Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1]1[C:5]([C:6](=[O:8])[CH3:7])=[CH:4][C:3]2[CH2:9][CH2:10][C:11]3[C:16]([C:2]1=2)=[CH:15][CH:14]=[C:13]([C:17](=[O:19])[CH3:18])[CH:12]=3.C(C1C(=O)C(Cl)=C(Cl)C(=O)C=1C#N)#N>C1(C)C=CC=CC=1>[S:1]1[C:5]([C:6](=[O:8])[CH3:7])=[CH:4][C:3]2[CH:9]=[CH:10][C:11]3[C:16]([C:2]1=2)=[CH:15][CH:14]=[C:13]([C:17](=[O:19])[CH3:18])[CH:12]=3
Reactant: CC(=O)c1ccc2c(c1)CCc1cc(C(C)=O)sc1-2
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: Cc1ccccc1
Product: CC(=O)c1ccc2c(ccc3cc(C(C)=O)sc32)c1
Temperature: 110 °C
Reaction time: 60 h
Yield: 45.3 %

Procedure:
To a stirred solution of 1,1′-(4,5-dihydronaphtho[1,2-b]thiophene-2,7-diyl))diethanone (5c) (1 g, 3.7 mmol) in 30 ml of toluene, DDQ (0.84 g, 3.7 mmol) was added and the mixture was stirred at 110° C. for 60 hr. The reaction mixture was concentrated under reduced pressure, 100 ml water was added and the organics were extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure to obtain the crude compound which was purified by column chromatography to obtain 1,1′-(naphtho[1,2-b]thiophene-2,7-diyl)diethanone as a brown solid (10a) (0.45 g, 55%).
Reaction SMILES: [N+:1]([C:4]1[N:9]=[CH:8][C:7]([NH:10][S:11]([CH3:14])(=[O:13])=[O:12])=[CH:6][CH:5]=1)([O-])=O.[Cl-].[NH4+]>CO.O.[Zn]>[NH2:1][C:4]1[N:9]=[CH:8][C:7]([NH:10][S:11]([CH3:14])(=[O:13])=[O:12])=[CH:6][CH:5]=1
Reactant: CS(=O)(=O)Nc1ccc([N+](=O)[O-])nc1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: O
Solvent: CO
Product: CS(=O)(=O)Nc1ccc(N)nc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 76.5 %

Procedure:
A solution of N-(6-nitro-pyridin-3-yl)-methanesulfonamide (298 mg, 1.37 mmol) in methanol (8.3 mL) was treated with a solution of ammonium chloride (154 mg, 2.88 mmol) in water (1 mL). This solution was stirred at 25° C. for 5 min. At this time, zinc dust (879 mg, 13.44 mmol) was added to the reaction. The resulting reaction mixture was then heated under reflux for 3 h. At this time, the reaction was cooled to 25° C. and then was filtered through a pad of celite (9/1 methylene chloride/methanol wash). The filtrate was concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 9/1 methylene chloride/methanol) afforded N-(6-amino-pyridin-3-yl)-methanesulfonamide (196.3 mg, 76.4%) as a reddish-brown oil: EI-HRMS m/e calcd for C6H9N3O2S (M+) 184.0415, found 184.0415.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([F:12])[CH:3]=1.[OH:13][CH:14]1[CH2:18][CH2:17][NH:16][CH2:15]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:12][C:4]1[CH:3]=[C:2]([N:16]2[CH2:17][CH2:18][CH:14]([OH:13])[CH2:15]2)[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=1
Reactant: Fc1cc(Br)cc(C(F)(F)F)c1
Reactant: OC1CCNC1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Product: OC1CCN(c2cc(F)cc(C(F)(F)F)c2)C1
Temperature: 25 °C
Yield: 104 %

