Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[CH:10]=[CH:9][CH:8]=[CH:7][C:4]=1[CH:5]=O.C[O-].[K+].[CH2:16]([N:23]1[CH2:28][CH2:27][CH:26]([CH:29]=[O:30])[CH2:25][CH2:24]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CO>[CH2:16]([N:23]1[CH2:28][CH2:27][CH:26]([C:29](=[O:30])[CH2:5][C:4]2[CH:7]=[CH:8][CH:9]=[CH:10][C:3]=2[C:2]([F:12])([F:11])[F:1])[CH2:25][CH2:24]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=Cc1ccccc1C(F)(F)F
Reactant: O=CC1CCN(Cc2ccccc2)CC1
Agent: C[O-]
Agent: [K+]
Solvent: CO
Product: O=C(Cc1ccccc1C(F)(F)F)C1CCN(Cc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 48.7 %

Procedure:
After dissolving 2.57 g of 2-(trifluoromethyl)benzaldehyde in 15 ml of methanol, 2.75 g of p-toluenesulfonyl hydrazide was added, the mixture was stirred at room temperature for 2 hours, and then 1.09 g of potassium methoxide and a methanol solution (4 ml) of 1.50 g of 1-benzylpiperidine-4-carboxaldehyde was added, and the mixture saws shielded from light and stirred overnight at 55° C. The reaction solution was concentrated under reduced pressure, water was added, and extraction was performed with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue fleas purified by silica gel column chromatography (solvent: toluene/ethyl acetate) to obtain the title compound (1.30 g, 49% yield).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([NH2:12])=[S:11])=[CH:5][CH:4]=1.CC1[O:19][C:18](=O)[CH2:17][C:16](C)([CH3:21])O1.O1C=COCC1=O>C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]2[C:16]([CH3:21])=[CH:17][C:18](=[O:19])[NH:12][C:10]2=[S:11])=[CH:7][CH:8]=1
Reactant: CC1OC(=O)CC(C)(C)O1
Reactant: COc1ccc(NC(N)=S)cc1
Agent: O=C1COC=CO1
Solvent: CCO
Product: COc1ccc(-n2c(C)cc(=O)[nH]c2=S)cc1
Temperature: 140 °C
Reaction time: 0.17 h
Yield: 72.2 %

Procedure:
N-(4-Methoxyphenyl)thiourea (18.2 g, 100 mM) and 2,6,6-trimethyl-1,3-dioxin-4-one (21.3 g, 150 mM) were heated together at 140° C. (bath temperature) for 30 minutes. The solid product was cooled, treated with ethanol (100 ml), boiled for 10 minutes, cooled and the solid product was isolated by filtration. More dioxinone (21.3 g) was added to the above material and the mixture was heated at 140° C. for a further 20 minutes. Ethanol (50 ml) was then added to the cooled mixture, which was then heated under reflux for 5 minutes. The mixture was cooled and the solid product isolated by filtration to give 2,3-dihydro-1-(4-methoxyphenyl)-6-methyl-2-thioxo-4(1H)pyrimidinone (17.9 g, 72% yield) m.p. 248°-249° C.; microanalysis, found: C,58.2; H,4.9; N,11.0%; C12H12N2OS requires: C,58.1; H,4.8; N,11.3%.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([CH2:12]/[CH:13]=[CH:14]/[C:15]2[CH:24]=[CH:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH:16]=2)[C@@H:9](O)[CH3:10])=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.C1(P([N:70]=[N+:71]=[N-:72])(C2C=CC=CC=2)=O)C=CC=CC=1>O1CCCC1>[N-:70]=[N+:71]=[N-:72].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH2:9][CH3:10])[CH2:12][CH:13]=[CH:14][C:15]2[CH:24]=[CH:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH:16]=2)=[CH:4][CH:3]=1
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: C[C@H](O)[C@@H](C/C=C/c1ccc2ccccc2c1)c1ccc(Cl)cc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCC(CC=Cc1ccc2ccccc2c1)c1ccc(Cl)cc1
Product: [N-]=[N+]=[N-]

