F:22])[CH:18]=[CH:17][C:16]=2[NH:25][C:9]1=[O:10])=[O:6]
Reactant: C=CCC(C(=O)OC)(C(=O)OC)C(Cc1cc(C(F)(F)F)ccc1N)c1ccc(OC)cc1
Reactant: CN(C)C=O
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: C=CCC1(C(=O)OC)C(=O)Nc2ccc(C(F)(F)F)cc2CC1c1ccccc1OC

Procedure:
α-(2-Propenyl)-[2-(2-amino-5-trifluoromethylphenyl)-1-(4-methoxyphenyl)ethyl]propanedioic acid, dimethyl ester (47.47 g; 0.102 mole) and a 25% (by weight) solution of sodium methoxide in methanol (107 ml; 0.469 mole; d=0.945; 4.6 eq.) in methanol (200 ml) and dry dimethylformamide (200 ml) was refluxed (~95° C.) overnight. 1N Hydrochloric acid was added with stirring, producing a precipitate that was collected by suction-filtration and triturated with water (two times). The solid was slurried in carbon tetrachloride and rotary evaporated followed by vacuum drying to give 42.99 g of crude product.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=[CH2:8])([O-:3])=[O:2].Br[C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1.C(=O)(O)[O-].[Na+]>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N+:1]([C:4]1[CH:5]=[C:6](/[CH:7]=[CH:8]/[C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[CH:9]=[CH:10][CH:11]=1)([O-:3])=[O:2]
Reactant: C=Cc1cccc([N+](=O)[O-])c1
Reactant: Brc1cccnc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1cccc(/C=C/c2cccnc2)c1
Temperature: 110 °C
Reaction time: 3 h

Procedure:
A mixture of 3-nitrostyrene (4.6 ml), 3-bromopyridine (2.6 ml), palladium(II) acetate (0.20 g), tetrabutylammonium chloride (8.4 g) and sodium bicarbonate (6.3 g) in N,N-dimethylformamide (40 ml) was stirred at 110° C. for 3 hours. Then the mixture was poured into aqueous sodium bicarbonate and extracted with ethyl acetate twice. The combined organic phase was washed with aqueous sodium bicarbonate and brine, dried over magnesium sulfate and concentrated. The resultant solid was collected and washed with isoprbpyl ether to give 3-[(E)-2-(3-nitrophenyl)vinyl]pyridine (5.34 g).
Reaction SMILES: [OH:1][C@H:2]1[CH:6]=[CH:5][C@@H:4]([O:7][Si:8]([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9])[CH2:3]1>CCOC(C)=O.CCCCCC>[O:7]([C@H:4]1[CH:5]=[CH:6][C@H:2]([OH:1])[CH2:3]1)[Si:8]([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9]
Reactant: CC(C)(C)[Si](C)(C)O[C@@H]1C=C[C@H](O)C1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CC(C)(C)[Si](C)(C)O[C@H]1C=C[C@H](O)C1
Yield: 81 %

Procedure:
Compound 14 was subjected to general procedure J. Yield=81%. TLC: Rf=0.50 (10% EtOAc/Hexane). 1H NMR (400 MHz, CDCl3): δ0.05 (s, 6H), 0.90 (s, 9H), 2.20 (m, 1H), 2.30 (m, 1H), 5.10 (s, 1H), 6.05 (m, 2H), 6.10 (m, 1H), 8.20 (d, 2H), 8.20 (d, 2H). Subsequent subjection of the product to general procedure E gave compound 22. Yield=85%. TLC: Rf=0.33 (25% EtOAc/Hexane). 1H NMR (400 MHz, CDCl3): δ0.05 (s, 6H), 0.90 (s, 9H), 2.05 (m, 2H), 5.00 (m, 1H), 5.05 (m, 1H), 5.95 (m, 2H).
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:6]=[C:7]([CH:12]=[CH:13][CH:14]=1)[C:8](OC)=[O:9])(=[O:4])=[O:3].[NH2:15][NH2:16]>CO>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]([CH:12]=[CH:13][CH:14]=1)[C:8]([NH:15][NH2:16])=[O:9])(=[O:4])=[O:3]
Reactant: COC(=O)c1cccc(S(C)(=O)=O)c1
Reactant: NN
Solvent: CO
Product: CS(=O)(=O)c1cccc(C(=O)NN)c1
Temperature: 70 °C
Yield: 80 %