Procedure:
A solution of 1-bromo-3-fluoro-5-(trifluoromethyl)benzene (10.0 g), 3-hydroxypyrrolidine (3.58 g), palladium(II) acetate (461 mg), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (2.56 g) and cesium carbonate (26.7 g) in toluene (222 ml) was stirred under an argon gas atmosphere at 90° C. for 16 hr. After cooling to room temperature, the reaction mixture was filtered through celite, and the celite was washed with ethyl acetate. The filtrate and washing were combined and the solution was washed with water and saturated brine. This was dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate 98:2-20:80) to give the title compound (10.65 g, yield quant.) as a brown oil.
Reaction SMILES: Br[CH2:2][CH2:3][N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([CH2:13][C:14]2[C:15]3[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][C:16]=3[S:17][CH:18]=2)[C:5]1=[O:24].[NH4+:25].[OH-]>C1COCC1>[NH2:25][CH2:2][CH2:3][N:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([CH2:13][C:14]2[C:15]3[C:22]([CH3:23])=[CH:21][CH:20]=[CH:19][C:16]=3[S:17][CH:18]=2)[C:5]1=[O:24]
Reactant: Cc1cccc2scc(Cn3c(=O)n(CCBr)c4ccccc43)c12
Reactant: [NH4+]
Agent: [OH-]
Solvent: C1CCOC1
Product: Cc1cccc2scc(Cn3c(=O)n(CCN)c4ccccc43)c12
Temperature: 65 °C
Reaction time: 16 h
Yield: 61 %

Procedure:
1-(2-Bromo-ethyl)-3-(4-methyl-benzo[b]thiophen-3-ylmethyl)-1,3-dihydro-benzimidazol-2-one (55 mg, 0.14 mmol) is dissolved in THF (1.5 mL) and NH4OH (1.5 mL, 27% aqueous) is added into it at room temperature. The mixture is then stirred for 16 hr at 65° C. and another one week at room temperature. Then the solvents are removed under vacuum and the residue is washed with THF. The solid formed is filtered and rinsed with more THF to give 28 mg (61%) of 1-(2-Amino-ethyl)-3-(4-methyl-benzo[b]thiophen-3-ylmethyl)-1,3-dihydro-benzimidazol-2-one.
Reaction SMILES: [C:1](=[O:8])([O:3][CH2:4][CH2:5][CH2:6][CH3:7])[NH2:2].[C:9](Cl)(Cl)=[O:10]>CCCCCCCCCCCCCCCCCCCNC=O.ClC1C=CC=CC=1>[CH2:4]([O:3][C:1]([N:2]=[C:9]=[O:10])=[O:8])[CH2:5][CH2:6][CH3:7]
Reactant: CCCCOC(N)=O
Reactant: O=C(Cl)Cl
Agent: CCCCCCCCCCCCCCCCCCCNC=O
Solvent: Clc1ccccc1
Product: CCCCOC(=O)N=C=O
Reaction time: 6 h
Yield: 45 %

Procedure:
58.5 g of n-butyl carbamate were initially introduced as a melt and 86 g of phosgene were passed into this melt at 80° C. within 6 hours. 3.1 g (=2 mol %) of methylstearylformamide and 125 g of chlorobenzene were then added. A further 113 g of phosgene were then passed into the mixture at 130° C. within 6 hours and excess phosgene was subsequently blown out using nitrogen. The distillation of the reaction mixture produced 32.2 g (=45% of theory) of butyloxycarbonyl isocyanate having a boiling point from 52° to 54° C. at 24 mbar.
Reaction SMILES: Br[C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[C:12]1([CH3:22])[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1OB(O)O>>[C:12]1([CH3:22])[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1
Reactant: O=C1Cc2ccc(Br)cc2N1
Reactant: Cc1ccccc1OB(O)O
Product: Cc1ccccc1-c1ccc2c(c1)NC(=O)C2

Procedure:
Prepared from 6-bromo-2-indolinone and 2-tolylboric acid
Reaction SMILES: [CH3:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:6]=1[F:12])=[O:4].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[C:23]([C:25]1[CH:32]=[CH:31][C:28]([CH2:29]Br)=[CH:27][CH:26]=1)#[N:24].[Cl-].[NH4+]>O1CCCC1.O>[F:12][C:6]1[CH:7]=[C:8]([F:11])[CH:9]=[CH:10][C:5]=1[C:3](=[O:4])[CH:2]([CH3:1])[CH2:29][C:28]1[CH:31]=[CH:32][C:25]([C:23]#[N:24])=[CH:26][CH:27]=1
Reactant: N#Cc1ccc(CBr)cc1
Reactant: CCC(=O)c1ccc(F)cc1F
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Cl-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: CC(Cc1ccc(C#N)cc1)C(=O)c1ccc(F)cc1F
Reaction time: 1 h
Yield: 41 %

