Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[C:7]([O:9][CH3:10])[N:6]=[C:5]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH:4]=1)=O.[C:19]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)(=[O:21])[CH3:20].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CC(O)=O.C(Cl)Cl>[C:19]([N:22]1[CH2:27][CH2:26][N:25]([CH2:1][C:3]2[CH:8]=[C:7]([O:9][CH3:10])[N:6]=[C:5]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH:4]=2)[CH2:24][CH2:23]1)(=[O:21])[CH3:20]
Reactant: CC(=O)N1CCNCC1
Reactant: COc1cc(C=O)cc(NC(=O)OC(C)(C)C)n1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: COc1cc(CN2CCN(C(C)=O)CC2)cc(NC(=O)OC(C)(C)C)n1

Procedure:
To a solution of tert-butyl 4-formyl-6-methoxypyridin-2-ylcarbamate (15-3, 292 mg, 1.16 mmole) and 1-acetylpiperazine (178 mg, 1.39 mmole) in 2% glacial HOAc in CH2Cl2 (5 mL) was added NaBH(OAc)3 (270 mg, 1.27 mmole) at RT. After 1.5 hr the mixture was quenched with saturated NaHCO3 and extracted with CH2Cl2 (3×). The combined organic layers were dried (MgSO4), filtered, and concentrated. Flash column chromatography (gradient, 0-5% EtOH/EtOAc) gave the titled compound as a white foam. 1H-NMR (500 MHz, CDCl3) δ7.41 (s, 1H), 7.00 (bs, 1H), 6.43 (s, 1H), 3.83 (s, 3H), 3.63 (bs, 2H), 3.46 (bs, 4H), 2.41 (m, 4H), 2.08 (s, 3H), 1.52 (s, 9H); MS (ES) (M+H)+365.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][N:15]([C:18]3[S:19][C:20]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[C:21]([C:23]([OH:25])=O)[N:22]=3)[CH2:14][C@H:13]2[O:31][CH2:32][CH3:33])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8].[CH2:34]([O:36][CH2:37][CH2:38][NH2:39])[CH3:35].CCN=C=NCCCN(C)C.Cl.ON1C2C=CC=CC=2N=N1>>[Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:11][C@H:12]2[CH2:17][CH2:16][N:15]([C:18]3[S:19][C:20]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[C:21]([C:23](=[O:25])[NH:39][CH2:38][CH2:37][O:36][CH2:34][CH3:35])[N:22]=3)[CH2:14][C@H:13]2[O:31][CH2:32][CH3:33])=[O:10])[NH:5][C:6]=1[CH2:7][CH3:8]
Reactant: CCOC(=O)c1sc(N2CC[C@H](NC(=O)c3nc(Cl)c(CC)[nH]3)[C@H](OCC)C2)nc1C(=O)O
Reactant: CCOCCN
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Product: CCOCCNC(=O)c1nc(N2CC[C@H](NC(=O)c3nc(Cl)c(CC)[nH]3)[C@H](OCC)C2)sc1C(=O)OCC
Yield: 76 %

Procedure:
The same operation as in Example (247a) was performed using cis(±)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-ethoxypiperidin-1-yl)-5-(ethoxycarbonyl)-1,3-thiazole-4-carboxylic acid obtained in Example (50a) (250 mg, 0.50 mmol), 2-ethoxyethylamine (0.11 mL, 1.00 mmol), WSC hydrochloride (288 mg, 1.50 mmol) and 1-hydroxybenzotriazole (68 mg, 0.50 mmol), to obtain 217 mg of the title compound as a white solid (76%).
Reaction SMILES: [CH2:1]([O:3][P:4]([C:9]1[C:10](=[O:24])[NH:11][C:12]2[C:17]([CH:18]=1)=[CH:16][C:15]([S:19](Cl)(=[O:21])=[O:20])=[C:14]([Cl:23])[CH:13]=2)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].Cl.C(OCC)(=O)C.[OH-].[NH4+:33]>>[CH2:1]([O:3][P:4]([C:9]1[C:10](=[O:24])[NH:11][C:12]2[C:17]([CH:18]=1)=[CH:16][C:15]([S:19](=[O:21])(=[O:20])[NH2:33])=[C:14]([Cl:23])[CH:13]=2)(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2]
Reactant: [NH4+]
Reactant: CCOP(=O)(OCC)c1cc2cc(S(=O)(=O)Cl)c(Cl)cc2[nH]c1=O
Agent: Cl
Agent: [OH-]
Solvent: CCOC(C)=O
Product: CCOP(=O)(OCC)c1cc2cc(S(N)(=O)=O)c(Cl)cc2[nH]c1=O
Reaction time: 0.5 h