Procedure:
Methyl 3-(methylsulfonyl)benzoate (100 mg, 0.467 mmol) was added to hydrazine (22.44 mg, 0.700 mmol)) in methanol (10 mL) and refluxed for 12 h at 70° C. The reaction was monitored by TLC. Upon completion of the reaction and following cooling, the solvent was removed by vacuum, and the compound was purified by flash column chromatography (3% CH3OH/CH2Cl2) affording the title compound (80 mg, 80% yield) as a solid. 1H NMR (400 MHz, CDCl3): δ 8.28 (s, 1H), 8.07 (d, 1H, J=7.6 Hz), 8.01 (d, 1H, J=7.6 Hz), 7.62 (t, 1H, J=7.6 Hz), 3.04 (5, 3H). ESI-MS: 215.1 [M+H]+.
Reaction SMILES: [OH-].[NH4+:2].[CH3:3][N:4]([N:6]=[N:7][C:8]1[C:16]2[C:11](=[N:12][CH:13]=[CH:14][CH:15]=2)[Se:10][C:9]=1[C:17]([O:19]CC)=O)[CH3:5].O>C1COCC1>[CH3:3][N:4]([N:6]=[N:7][C:8]1[C:16]2[C:11](=[N:12][CH:13]=[CH:14][CH:15]=2)[Se:10][C:9]=1[C:17]([NH2:2])=[O:19])[CH3:5]
Reactant: [NH4+]
Reactant: CCOC(=O)c1[se]c2ncccc2c1N=NN(C)C
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CN(C)N=Nc1c(C(N)=O)[se]c2ncccc12
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To an ice cold (0-5° C.) solution of ammonium hydroxide (15 mL) was added a solution of ethyl 3-[(dimethylamino)diazenyl]selenopheno[2,3-b]pyridine-2-carboxylate (150 mg) in THF (5 mL) for 5 min and stirred at rt for 16 h. The solution was poured into ice cooled water and extracted with ethyl acetate (3×100 mL). The combined EtOAc layer was washed with water, brine and dried over sodium sulfate. The solution was filtered and evaporated the solvent. The residue was chromatographed over silica gel column using chloroform-methanol (95:5) as eluents to give the product as a light green color solid, which was recrystallized from chloroform-methanol-hexane (25 mg, 20%), mp 230-232° C. IR (Neat) νmax 3327, 3152, 2913, 1701, 1634, 1360, 1330, 1104, 1058, 1016, 878, 802 cm−1; 1H NMR (400 MHz, DMSO-d6): δ 8.80 (1H, d, J=8.4 Hz, H-4), 8.59 (1H, d, J=3.2 Hz, H-6), 8.18 (1H, s, —CONH2), 7.99 (1H, s, —CONH2), 7.46 (1H, dd, J=8.2, 4.6 Hz, H-5), 3.66 (3H, s, —NCH3), 3.26 (3H, s, —NCH3); 13C NMR (100 MHz, DMSO-d6): δ 164.4, 161.1, 148.3, 142.5, 136.2, 131.5, 130.4, 120.6, 43.6, 36.5; LC-MS (positive ion mode): m/z 318, 320 (M+Na)+.
Reaction SMILES: [C:1]([CH2:3][CH2:4][C:5]1([CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([N:19]([C:27]3[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][N:28]=3)[C:20]([C:22]3[O:23][CH:24]=[CH:25][CH:26]=3)=[O:21])[CH2:15][CH2:14]2)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1)#[N:2].C[Si]([N:38]=[N+:39]=[N-:40])(C)C.C([Sn](=O)CCCC)CCC>C1(C)C=CC=CC=1>[NH:38]1[C:1]([CH2:3][CH2:4][C:5]2([CH2:11][CH2:12][N:13]3[CH2:18][CH2:17][CH:16]([N:19]([C:27]4[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][N:28]=4)[C:20]([C:22]4[O:23][CH:24]=[CH:25][CH:26]=4)=[O:21])[CH2:15][CH2:14]3)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]2)=[N:2][N:40]=[N:39]1
Reactant: Cc1ccc(N(C(=O)c2ccco2)C2CCN(CCC3(CCC#N)CCCCC3)CC2)nc1
Reactant: C[Si](C)(C)N=[N+]=[N-]
Agent: CCCC[Sn](=O)CCCC
Solvent: Cc1ccccc1
Product: Cc1ccc(N(C(=O)c2ccco2)C2CCN(CCC3(CCc4nnn[nH]4)CCCCC3)CC2)nc1