Procedure:
A 19 g portion of 2,4-difluoropropiophenone was dissolved in 150 ml of tetrahydrofuran. With cooling in a dry ice-acetone bath and spending 20 minutes or more, to this was added dropwise 112 ml of 1N tetrahydrofuran solution of lithium hexamethyl disilazide. After 1 hour of stirring at the same temperature, to this was further added dropwise 50 ml of tetrahydrofuran solution containing 14 g of 4-cyanobenzyl bromide spending 20 minutes or more, followed by overnight stirring at room temperature. The reaction solution was mixed with saturated ammonium chloride aqueous solution, poured into water and then extracted with ethyl acetate. The thus obtained organic layer was washed with water and dried on anhydrous magnesium sulfate. After removing the solvent by evaporation under a reduced pressure, the resulting residue was purified by a silica gel column chromatography (ethyl acetate:n-hexane=1:9) to obtain 13 g of 2',4'-difluoro-2-methyl-3-(4-cyanophenyl)-propiophenone with a yield of 41%.
Reaction SMILES: [O:1]=[C:2]1[NH:6][C:5]2[CH:7]=[CH:8][C:9]([C:11]#N)=[CH:10][C:4]=2[O:3]1.[OH2:13]>C(O)=O.[Al].[Ni]>[O:1]=[C:2]1[NH:6][C:5]2[CH:7]=[CH:8][C:9]([CH:11]=[O:13])=[CH:10][C:4]=2[O:3]1
Reactant: N#Cc1ccc2[nH]c(=O)oc2c1
Reactant: O
Agent: [Ni]
Agent: [Al]
Solvent: O=CO
Product: O=Cc1ccc2[nH]c(=O)oc2c1
Yield: 97 %

Procedure:
A mixture of 2-oxo-2,3-dihydro-1,3-benzoxazole-6-carbonitrile (Intermediate 6, 220 mg; 1.37 mmol) and aluminium/nickel 1:1 alloy (223.6 mg; 2.61 mmol) in 2.25 ml of formic acid and 0.75 ml of water is stirred at 90° C. for 24 hr. The solid is filtered and washed with ethanol. The filtrate is concentrated in vacuo and dried overnight at 45° C. in a vacuum dessicator. The solid obtained (219 mg; 97% yield) is pure enough as to prosecute with the synthesis.
Reaction SMILES: C([Mg]Cl)(C)C.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]([CH3:15])[CH3:14])=[C:9](I)[CH:8]=1.C[O:18][B:19](OC)[O:20]C.Cl>C1COCC1>[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]([CH3:15])[CH3:14])=[C:9]([B:19]([OH:20])[OH:18])[CH:8]=1
Reactant: CC(C)c1ccc(Cl)cc1I
Reactant: COB(OC)OC
Agent: CC(C)[Mg]Cl
Agent: Cl
Solvent: C1CCOC1
Product: CC(C)c1ccc(Cl)cc1B(O)O
Reaction time: 0.5 h
Yield: 79 %

Procedure:
i-Propylmagnesium chloride (2 M in THF, 3.34 mL, 6.7 mmol) was added drop wise to a solution of 4-chloro-2-iodo-1-(propan-2-yl)benzene (1.7 g, 6.7 mmol) in dry THF (15 mL) at −30° C. and the reaction mixture was stirred at the same temperature for 30 min, under argon. After this time, trimethylborate (1.35 mL, 12.1 mmol) was added drop wise and the reaction mixture was stirred at the same temperature for 1.5 h. HCl (1 M, 6 mL) was added and the reaction mixture extracted with EtOAc (3×20 mL). The combined organic layers were dried over sodium sulfate and, after removal of the solvent, a solid was obtained, which was triturated with hexane to obtain the title compound as a white solid (1.05 g, 87%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[C:5]#[N:6].Cl.[NH2:11][OH:12].C(=O)([O-])[O-].[K+].[K+]>C(O)C>[NH2:1][C:2]1[CH:3]=[C:4]([C:5](=[NH:6])[NH:11][OH:12])[CH:7]=[CH:8][CH:9]=1
Reactant: N#Cc1cccc(N)c1
Reactant: NO
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: N=C(NO)c1cccc(N)c1
Temperature: 25 °C
Yield: 103.5 %