Procedure:
1.81 g of the alcohol thus obtained was dissolved in 18 ml of tetrahydrofuran, and 2.11 g of triphenylphosphine, 1.27 ml of diethyl azodicarboxylate and 1.73 g of diphenylphosphoryl azide were added under cooling with ice under stirring, followed by stirring at room temperature for 30 minutes. The reaction solution was evaporated to dryness under reduced pressure, and then the residue was purified by silica gel column chromatography (hexane/ethyl acetate=50/1) to obtain 1.59 g of (4S*,5S*,5E)-5-azide-4-(4-chlorophenyl)-1-(2-naphthyl)-1-hexene.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH2:15][CH:14]3[N:16]([CH3:17])[CH:10]([CH2:11][CH2:12][CH2:13]3)[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:18]([O:21][C:22](=[O:24])[CH3:23])(=[O:20])[CH3:19]>ClCCl>[C:18]([OH:21])(=[O:20])[CH3:19].[C:22]([NH:1][C:2]1[CH:3]=[C:4]([C:8]2[CH2:9][CH:10]3[N:16]([CH3:17])[CH:14]([CH2:13][CH2:12][CH2:11]3)[CH:15]=2)[CH:5]=[CH:6][CH:7]=1)(=[O:24])[CH3:23]
Reactant: CC(=O)OC(C)=O
Reactant: CN1C2C=C(c3cccc(N)c3)CC1CCC2
Solvent: ClCCl
Product: CC(=O)Nc1cccc(C2=CC3CCCC(C2)N3C)c1
Product: CC(=O)O

Procedure:
To a solution of (±)-3-(3-aminophenyl)-9-methyl-9-azabicyclo[3.3.1]non-2-ene (0.43 g, 1.9 mmol) in dichloromethane was added dropwise, Acetic Acid anhydride (0.25 g, 0.23 ml) at 0° C. The mixture was triturated with petroleum ether (2×10 ml), followed by diethyl ether (10 ml). Yield 0.34 g, 55%. Mp. 59.9-63.4° C.
Reaction SMILES: C[O-].[Na+].C(OC(=O)C([O:10][CH2:11][CH3:12])=O)C.[N+:14]([C:17]1C=[CH:21][CH:20]=[CH:19][C:18]=1C)([O-:16])=[O:15].O>C(O)C>[N+:14]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:12]=1[CH:11]=[O:10])([O-:16])=[O:15]
Reactant: CCOC(=O)C(=O)OCC
Reactant: Cc1ccccc1[N+](=O)[O-]
Agent: C[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: O=Cc1ccccc1[N+](=O)[O-]
Temperature: 40 °C
Reaction time: 1.5 h

Procedure:
383 g (7.1 mols) of sodium methylate are dissolved in ethanol and 985 g (6.75 mols) of oxalic acid diethyl ester and 925 g (6.75 mols) of 2-nitrotoluene are poured in. The mixture is heated under reflux for 30 minutes and is allowed to cool, 300 ml of ice water are next added cautiously and after the exothermic reaction has subsided 1,600 ml of water are added. After boiling additionally for 90 minutes under reflux, the mixture is steam-distilled until two phases no longer pass over. The organic phase is separated from the distillate and 310 g of 2-nitrotoluene are recovered from it. The residual aqueous phase of the distillate is filtered, 600 g of (anhydrous) sodium carbonate and 2,000 ml of toluene are added and the mixture is cooled to +3° C. 650 g of solid potassium permanganate are added over the course of 70 minutes and the reaction temperature is kept at between +2° and +6° C. The mixture is stirred for a further 45 minutes at +5° C and then warmed to 40° C, and 50% strength sulphuric acid is then added dropwise (gas being evolved). The exothermic reaction is kept at 35°- 40° C by cooling. Insoluble material is then filtered off and the toluene phase is separated from the filtrate. The filter residue is washed with hot toluene and the combined toluene phases are extracted by shaking with 15% strength sodium carbonate solution and with water and are then dried with the sodium sulphate. On concentrating the toluene phase in vacuo, 2-nitrobenzaldehyde is obtained as a viscous oil which crystallizes immediately on cooling. Melting point 40°- 41° C.
Reaction SMILES: [OH:1][CH2:2][C:3]([C@H:5]([C@@H:7]([C@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])=[O:4].[O:13]=[O:14]>>[OH:12][CH2:11][C:9]([C@H:7]([C@@H:5]([C:3]([CH2:2][OH:1])=[O:4])[OH:6])[OH:8])=[O:10].[OH:13][OH:14]
Reactant: O=O
Reactant: O=C(CO)[C@@H](O)[C@H](O)[C@@H](O)CO
Product: O=C(CO)[C@@H](O)[C@H](O)C(=O)CO
Product: OO