Procedure:
A suspension of the compound obtained in Step E (1.26 g, 3.0 mmol) in 18 ml of 28 % ammonium hydroxide is stirred. After a few minutes, dissolution is observed. Stirring is continued for 30 minutes and the reaction mixture is acidified with 4N HCl. A few ml of ethyl acetate are added, with stirring, and precipitation is produced. The precipitate is filtered off and dried in vacuo to yield the title product in the form of cream-coloured powder.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH2:9][CH2:8][CH:7]([N:15]([CH3:17])[CH3:16])[CH2:6][C:5]2=1.[F:18][C:19]1[CH:20]=[C:21]([CH:25]=[C:26]([F:28])[CH:27]=1)[C:22](Cl)=[O:23]>>[F:18][C:19]1[CH:20]=[C:21]([CH:25]=[C:26]([F:28])[CH:27]=1)[C:22]([NH:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH2:9][CH2:8][CH:7]([N:15]([CH3:17])[CH3:16])[CH2:6][C:5]2=1)=[O:23]
Reactant: CN(C)C1CCc2[nH]c3ccc(N)cc3c2C1
Reactant: O=C(Cl)c1cc(F)cc(F)c1
Product: CN(C)C1CCc2[nH]c3ccc(NC(=O)c4cc(F)cc(F)c4)cc3c2C1
Yield: 36.5 %

Procedure:
Beginning with 10.4 mg (0.046 mMol) 6-amino-3-(dimethyl)amino-1,2,3,4-tetrahydro-9H-carbazole and 8.6 μL (0.051 mMol) 3,5-difluorobenzoyl chloride, 6.2 mg (36%) of the title compound were recovered as a beige solid.
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH2:12][CH2:13][NH2:14].[F:15][C:16]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:17]=1[CH2:18][C:19]1[O:23][N:22]=[C:21]([C:24](O)=[O:25])[N:20]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH2:12][CH2:13][NH:14][C:24]([C:21]1[N:20]=[C:19]([CH2:18][C:17]2[CH:27]=[C:28]([F:31])[CH:29]=[CH:30][C:16]=2[F:15])[O:23][N:22]=1)=[O:25]
Reactant: NCCc1c[nH]c2ccc(Cl)cc12
Reactant: O=C(O)c1noc(Cc2cc(F)ccc2F)n1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(NCCc1c[nH]c2ccc(Cl)cc12)c1noc(Cc2cc(F)ccc2F)n1
Yield: 12.4 %

Procedure:
This compound was prepared following Method A starting from 2-(5-chloro-1H-indol-3-yl)ethanamine hydrochloride (0.100 g; 0.424 mmol), 5-(2,5-difluorobenzyl)-1,2,4-oxadiazole-3-carboxylic acid (0.102 g; 0.424 mmol), HATU (0.161 g: 0.424 mmol) and N,N-diisopropylethylamine (0.222 mL; 1.27 mmol) in DMF (3 mL). The purification by flash chromatography on silica gel (eluent: 1 to 10% of ethyl acetate in dichloromethane) gave 0.022 g (12%) of N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(2,5-difluorobenzyl)-1,2,4-oxadiazole-3-carboxamide as a solid.
Reaction SMILES: [N:1]([C:4]1[C:12]([CH2:13]/[CH:14]=[C:15](\[CH3:22])/[CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])=[C:11]([O:23][CH3:24])[C:10]([CH3:25])=[C:9]2[C:5]=1[C:6](=[O:26])[O:7][CH2:8]2)=[C:2]=[O:3].[CH3:27][NH:28][CH3:29]>O1CCCC1.O>[CH3:27][N:28]([CH3:29])[C:2](=[O:3])[NH:1][C:4]1[C:12]([CH2:13]/[CH:14]=[C:15](\[CH3:22])/[CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])=[C:11]([O:23][CH3:24])[C:10]([CH3:25])=[C:9]2[C:5]=1[C:6](=[O:26])[O:7][CH2:8]2
Reactant: CNC
Reactant: COC(=O)CC/C(C)=C/Cc1c(N=C=O)c2c(c(C)c1OC)COC2=O
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)CC/C(C)=C/Cc1c(NC(=O)N(C)C)c2c(c(C)c1OC)COC2=O