Procedure:
To a stirred solution of 3-aminobenzonitrile (4.0 g) (available from Aldrich) in ethanol (100 ml) was added hydroxylamine hydrochloride (4.7 g) and potassium carbonate (14.0 g) and the mixture heated under reflux for 22 h. After cooling to room temperature the mixture was filtered through ‘hyflo’ filter aid, the residue washed with ethanol, and the filtrates concentrated in vacuo to give the title compound as a viscous oil (5.3 g).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][CH:10]=[C:11]([CH:13]([O:16][CH3:17])[CH2:14][NH2:15])[N:12]=2)=[CH:4][CH:3]=1.[F:18][C:19]([F:35])([F:34])[C:20]1[O:24][N:23]=[C:22]([C:25]2[CH:26]=[C:27]([CH:31]=[CH:32][CH:33]=2)[C:28](O)=[O:29])[N:21]=1>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][CH:10]=[C:11]([CH:13]([O:16][CH3:17])[CH2:14][NH:15][C:28](=[O:29])[C:27]3[CH:31]=[CH:32][CH:33]=[C:25]([C:22]4[N:21]=[C:20]([C:19]([F:35])([F:34])[F:18])[O:24][N:23]=4)[CH:26]=3)[N:12]=2)=[CH:6][CH:7]=1
Reactant: COC(CN)c1coc(-c2ccc(F)cc2)n1
Reactant: O=C(O)c1cccc(-c2noc(C(F)(F)F)n2)c1
Product: COC(CNC(=O)c1cccc(-c2noc(C(F)(F)F)n2)c1)c1coc(-c2ccc(F)cc2)n1
Yield: 22 %

Procedure:
This compound was synthesized from 2-(2-(4-fluorophenyl)oxazol-4-yl)-2-methoxyethanamine and 3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid as described in example 8 step 6 (44 mg, yield 22%) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 8.56-8.55 (t, J=1.6 Hz, 1H), 8.29-8.26 (dt, J=7.9 Hz, 1.3 Hz, 1H), 8.11-8.06 (m, 3H), 7.73 (s, 1H), 7.67-7.63 (t, J=7.7 Hz, 1H), 7.22-7.19 (m, 1H), 7.17-7.13 (t, J=8.7 Hz, 2H), 4.54-4.51 (dd, J=5.9 Hz, 5.1 Hz, 1H), 4.12-4.06 (ddd, J=13.9 Hz, 6.5 Hz, 4.9 Hz, 1H), 3.87-3.81 (ddd, J=13.9 Hz, 6.1 Hz, 4.8 Hz, 1H), 3.45 (s, 3H). MS (ESI) m/z: Calculated for C22H16F4N4O4: 476.11. found: 475.6 (M)−.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)=[CH:3][CH:2]=1.[Br:13][C:14]1[CH:22]=[CH:21][C:17]([C:18](Cl)=[O:19])=[CH:16][CH:15]=1>ClCCl.C(N(CC)CC)C>[N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:8][CH2:9][N:10]([C:18](=[O:19])[C:17]3[CH:21]=[CH:22][C:14]([Br:13])=[CH:15][CH:16]=3)[CH2:11][CH2:12]2)=[CH:3][CH:2]=1
Reactant: O=C(Cl)c1ccc(Br)cc1
Reactant: c1cc(N2CCNCC2)ccn1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(c1ccc(Br)cc1)N1CCN(c2ccncc2)CC1
Reaction time: 2 h
Yield: 59.7 %

Procedure:
A solution of 1-(4-pyridyl)piperazine (0.49 g) in dry dichloromethane (20 ml) and triethylamine (0.7 ml) was treated slowly with a solution of 4-bromobenzoyl chloride (0.7 g) in dry dichloromethane (10 ml). The reaction mixture was then stirred under argon for 2 hours. The dichloromethane solvent was removed by evaporation and the residue dissolved in ethyl acetate. The organic extracts were then washed with aqueous sodium hydrogen carbonate solution, water, brine, dried (Na2SO4) and evaporated to yield a colourless oil. The residual oil was then triturated with diethyl ether and recrystallised from ethyl acetate/isohexane to give 1-(4-pyridyl)-4-(4-bromobenzoyl)piperazine (0.62 g) as a solid, m.p. 128-129° C.; microanalysis, found: C, 55.7; H, 4.7; N, 12.0%; C16H16N3OBr requires: C, 55.5; H, 4.7; N, 12.1%; NMR: (CDCl3) 3.36(s,4H), 3.73(s,4H), 6.67(dd,2H), 7.33(dd,2H), 7.58(dd,2H), 8.34(dd,2H); MS: m/z 346 (MH)+.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][NH:9][OH:10].N1C=CC=CC=1.C[Si](C)(C)Cl.[Cl:22][CH2:23][C:24]([CH3:29])([CH3:28])[C:25](Cl)=[O:26]>C(Cl)Cl.CCCCCC>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][N:9]([OH:10])[C:25](=[O:26])[C:24]([CH3:29])([CH3:28])[CH2:23][Cl:22]
Reactant: CC(C)(CCl)C(=O)Cl
Reactant: ONCc1ccccc1Br
Agent: C[Si](C)(C)Cl
Solvent: CCCCCC
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(C)(CCl)C(=O)N(O)Cc1ccccc1Br
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 40.4 %