Procedure:
To a solution of N-[1-[2-[1-(2-cyanoethyl)cyclohexyl]ethyl]piperidin-4-yl]-N-(5-methylpyridin-2-yl) -2-furancarboxamide (355 mg) dissolved in toluene (2 mL) were added trimethylsilylazide (0.21 mL) and di-n-butyltin oxide (19.7 mg). The solution was heated under reflux for 11 hours. Trimethylsilylazide (0.42 mL) and di-n-butyltin oxide (98.0 mg) were further added to the solution and it was heated under reflux for 4 hours. The solvent was distilled off under reduced pressure (by azeotropic distillation with methanol). The resulting residue was purified by chromatography (silica gel, chloroform:methanol=80:20) to give the title compound (385 mg).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][N:5]1[C:9]([CH2:10][O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:8][S:7][C:6]1=[N:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][N:21]=1.NCCCN1C(COCC2C=CC=CC=2)=CSC1=NC1C=CC(OC(F)(F)F)=CC=1.[ClH:58]>>[NH2:1][CH2:2][CH2:3][CH2:4][N:5]1[C:9]([CH2:10][O:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([Cl:58])=[CH:15][CH:14]=2)=[CH:8][S:7][C:6]1=[N:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][N:21]=1
Reactant: COc1ccc(N=c2scc(COCc3ccccc3)n2CCCN)nc1
Reactant: Cl
Agent: NCCCn1c(COCc2ccccc2)csc1=Nc1ccc(OC(F)(F)F)cc1
Product: COc1ccc(N=c2scc(COCc3ccc(Cl)cc3)n2CCCN)nc1

Procedure:
The compound (276 mg) obtained in Example 210 (1) was treated in a similar manner to in Example 208 (3), (4) to give the title compound (92 mg) as hydrochloride.
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[C@H:13]([CH2:14][O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH2:12][C@@H:11]([O:23][C:24]2[CH:29]=[C:28](Cl)[N:27]=[CH:26][N:25]=2)[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH2:31]([Mg]Br)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C1COCC1>[CH2:31]([C:28]1[CH:29]=[C:24]([O:23][C@@H:11]2[CH2:12][C@@H:13]([CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3])[C@@H:14]([O:15][Si:16]([C:19]([CH3:20])([CH3:21])[CH3:22])([CH3:18])[CH3:17])[CH2:10]2)[N:25]=[CH:26][N:27]=1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1
Reactant: CC(C)(C)[Si](C)(C)OC[C@@H]1C[C@@H](Oc2cc(Cl)ncn2)C[C@@H]1O[Si](C)(C)C(C)(C)C
Reactant: Br[Mg]Cc1ccccc1
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)OC[C@@H]1C[C@@H](Oc2cc(Cc3ccccc3)ncn2)C[C@@H]1O[Si](C)(C)C(C)(C)C
Reaction time: 8 h

Procedure:
To a solution of 4-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentyl]oxy}-6-chloropyrimidine (0.264 g, 0.559 mmol) and ferric acetylacetonate (0.0395 g, 0.112 mmol) in THF (9 mL) was added a 1.00 M solution of benzylmagnesium bromide in THF (2.52 mL) and the mixture was stirred overnight. The reaction was quenched using NH4Cl and extracted with EtOAc (3×). The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography (0 to 15% EtOAc/hexanes) to afford the title compound as a clear oil. (0.254 g, 86%).
Reaction SMILES: C([N:14]1[CH2:17][CH:16]([O:18][C:19]2[CH:24]=[C:23]([CH2:25][NH:26][C:27]3[N:45]=[CH:44][CH:43]=[CH:42][C:28]=3[C:29]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([C:38]([CH3:41])([CH3:40])[CH3:39])=[CH:34][CH:33]=3)=[O:30])[CH:22]=[CH:21][N:20]=2)[CH2:15]1)(C1C=CC=CC=1)C1C=CC=CC=1.[SiH](CC)(CC)CC.C(O)(C(F)(F)F)=O>>[NH:14]1[CH2:15][CH:16]([O:18][C:19]2[CH:24]=[C:23]([CH2:25][NH:26][C:27]3[N:45]=[CH:44][CH:43]=[CH:42][C:28]=3[C:29]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([C:38]([CH3:41])([CH3:40])[CH3:39])=[CH:34][CH:33]=3)=[O:30])[CH:22]=[CH:21][N:20]=2)[CH2:17]1
Reactant: CC(C)(C)c1ccc(NC(=O)c2cccnc2NCc2ccnc(OC3CN(C(c4ccccc4)c4ccccc4)C3)c2)cc1
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(C)c1ccc(NC(=O)c2cccnc2NCc2ccnc(OC3CNC3)c2)cc1