Procedure:
A solution of 0.65 g (1.8 mmol) of methyl (E)-6-(1,3-dihydro-4-isocyanato-6-methoxy-7-methyl -3-oxoisobenzofuran-5-yl)-4-methyl-4-hexenoate in 10 ml of tetrahydrofuran was treated with 5 ml of a solution of 40% dimethylamine in water. After 1 hour the reaction was partitioned between water and ethyl acetate. The organic phase was washed with water three times, dried over magnesium sulfate, and concentrated under reduced pressure to give 0.4 g of methyl (E)-6-[1,3-dihydro-4-(3,3-dimethylureido)-6-methoxy-7-methyl-3-oxoisobenzofuran-5-yl]-4-methyl-4-hexenoate, mp 116°-118° C.
Reaction SMILES: P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:2].[C:15]([C:19]1[CH:47]=[CH:46][C:22]([CH2:23][N:24]2[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[N:26]([CH2:33][C:34]3[CH:39]=[CH:38][C:37]([NH:40][S:41]([CH3:44])(=[O:43])=[O:42])=[CH:36][CH:35]=3)[C:25]2=O)=[CH:21][CH:20]=1)([CH3:18])([CH3:17])[CH3:16].[OH-].[Na+].[Na+].[Cl-]>C1(C)C=CC(C)=CC=1.O>[C:15]([C:19]1[CH:47]=[CH:46][C:22]([CH2:23][N:24]2[C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=3[N:26]([CH2:33][C:34]3[CH:39]=[CH:38][C:37]([NH:40][S:41]([CH3:44])(=[O:43])=[O:42])=[CH:36][CH:35]=3)[C:25]2=[S:2])=[CH:21][CH:20]=1)([CH3:18])([CH3:17])[CH3:16]
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Reactant: CC(C)(C)c1ccc(Cn2c(=O)n(Cc3ccc(NS(C)(=O)=O)cc3)c3ccccc32)cc1
Agent: [Cl-]
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccc(C)cc1
Solvent: O
Product: CC(C)(C)c1ccc(Cn2c(=S)n(Cc3ccc(NS(C)(=O)=O)cc3)c3ccccc32)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 40.5 %

Procedure:
Phosphorus pentasulfide (300 mg, 0.67 mmol) was added to a suspension of N-{4-[3-(4-tert-butylbenzyl)-2-oxo-2,3-dihydrobenzimidazol-1-ylmethyl]phenyl}methanesulfonamide (6) (235 mg, 0.51 mmol) in para-xylene (20 mL) under a blanket of argon. The reaction mixture was heated to the boil over a period of 5 h. Following cooling, there was added to the reaction mixture water (1 mL) followed by 2N NaOH solution in water (10 mL), and the mixture was stirred at RT for 30 min. To the reaction mixture there was added aqueous NaCl solution, and the resulting mixture was extracted with ethyl acetate (4×20 mL). The combined organic phases were dried over Na2SO4 and the solvent removed in vacuo. After purifying the residue by means of column chromatography (SiO2; cyclohexane/EtOAc 7:3), the desired product N-{4-[3-(4-tert-butylbenzyl)-2-thioxo-2,3-dihydrobenzoimidazol-1-ylmethyl]phenyl}methanesulfonamide (2) (99 mg, 40% of theory, mp: 176-178° C.) was obtained.
Reaction SMILES: [OH:1][CH:2]([CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])/[CH:3]=[CH:4]/[CH:5]1[CH2:9][CH2:8][C:7](=[O:10])[CH:6]1[CH2:11]/[CH:12]=[CH:13]\[CH2:14][CH2:15][CH2:16][C:17]([OH:19])=[O:18].[BH4-].[Na+].C(O)(=O)C>CO>[OH:1][CH:2]([CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])/[CH:3]=[CH:4]/[CH:5]1[CH2:9][CH2:8][CH:7]([OH:10])[CH:6]1[CH2:11]/[CH:12]=[CH:13]\[CH2:14][CH2:15][CH2:16][C:17]([OH:19])=[O:18]
Reactant: CCCCCC(O)/C=C/C1CCC(=O)C1C/C=C\CCCC(=O)O
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: CCCCCC(O)/C=C/C1CCC(O)C1C/C=C\CCCC(=O)O