Procedure:
Under an argon atmosphere a stirred solution of 8.8 grams (0.044 mole) of N-(2-bromophenylmethyl)hydroxylamine and 12.0 grams (0.152 mole) of pyridine in 200 ml of methylene chloride was cooled to -10°. The reaction vessel was fitted with a septum and 5.2 grams (0.048 mole) of trimethylchlorosilane was added in small portions from a hypodermic syringe. Upon completion of addition the reaction mixture was stirred at -10° for 30 minutes, then allowed to warm to 0°. At this temperature a solution of 6.7 grams (0.044 mole) of 3-chloro-2,2-dimethylpropionyl chloride (prepared in the manner of Example 1, Step B) in 5 ml of methylene chloride was added dropwise over a 20-minute period. Upon completion of addition the reaction mixture was allowed to warm to ambient temperature where it was stirred for 18 hours. The reaction mixture was poured into a separatory funnel and diluted with 50 ml of methylene chloride. The mixture was washed with 50 ml of water, 50 ml of an aqueous solution saturated with sodium chloride, two portions of 100 ml each of a solution consisting of 1:1--aqueous saturated sodium chloride solution:aqueous 10% hydrochloric acid solution, and finally 50 ml of an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to give a semi-solid residue. The semi-solid was slurried in 15 ml of hexane. The insoluble material was collected by filtration and recrystallized twice from hexane/ethyl acetate to give 5.7 grams of N-(2-bromophenyl)methyl-3-chloro-N-hydroxy-2,2-dimethylpropanamide; mp 119°-121°.
Reaction SMILES: [O:1]=[C:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH:12]=3)[CH:8]=2)[NH:3]1>C1COCC1.CO.[Pd]>[O:1]=[C:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)[CH:8]=2)[NH:3]1
Reactant: CC(C)(C)OC(=O)N1CC=C(c2ccc3c(c2)CC(=O)N3)CC1
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(c2ccc3c(c2)CC(=O)N3)CC1
Temperature: 25 °C
Reaction time: 7 h
Yield: 92.2 %

Procedure:
To a solution of tert-butyl 4-(2-oxoindolin-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (912 mg, 2.90 mmol) in THF (10 ml) and MeOH (10 ml) was added 10% Pd/C (453 mg) and stirred at room temperature under H2 (1 atom) atmosphere for 7 h. The reaction mixture was filtered through a Celite pad and concentrated. The residue was purified by column chromatography (CHCl3/MeOH) to afford tert-butyl 4-(2-oxoindolin-5-yl)piperidine-1-carboxylate (846 mg, 92%).
Reaction SMILES: Cl[C:2]1[CH:10]=[C:9]2[C:5]([C:6](=N)[N:7]3[C:14](=[O:15])[C:13]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:12][C:11]([C:22]([OH:24])=[O:23])=[C:8]32)=[CH:4][CH:3]=1.C([O-])=O.[NH4+]>CO.[Pd]>[O:15]=[C:14]1[N:7]2[CH2:6][C:5]3[C:9]([C:8]2=[C:11]([C:22]([OH:24])=[O:23])[CH:12]=[C:13]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[CH:10][CH:2]=[CH:3][CH:4]=3
Reactant: N=C1c2ccc(Cl)cc2-c2c(C(=O)O)cc(-c3ccccc3)c(=O)n21
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CO
Product: O=C(O)c1cc(-c2ccccc2)c(=O)n2c1-c1ccccc1C2
Yield: 80.2 %