Procedure:
2-{[2-(1-Benzhydryl-azetidin-3-yloxy)-pyridin-4-ylmethyl]-amino}-N-(4-tert-butyl-phenyl)-nicotinamide (210 mg) was heated at reflux with Et3SiH (5 ml) and TFA (15 ml) for 9 h. The mixture was concentrated, then diluted with CH2Cl2 (50 ml) and washed with sat'd NaHCO3 (50 ml) and brine (30 ml), dried over MgSO4 and purified by silica gel chromatography (10% MeOH/2M NH3 90% EtOAc) to afford the product as a yellow solid. M+H Calc'd for C25H29N5O2: 431.2.
Reaction SMILES: C([N:4]1[C:16]2[CH:15]=[C:14](I)[CH:13]=[CH:12][C:11]=2[C:10]2[C:5]1=[CH:6][C:7](I)=[CH:8][CH:9]=2)(=O)C.[CH:19]1[C:31]2[NH:30][C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23]=2[CH:22]=[CH:21][CH:20]=1>[Cu]=O>[C:15]1([C:20]2[CH:21]=[CH:22][C:23]3[C:24]4[C:29](=[CH:28][C:27]([C:6]5[C:5]6[NH:4][C:16]7[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=7)[C:10]=6[CH:9]=[CH:8][CH:7]=5)=[CH:26][CH:25]=4)[NH:30][C:31]=3[CH:19]=2)[C:16]2[NH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[C:11]=2[CH:12]=[CH:13][CH:14]=1
Reactant: CC(=O)n1c2cc(I)ccc2c2ccc(I)cc21
Reactant: c1ccc2c(c1)[nH]c1ccccc12
Agent: O=[Cu]
Product: c1ccc2c(c1)[nH]c1c(-c3ccc4c(c3)[nH]c3cc(-c5cccc6c5[nH]c5ccccc56)ccc34)cccc12
Temperature: 170 °C
Yield: 139 %

Procedure:
A mixture of 4.0 g of 9-acetyl-2,7-diiodocarbazole and 2.2 g of carbazole were stirred together in 20 ml N,N′-dimethylacetamide. To this was added 1.6 g of copper oxide and heated to 170° C. for 24 h. The reaction was quenched with water and the solid was filtered, washed with methanol, and dried under vacuum. The solid (6 g) was then taken up for further deprotection using 1.2 g KOH with THF (6 ml), methanol (12 ml) and water (12 ml) at reflux temperature. The reaction mixture was then extracted using ethyl acetate; and the organic layer was dried over anhydrous sodium sulfate and evaporated to dryness under vacuum. Subsequent silica gel column chromatography using toluene:hexane (1:2) as eluent, yielded 3.0 g of 2,7-dicarbazolylcarbazole.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:22]=[CH:23][C:24]=1[N+:25]([O-])=O)[NH:7][C:8](=[O:21])[C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[CH:11][CH:10]=1)([O-])=O.[CH:28]1([C:31]([N:33]2[CH2:38][CH2:37][N:36]([C:39]3[CH:46]=[CH:45][C:42]([CH:43]=O)=[CH:41][CH:40]=3)[CH2:35][CH2:34]2)=[O:32])[CH2:30][CH2:29]1>>[CH:28]1([C:31]([N:33]2[CH2:34][CH2:35][N:36]([C:39]3[CH:40]=[CH:41][C:42]([C:43]4[NH:25][C:24]5[CH:23]=[CH:22][C:6]([NH:7][C:8](=[O:21])[C:9]6[CH:14]=[CH:13][C:12]([N:15]7[CH2:20][CH2:19][O:18][CH2:17][CH2:16]7)=[CH:11][CH:10]=6)=[CH:5][C:4]=5[N:1]=4)=[CH:45][CH:46]=3)[CH2:37][CH2:38]2)=[O:32])[CH2:29][CH2:30]1
Reactant: O=C(Nc1ccc([N+](=O)[O-])c([N+](=O)[O-])c1)c1ccc(N2CCOCC2)cc1
Reactant: O=Cc1ccc(N2CCN(C(=O)C3CC3)CC2)cc1
Product: O=C(Nc1ccc2[nH]c(-c3ccc(N4CCN(C(=O)C5CC5)CC4)cc3)nc2c1)c1ccc(N2CCOCC2)cc1