Procedure:
50 mg of 7-[2-(3-hydroxy-3-pentyl-trans-1-propenyl)-5-oxo-cyclo-pentyl]-cis-5-heptenoic acid were dissolved in 20 ml of methanol and in the course of 1.5 hours three 50 mg portions of NaBH4 were added. The reaction solution was adjusted to pH 7 with glacial acetic acid, the solvent was distilled off under reduced pressure, the residue was acidified in 1 ml of H2O with 2 N hydrochloric acid to pH 1 and extracted three times with 150 ml portions of ether. The combined ether extracts were washed with water, dried and condensed.
Reaction SMILES: Cl.O[CH:3]1[O:11][C@H:10]([CH2:12][OH:13])[C@@H:8]([OH:9])[C@H:6]([OH:7])[C@H:4]1[NH2:5].[S-:14][C:15]#[N:16].[NH4+]>O>[SH:14][C:15]1[NH:16][CH:3]=[C:4]([C@@H:6]([OH:7])[C@H:8]([OH:9])[C@H:10]([OH:11])[CH2:12][OH:13])[N:5]=1
Reactant: N#C[S-]
Reactant: N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O
Agent: Cl
Agent: [NH4+]
Solvent: O
Product: OC[C@@H](O)[C@@H](O)[C@H](O)c1c[nH]c(S)n1
Temperature: 84.5 °C
Reaction time: 8 h
Yield: 49.6 %

Procedure:
To glucosamine hydrochloride (200 g, 0.928 mol) were added water (300 mL) and ammonium thiocyanate (212 g, 2.78 mol, 3.0 equivalents) at 25° C., and the mixture was stirred at 80 to 89° C. for 8 hr. The reaction mixture was allowed to cool to 60° C., water (300 mL) and seed crystals were added thereto, and the mixture was stirred at 25 to 40° C. for 15 hr. The crystals were collected by filtration, washed twice with water (100 mL), and vacuum-dried (50° C.) to a constant amount to give (1R,2S,3R)-1-(2-sulfanyl-1H-imidazol-4-yl)butane-1,2,3,4-tetraol (101.4 g). yield 50%.
Reaction SMILES: [CH:1]1([CH2:6][C:7]([NH:9][C:10]2[CH:18]=[C:17]3[C:13]([C:14]([OH:32])=[N:15][N:16]3[CH2:19][C:20]3[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][C:21]=3[O:30][CH3:31])=[CH:12][CH:11]=2)=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:33](Br)[CH:34]=[CH2:35].[H-].[Na+].C(N1C(=O)C2C(=CC(NC(=O)CC3CCCC3)=CC=2)N1CC1C=CC(C(OC)=O)=CC=1OC)C=C>CN(C)C=O>[CH2:35]([O:32][C:14]1[C:13]2[C:17](=[CH:18][C:10]([NH:9][C:7](=[O:8])[CH2:6][CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)=[CH:11][CH:12]=2)[N:16]([CH2:19][C:20]2[CH:29]=[CH:28][C:23]([C:24]([O:26][CH3:27])=[O:25])=[CH:22][C:21]=2[O:30][CH3:31])[N:15]=1)[CH:34]=[CH2:33]
Reactant: C=CCBr
Reactant: COC(=O)c1ccc(Cn2nc(O)c3ccc(NC(=O)CC4CCCC4)cc32)c(OC)c1
Agent: C=CCn1c(=O)c2ccc(NC(=O)CC3CCCC3)cc2n1Cc1ccc(C(=O)OC)cc1OC
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C=CCOc1nn(Cc2ccc(C(=O)OC)cc2OC)c2cc(NC(=O)CC3CCCC3)ccc12