Procedure:
A suspension of 18.1 g of 9-chloro-6-imino-4-oxo-3-phenyl-6H-pyrido[2,1-a]isoindole-1-carboxylic acid and 18 g of 10 percent palladium/carbon in 900 ml of methanol was treated with 16.3 g of ammonium formate and then heated to boiling under reflux for 90 minutes. The treatment with ammonium formate and subsequent heating were repeated once, whereupon the catalyst was filtered off, the solvent was removed in a vacuum and the residue was taken up in 150 ml of water. The mixture was acidified with 1N hydrochloric acid, the crystals were filtered off under suction and washed with water. There were obtained 12.55 g of 4,6-dihydro-4-oxo-3-phenylpyrido[2,1-a]isoindole-1-carboxylic acid with a m.p. of 277°-278° (decomposition).
Reaction SMILES: [CH:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[CH:5][CH:4]=1)=[O:2].[CH2:12]([Mg]Br)[CH2:13][CH3:14].Cl>O1CCCC1>[OH:2][CH:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[CH:5][CH:4]=1)[CH2:12][CH2:13][CH3:14]
Reactant: O=Cc1ccc(C(=O)O)cc1
Reactant: CCC[Mg]Br
Agent: Cl
Solvent: C1CCOC1
Product: CCCC(O)c1ccc(C(=O)O)cc1
Reaction time: 0.25 h

Procedure:
6 g of 4-formylbenzoic acid is dissolved in 100 ml of tetrahydrofuran and mixed with 100 ml of a 1-molar solution of propyl magnesium bromide in tetrahydrofuran. After 6 hours of reaction time at room temperature the mixture is stirred into 100 ml of 2M of hydrochloric acid, extracted with ether and the ether phase is concentrated by evaporation. The crystalline material is filtered off with toluene on a suction filter and dissolved in 45 ml of dioxane and 5 ml of water and treated with 1.5 g of sodium boron hydride. After 15 minutes at room temperature, the mixture is added to 1M of hydrochloric acid, extracted with ethyl acetate, dried, concentrated by evaporation and chromatographed on 120 g of silica gel [toluene/acetic acid/water (10:10:1); upper phase after addition of a little water)]. 4.04 g of 4-(1-hydroxybutyl)-benzoic acid with a melting point of 109°-113° C. is obtained.
Reaction SMILES: [ClH:1].[NH2:2][C:3]1[NH:7][C:6]2[CH:8]=[C:9]([N:12]3[C:16](=[O:17])[CH:15]=[CH:14][C:13]3=[O:18])[CH:10]=[CH:11][C:5]=2[N:4]=1.N[C:20]1C=CC2N=C(N(C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)N(C(OC(C)(C)C)=O)C=2C=1.C1(=O)OC(=O)CCC1>>[ClH:1].[NH2:2][C:3]1[NH:7][C:6]2[CH:8]=[C:9]([N:12]3[C:13](=[O:18])[CH2:20][CH2:14][CH2:15][C:16]3=[O:17])[CH:10]=[CH:11][C:5]=2[N:4]=1
Reactant: Nc1nc2ccc(N3C(=O)C=CC3=O)cc2[nH]1
Reactant: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)c1nc2ccc(N)cc2n1C(=O)OC(C)(C)C
Agent: Cl
Agent: O=C1CCCC(=O)O1
Product: Nc1nc2ccc(N3C(=O)CCCC3=O)cc2[nH]1
Yield: 93 %

Procedure:
Following the same procedure to synthesize 1-(2-amino-1H-benzo[d]imidazol-6-yl)-1H-pyrrole-2,5-dione hydrochloride, tert-butyl 6-amino-2-(bis(tert-butoxycarbonyl)amino)-1H-benzo[d]imidazole-1-carboxylate (0.113 g, 0.252 mmol) was reacted with glutaric anhydride (0.029 g, 0.252 mmol) to give the title compound (0.066 g, 93% yield) as a white solid. 1H NMR (300 MHz, CD3OD) δ 7.85 (s, 1H), δ 7.28 (s, 2H), δ 2.42 (m, 4H), δ 1.97 (m, 2H) ppm; 13C NMR (75 MHz, CD3OD) δ 174.1, 172.6, 135.2, 129.8, 125.9, 103.6, 35.6, 32.9, 20.9 ppm; HRMS (ESI) Calcd for C12H12N4O2 (M+) 244.0960. Found 244.0969.
Reaction SMILES: [CH2:1]([N:8]=[N+:9]=[N-:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:11]([OH:18])(=[O:17])[CH2:12][CH2:13][CH2:14][C:15]#[CH:16].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+].[Cl-].[Na+]>C(O)(C)(C)C.O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.CCOC(C)=O>[CH2:1]([N:8]1[CH:16]=[C:15]([CH2:14][CH2:13][CH2:12][C:11]([OH:18])=[O:17])[N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [N-]=[N+]=NCc1ccccc1
Reactant: C#CCCCC(=O)O
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: O=C1O[C@H]([C@@H](O)CO)C([O-])=C1O
Solvent: CC(C)(C)O
Solvent: O
Solvent: CCOC(C)=O
Product: O=C(O)CCCc1cn(Cc2ccccc2)nn1
Reaction time: 72 h