Procedure:
Compound 415 was prepared according to the procedure similar to that described in Scheme III from 3,4-dinitro-N-(4-morpholinobenzoyl)aniline and 4-(4-cyclopropanecarbonylpiperazinyl)benzaldehyde. [M+H]+ calcd for C32H34N6O3: 551.27; found: 551.10.
Reaction SMILES: C(OC(=O)C)(=O)C.[CH2:8]([O:10][C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][C:18]=1[O:19][CH2:20][CH3:21])[CH:14]=O)[CH3:9].[C:22]([NH:25][CH2:26][C:27]([OH:29])=[O:28])(=O)[CH3:23].C([O-])(=O)C.[Na+]>O>[CH2:8]([O:10][C:11]1[CH:12]=[C:13]([CH:16]=[CH:17][C:18]=1[O:19][CH2:20][CH3:21])[CH:14]=[C:26]1[C:27](=[O:28])[O:29][C:22]([CH3:23])=[N:25]1)[CH3:9]
Reactant: CCOc1ccc(C=O)cc1OCC
Reactant: CC(=O)NCC(=O)O
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Solvent: O
Product: CCOc1ccc(C=C2N=C(C)OC2=O)cc1OCC
Yield: 45 %

Procedure:
To acetic anhydride (193 ml) are added 3,4-diethoxybenzaldehyde (234.4 g), N-acetylglycine (95.4 g) and sodium acetate (49.5 g), and the mixture is heated under reflux for one hour, and the reaction mixture is allowed to stand for cooling. The reaction mixture is further allowed to stand in a refrigerator overnight, and then thereto is added water. The mixture is extracted with chloroform, and the extract is washed, dried and concentrated. The residue is crystallized from ethanol to give 4-(3,4-diethoxybenzylidene)-2-methyloxazol-5(4H)-one (100.9 g).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:19](=[O:26])[CH2:20][C:21](OCC)=[O:22])[C:5]2[NH:9][C:8]([CH2:10][CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:7][C:6]=2[CH:18]=1.[BH4-].[Na+]>C(O)C>[OH:26][CH:19]([C:4]1[C:5]2[NH:9][C:8]([CH2:10][CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:7][C:6]=2[CH:18]=[C:2]([OH:1])[CH:3]=1)[CH2:20][CH2:21][OH:22]
Reactant: CCOC(=O)CC(=O)c1cc(O)cc2nc(CCc3ccccc3)[nH]c12
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: OCCC(O)c1cc(O)cc2nc(CCc3ccccc3)[nH]c12
Temperature: 25 °C
Reaction time: 2 h
Yield: 95.7 %

Procedure:
To a suspension of Ethyl 3-(6-hydroxy-2-(2-phenylethyl)benzimidazol-4-yl)-3-oxopropanoate (500 mg) obtained in Inventive Example 42 in anhydrous ethanol (10 mL), while cooling in an ice bath, was added sodium borohydride (81 mg), and the mixture was stirred at room temperature for 2 hours. The reaction solution was diluted with ice water (20 mL) and extracted with ethyl acetate. The organic layer was washed with water and brine and dried over anhydrous sodium sulfate, and then the solvent was evaporated under a reduced pressure. The resulting residue was crystallized from ether to obtain the desired compound as colorless crystal (424 mg).
Reaction SMILES: [CH:1]1([O:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[NH:14][C:15](=[O:17])[CH3:16])[CH2:6][CH2:5][CH2:4][CH:3]=[CH:2]1.ClCCl.C(OCC)(=[O:23])C>>[CH:2]12[O:23][CH:3]1[CH2:4][CH2:5][CH2:6][CH:1]2[O:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15](=[O:17])[CH3:16]
Reactant: CCOC(C)=O
Reactant: CC(=O)Nc1ccccc1OC1C=CCCC1
Solvent: ClCCl
Product: CC(=O)Nc1ccccc1OC1CCCC2OC12
Temperature: 25 °C
Reaction time: 8 h
Yield: 73 %