Procedure:
The starting ester methyl 4-[2-allyl-6-(2-cyclopentylacetamido)-3-oxo-2H,3H-indazol-1-ylmethyl]-3-methoxybenzoate was itself prepared as follows. Using a similar procedure to that described in Example 42, except starting from methyl 4-[6-(2-cyclopentylacetamido)-3-hydroxyindazol-1-ylmethyl]-3-methoxybenzoate (that is, reaction of this compound with allyl bromide in N,N-dimethylformamide in the presence of sodium hydride), a mixture of methyl 4-[2-allyl-6-(2-cyclopentylacetamido)-3-oxo-2H,3H-indazol-1-ylmethyl]-3-methoxybenzoate, and methyl 4-[3-allyloxy-6-(2-cyclopentylacetamido)indazol-1-ylmethyl]-3-methoxybenzoate was obtained. The mixture of compounds was heated neat at 200° C. for 18 hours, and the product isolated by flash chromatography on silica gel (60 g.), eluting with 1:30:70 v/v/v acetic acid:ethyl acetate:dichloromethane, to give methyl 4-[2-allyl-6-(2-cyclopentylacetamido)-3-oxo-2H,3H-indazol-1-ylmethyl]-3-methoxybenzoate in 81% yield, as an oil with satisfactory NMR spectral data.
Reaction SMILES: [C:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5][CH:4]=1)#[N:2].[CH2:12]1N2CCN(CC2)C1>CCOC(C)=O.O>[C:1]([C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([CH3:12])[CH:4]=1)#[N:2]
Reactant: C1CN2CCN1CC2
Reactant: N#Cc1c[nH]c2ccccc12
Solvent: CCOC(C)=O
Solvent: O
Product: Cn1cc(C#N)c2ccccc21
Temperature: 25 °C
Yield: 987.8 %

Procedure:
To a solution of 3-cyanoindole (1.0 g, 7.03 mmol) in DMC (10 mL), DABCO (0.079 g, 0.70 mmol) is added and the resulting solution is heated to reflux for 8 h. The reaction is cooled to RT, and diluted with EtOAc (40 mL) and H2O (40 mL). The organic layer is separated and washed in sequence with H2O (50 mL), 10% aqueous citric acid (2×40 mL) and H2O (4×40 mL). The organic layer is dried over anhydrous Na2SO4, filtered and concentrated under vacuum to give 3-cyano-1-methylindole (about 1.08 g, 98%) as an oil: 1H NMR (CDCl3) δ7.74 (d, 1H), 7.53 (s, 1H), 7.40-7.28 (m, 3H), 3.83 (s, 3H); 13C NMR (CDCl3) 136.0, 135.6, 127.8, 123.8, 122.1, 119.8, 116.0, 110.4, 85.4, 33.6; MS m/z 156 [M+1]+.
Reaction SMILES: C([O:4][CH:5]1[CH:9]([N:10]2[C:14]3[CH:15]=[C:16]([Cl:20])[C:17]([Cl:19])=[CH:18][C:13]=3[N:12]=[C:11]2Br)[CH2:8][CH:7]([CH3:22])[CH:6]1[O:23]C(=O)C)(=O)C.[CH:27]1([NH2:30])[CH2:29][CH2:28]1.[OH-].[Na+]>COC(O)C>[Cl:19][C:17]1[C:16]([Cl:20])=[CH:15][C:14]2[N:10]([CH:9]3[CH:5]([OH:4])[CH:6]([OH:23])[CH:7]([CH3:22])[CH2:8]3)[C:11]([NH:30][CH:27]3[CH2:29][CH2:28]3)=[N:12][C:13]=2[CH:18]=1
Reactant: NC1CC1
Reactant: CC(=O)OC1C(C)CC(n2c(Br)nc3cc(Cl)c(Cl)cc32)C1OC(C)=O
Agent: COC(C)O
Agent: [Na+]
Agent: [OH-]
Product: CC1CC(n2c(NC3CC3)nc3cc(Cl)c(Cl)cc32)C(O)C1O
Yield: 64 %