Procedure:
Benzyl azide (2.82 ml, 21.18 mmol) was dissolved in tert-butanol (212 ml) and water (212 ml). Hex-5-ynoic acid (2.337 ml, 21.18 mmol) was added followed by copper (II) acetate (385 mg, 2.118 mmol) and sodium L-ascorbate (837 mg, 4.24 mmol) and the reaction mixture was stirred vigorously for 72 hrs. Sodium chloride (solid) was added to the reaction mixture followed by EtOAc (100 ml). The phases separated and the aqueous layer was further extracted with EtOAc. The organics phases were combined, dried over MgSO4 (anh), filtered and evaporated under reduced pressure to afford the title compound;
Reaction SMILES: [CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C:8](=[O:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)[CH2:6]1)=[O:4].[Cl:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22]O>>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C:8](=[O:10])[N:7]([C:11]2[CH:12]=[CH:13][C:14]([O:17][CH2:22][C:21]3[CH:24]=[CH:25][CH:26]=[C:19]([Cl:18])[CH:20]=3)=[CH:15][CH:16]=2)[CH2:6]1)=[O:4]
Reactant: OCc1cccc(Cl)c1
Reactant: COC(=O)[C@@H]1CC(=O)N(c2ccc(O)cc2)C1
Product: COC(=O)[C@@H]1CC(=O)N(c2ccc(OCc3cccc(Cl)c3)cc2)C1

Procedure:
In an analogous manner to that described in Example 28b), the alkylation of the (R)-1-(4-hydroxy-phenyl)-5-oxo-pyrrolidine-3-carboxylic acid methyl ester [Example 28a)] with 3-chlorobenzylalcohol yields the (R)-1-[4-(3-chloro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid methyl ester as a white solid. MS: m/e=360 (M+H)+.
Reaction SMILES: [C:1]1([C:7]2[N:11]([S:12]([C:15]3[S:16][CH:17]=[CH:18][CH:19]=3)(=[O:14])=[O:13])[CH:10]=[C:9]([CH:20]=O)[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CO.[CH3:24][NH2:25].[BH4-].[Na+].[ClH:28].C(=O)([O-])O.[Na+]>CO>[ClH:28].[CH3:24][NH:25][CH2:20][C:9]1[CH:8]=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:11]([S:12]([C:15]2[S:16][CH:17]=[CH:18][CH:19]=2)(=[O:14])=[O:13])[CH:10]=1
Reactant: O=Cc1cc(-c2ccccc2)n(S(=O)(=O)c2cccs2)c1
Reactant: CN
Agent: Cl
Agent: O=C([O-])O
Agent: [BH4-]
Solvent: CO
Product: CNCc1cc(-c2ccccc2)n(S(=O)(=O)c2cccs2)c1
Reaction time: 0.5 h
Yield: 82 %

Procedure:
5-Phenyl-1-(2-thienylsulfonyl)-1H-pyrrole-3-carbaldehyde (180 mg) was dissolved in methanol (20 mL), a 40% methylamine methanol solution (220 mg) was added at room temperature, and the mixture was stirred for 30 min. Sodium borohydride (64 mg) was added at room temperature, and the mixture was stirred for 10 min. 1 mol/L Hydrochloric acid (20 mL) was added, and the mixture was stirred for 5 min. The reaction mixture was alkalized with a saturated aqueous sodium hydrogencarbonate solution and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (eluent: hexane-ethyl acetate=1:4→0:1), and dissolved in ethyl acetate (5 mL). A 4 mol/L hydrogen chloride-ethyl acetate solution (1 mL) was added, and the mixture was concentrated under reduced pressure. The residue was crystallized from ethyl acetate to give the title compound as colorless crystals (yield 171 mg, 82%).