Procedure:
To a solution of N-[2-(2-cyclohexen-1-yloxy)phenyl]acetamide (76 mg, 329 μmol, 1.0 equiv.) in dichloromethane (5 ml) m-chlorobenzoic acid (85 proz.; 121 mg, 559 μmol, 1.7 equiv.) was added at 0° C. Stirring was continued overnight while the reaction mixture was allowed to warm up slowly to room temperature. The heterogenous mixture was diluted with ethyl acetate and washed with sat sodium sulfite, 5% sodium hydroxide and brine. Drying over sodium sulfate, evaporation of the solvent and flash chromatography on silica gel provided 59 mg (73%) of the title compound as a mixture of the diastereoisomers (ratio A:B=trans:cis=5:3 [1H-NMR]).
Reaction SMILES: Cl[C:2]1[C:7]([NH:8][CH:9]=[O:10])=[C:6]([Cl:11])[N:5]=[C:4]([NH:12][CH:13]=[O:14])[N:3]=1.[CH2:15]([O:22][NH2:23])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(N(CC)CC)C>O1CCOCC1>[CH2:15]([O:22][NH:23][C:2]1[N:3]=[C:4]([NH:12][CH:13]=[O:14])[N:5]=[C:6]([Cl:11])[C:7]=1[NH:8][CH:9]=[O:10])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: O=CNc1nc(Cl)c(NC=O)c(Cl)n1
Reactant: NOCc1ccccc1
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: O=CNc1nc(Cl)c(NC=O)c(NOCc2ccccc2)n1
Temperature: 100 °C
Reaction time: 1 h
Yield: 46.1 %

Procedure:
A mixture of 4,6-dichloro-2,5-diformamido-pyrimidine (1.9g, 8.09mmol), benzyloxyamine (1g, 8.13mmol), triethylamine (2ml) and dioxan (20ml) was stirred at 100° C. for 1 hour. The cooled reaction mixture was filtered and the precipitate collected and washed with dioxan (2×5ml). The filtrate and washings were combined and evaporated to a syrup. Column chromatography on silica gel (eluted with chloroform-ethanol, 30:1) afforded the title compound (1.2g, 46%). IR: υmax (KBr) 3242, 1694, 1588, 1472cm-1 ; 1H NMR δH [(CD3)2SO], 4.89 (2H, s, OCH2Ph), 7.4 (5H, m, Ph), 8.15 (1H, s, CHO), 9.18, 9.42 (1H, 2×br.s, D2O exchangeable, NH), 9.25 (1H, br.s, CHO), 10.91 (2H, br.s, D2O exchangeable, 2×NH). m/e (FAB +ve ion, thioglycerol) MH+ 322.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[NH:13][C:12]2[C:14]([OH:21])=[CH:15][CH:16]=[C:17]([C:18]([OH:20])=[O:19])[C:11]=2[N:10]=1.OS(O)(=O)=O.[CH3:27]O>>[CH3:27][O:19][C:18]([C:17]1[C:11]2[N:10]=[C:9]([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[Cl:1])[NH:13][C:12]=2[C:14]([OH:21])=[CH:15][CH:16]=1)=[O:20]
Reactant: CO
Reactant: O=C(O)c1ccc(O)c2[nH]c(-c3ccc(F)cc3Cl)nc12
Agent: O=S(=O)(O)O
Product: COC(=O)c1ccc(O)c2[nH]c(-c3ccc(F)cc3Cl)nc12
Temperature: 25 °C
Yield: 67 %

Procedure:
2-(2-chloro-4-fluoro-phenyl)-7-hydroxy-1H-benzoimidazole-4-carboxylic acid (500 mg, 1.63 mmol) obtained in step 3 was dissolved in methanol, H2SO4 (0.43 ml, 8.15 mmol) was added dropwise thereto and refluxed for 15 hours. The resulting solution was cooled to room temperature, concentrated under a reduced pressure to remove methanol, and the residue was neutralized with NaHCO3. Then, the neutralized residue was extracted with ethyl acetate and concentrated under a reduced pressure to obtain a residue which was purified by silica gel chromatography to obtain the title compound (393 mg, 1.23 mmol) in a yield of 67%.