Procedure:
(±)-(1R*, 2S*, 3R*, 5S*)-5-(2-Bromo-5,6-dichloro-1H-benzimidazol-1-yl)-3-methyl-1,2-cyclopentanediyl diacetate (Part D, 350 mg, 0.75 mmole) and cyclopropylamine (Aldrich, 0.53 mL) were refluxed in methoxyethanol (5 mL) for 5 hours. 1N sodium hydroxide (0.75 mL) was added to the cooled reaction mixture and volatiles were evaporated in vacuo. The residue was chromatographed on silica gel. Product was eluted with 5% methanol-chloroform. Recrystallization from methanol-ethyl acetate gave (±)-(1R*, 2S*, 3R*, 5S*)-5-[5,6-dichloro-2-(cyclopropylamino)-1H-benzimidazol-1-yl]-3-methyl-1,2-cyclopentanediol as white crystals (170 mg, 64%); m.p. 231°-233° C.; 1H-NMR(DMSO-d6)δ: 7.48 and 7.39 (both s, 1 each, 2 benzimidazole CH), 7.10 (m, 1, NH), 4.83 (d, J=5.9 Hz, 1, OH), 4.74 (d, J=5.1 Hz, 1, OH), 4.5-4.3 (m, 2, NCH and OCH), 3.7-3.6 (m, 1, OCH), 2.85-2.7 (m, 1, CHNH), 2.1-1.8 (m, 2, CH2 and CH), 1.7-1.5 (m, 1, CH), 1.16 (d, J=5.4 Hz, 3, CHCH3), 0.8-0.5 (m, 4, 2 CH2 of cyclopropyl); mass spectrum (CI): 356 (M+1).
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[C:8]([CH:9]=O)[C:7]([OH:12])=[CH:6][CH:5]=1)([O-:3])=[O:2].[NH2:13][C:14]([CH2:20][C:21]#[N:22])=[C:15]([C:18]#[N:19])[C:16]#[N:17].C(O)(=O)C.C([SiH](CC)CC)C>C(O)C>[NH2:17][C:16]1[N:22]=[C:21]2[O:12][C:7]3[C:8]([CH2:9][C:20]2=[C:14]([NH2:13])[C:15]=1[C:18]#[N:19])=[CH:11][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=3
Reactant: N#CCC(N)=C(C#N)C#N
Reactant: O=Cc1cc([N+](=O)[O-])ccc1O
Agent: CC[SiH](CC)CC
Solvent: CC(=O)O
Solvent: CCO
Product: N#Cc1c(N)nc2c(c1N)Cc1cc([N+](=O)[O-])ccc1O2
Temperature: 66 °C
Yield: 60.1 %

Procedure:
5-nitrosalicylaldehyde (132 mmol, 22.00 g), 2-amino-1-propene-1,1,3-tricarbonitrile (132 mmol, 17.39 g), acetic acid (31 mL), and ethanol (500 mL) were combined and heated to reflux overnight. The resulting slurry was concentrated in vacuo and then dissolved in trifluoroacetic acid (350 mL) at 0° C. Triethylsilane (1.40 mol, 162 g, 225 mL) was added. The mixture was heated overnight at 66° C. The mixture was cooled and concentrated in vacuo. Triturating with methanol gave 2,4-diamino-7-nitro-5H-chromeno[2,3-b]pyridine-3-carbonitrile as a yellow solid (22.48 g, 60% yield). 1H NMR (300 MHz, DMSO-d6): δ 8.13 (d, J=9.0 Hz, 1H), 8.00 (s, 1H), 7.25 (d, J=9.0 Hz, 1H), 6.70 (br s, 2H), 6.50 (bs, 2H), 3.82 (s, 2H); m/z 284 (M+H); Anal. Calcd for C13H9N5O3-0.5H2O: C, 53.43; H, 3.45; N, 23.96, found: C, 53.41; H, 3.17; N, 23.71.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:12]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:14]=1)[C:6](N(OC)C)=[O:7].[CH3:19][Mg]Br>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:6](=[O:7])[CH3:19])[CH:12]=[C:13]([C:15]([F:16])([F:17])[F:18])[CH:14]=1
Reactant: COc1cc(C(=O)N(C)OC)cc(C(F)(F)F)c1
Reactant: C[Mg]Br
Solvent: C1CCOC1
Product: COc1cc(C(C)=O)cc(C(F)(F)F)c1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
3,N-Dimethoxy-N-methyl-5-trifluoromethylbenzamide (O3.014, 460 mg) was initially charged in THF (15 ml) under at RT Ar dissolved. Thereafter, the mixture was cooled to 0° C., and methylmagnesium bromide (1.5 ml; 3 M in diethyl ether) was added dropwise. Subsequently, the ice bath was removed and the mixture was stirred at RT for 2 h. Then the mixture was admixed with 1 N hydrochloric acid while cooling with ice, diluted with water and extracted three times with EA. The combined EA phases were dried over sodium sulfate, filtered and concentrated. 349 mg of the title compound were isolated.
Reaction SMILES: [BH4-].[Na+].[Cl:3][C:4]1[CH:26]=[CH:25][C:7]2[C:8]3[C:9](=[C:20]([CH:23]=[O:24])[NH:21][CH:22]=3)[CH2:10][N:11]=[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[C:6]=2[CH:5]=1.O.[CH3:28]O>>[Cl:3][C:4]1[CH:26]=[CH:25][C:7]2[C:8]3[C:9](=[C:20]([CH2:23][OH:24])[NH:21][C:22]=3[CH3:28])[CH2:10][N:11]=[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[C:6]=2[CH:5]=1
Reactant: O=Cc1[nH]cc2c1CN=C(c1ccccc1Cl)c1cc(Cl)ccc1-2
Reactant: CO
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Product: Cc1[nH]c(CO)c2c1-c1ccc(Cl)cc1C(c1ccccc1Cl)=NC2
Reaction time: 0.5 h

Procedure:
In one portion 0.2 g (5.2 mmol) of sodium borohydride was added to 0.9 g of 8-chloro-6-(2-chlorophenyl)-2H,4H-pyrrolo[3,4-d][2]benzazepine-3-carboxaldehyde in 20 ml of methanol which was cooled to 0°. After stirring at 0° for 30 min, water was added and the resulting precipitate was collected by filtration to give a tan amorphous solid (mp 170°-180° dec.). All attempts to purify this product led to the introduction of impurities by decomposition.
Reaction SMILES: [CH3:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:11][N:12]([CH:14](OC)OC)[CH3:13]>CN(C=O)C>[CH3:11][N:12]([CH3:14])/[CH:13]=[CH:1]/[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: COC(OC)N(C)C
Reactant: Cc1ncccc1[N+](=O)[O-]
Solvent: CN(C)C=O
Product: CN(C)/C=C/c1ncccc1[N+](=O)[O-]
Temperature: 90 °C
Reaction time: 0.25 h
Yield: 73 %

Procedure:
A modified procedure of Cash et al. (Org. Biomol. Chem. 2005, 3. 3701-3706) was used. 2-Methyl-3-nitropyridine (0.7 g, 5.1 mmol) was dissolved in 15 ml dry DMF and stirred under nitrogen. Dimethylformamiddimethylacetal (DMF-DMA) (1.35 ml, 1.22 g, 10.2 mmol) was added dropwise. The reaction was heated to 90° C. for 4 h. After approximately 15 min a deep redish color appeared. After evaporating the solvent (E)-N,N-Dimethyl-2-(3-nitropyridin-2-yl)ethenamine is obtained as a red oil (0.16 g, 0.8 mmol, 73%) which can be used without further purification. 1H NMR (300 MHz, CDCl3) 8.40 (pdd; 3J=1.7 Hz; 3J=4.4 Hz; 1H; H-6); 8.16 (pdd; 3J=1.7 Hz; 3J=8.3 Hz; 1H; H-4); 8.04 (d; 3JAX=12.5 Hz; 1H; H-8); 6.76 (pdd; 3J=4.4 Hz; 3J=8.3 Hz; 1H; H-5); 6.15 (d; 3JAX=12.5 Hz; 1H; H-7); 3.01 (s; 6H; CH3).