Procedure:
For these enzymes, glucose oxidase catalyzes the reaction of β-D-glucose, water, and oxygen to produce hydrogen peroxide and gluconic acid. Galactose oxidase catalyzes the reaction of D-galactose and oxygen to produce hydrogen peroxide and D-galacto-hexodialdose. Urate oxidase catalyzes the reaction of uric acid, water, and oxygen to produce hydrogen peroxide, allantoin, and carbon dioxide. Choline oxidase catalyzes the reaction of choline and oxygen to produce hydrogen peroxide and betaine aldehyde. D-amino acid oxidase catalyzes the reaction of D-amino acids such as D-proline, D-methionine, D-isoleucine, D-alanine, D-valine, or D-phenylalanine with water and oxygen to produce hydrogen peroxide, ammonia, and the α-keto acid corresponding to the D-amino acid being oxidized. D-glutamate oxidase catalyzes the reaction of D-glutamic acid, water, and oxygen to produce hydrogen peroxide, ammonia, and 2-ketoglutarate. Glycine oxidase catalyzes the reaction of glycine, water, and oxygen to produce hydrogen peroxide, ammonia, and glyoxylic acid. Glycolic acid oxidase (also known as 2-hydroxyacid oxidase) catalyzes the reaction of glycolic acid and oxygen to produce 2-ketoacetic acid and hydrogen peroxide. L-sorbose oxidase catalyzes the reaction of L-sorbose and oxygen to produce 5-dehydro-D-fructose and hydrogen peroxide. Alcohol oxidase catalyzes the reaction of a lower primary alcohol or an unsaturated alcohol and oxygen to produce the corresponding aldehyde and hydrogen peroxide. Amine oxidase catalyzes the reaction of an amine, typically a primary amine, but also, in some cases, a secondary or tertiary amine, water, and oxygen to produce the corresponding aldehyde, ammonia, and hydrogen peroxide. In an illustrative reaction, glucose oxidase catalyzes the reaction of β-D-glucose, water, and oxygen during application to the outer ear to produce hydrogen peroxide and gluconic acid.
Reaction SMILES: [CH3:1][CH:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[CH2:4][CH2:3]1.C(O[CH:16](OCC)[N:17]([CH3:19])[CH3:18])C>>[CH3:16][N:17]([CH:19]=[C:4]1[CH2:3][CH:2]([CH3:1])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]1=[O:12])[CH3:18]
Reactant: CCOC(OCC)N(C)C
Reactant: CC1CCC(=O)c2ccccc21
Product: CC1CC(=CN(C)C)C(=O)c2ccccc21

Procedure:
The 3,4-dihydro-2-(dimethylaminomethylene)-4-methyl-1(2H)-naphthalenone starting material was prepared from 4-methyl-1-tetralone (4.0 g, 25 mmol) and N,N-dimethylformamide diethyl acetal (17 ml, 100 mmol) to give the desired product as a thick yellow oil (4.53 g). δH (CDCl3) 8.03 (1H, dd, J 7.7, 1.5 Hz), 7.77 (1H, s), 7.39 (1H, td, J 7.4, 1.5 Hz), 7.29 (1H, td, J 7.5, 1.3 Hz), 7.20 (1H, dm, J 7.5 Hz), 3.12 (6H, s), 3.10-2.90 (2H, m), 2.75 (1H, apparent q, 6.9 Hz) and 1.30 (3H, d, J 6.9 Hz). MS (ES+) 216 (MH+, 100%).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[N:7][C:8]([CH3:15])=[C:9]([O:12][CH2:13][CH3:14])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:16]([O:18][CH2:19][CH3:20])=[O:17].[NH2:21][C:22]1[CH:23]=[CH:24][C:25]([O:28][CH2:29][CH3:30])=[N:26][CH:27]=1>>[ClH:1].[CH2:13]([O:12][C:9]1[CH:10]=[C:11]2[C:6](=[N:7][C:8]=1[CH3:15])[N:5]=[CH:4][C:3]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[C:2]2[NH:21][C:22]1[CH:23]=[CH:24][C:25]([O:28][CH2:29][CH3:30])=[N:26][CH:27]=1)[CH3:14]
Reactant: CCOC(=O)c1cnc2nc(C)c(OCC)cc2c1Cl
Reactant: CCOc1ccc(N)cn1
Product: CCOC(=O)c1cnc2nc(C)c(OCC)cc2c1Nc1ccc(OCC)nc1
Product: Cl

Procedure:
A mixture of ethyl 4-chloro-6-ethoxy-7-methyl-1,8-naphthyridine-3-carboxylate (2.4 g), 5-amino-2-ethoxypyridine (1.15 g) and IMS (50 ml) was boiled under reflux for 1.5 hours. The mixture was cooled and filtered to give ethyl 6-ethoxy-4-(2-ethoxy-5-pyridylamino)-7-methyl-1,8-naphthyridine-3-carboxylate hydrochloride, m.p. 221°-223° C. Active (1/1) at 30 mg/kg.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:6]=[N:7][C:8]([N:11]2[CH2:23][CH2:22][C:21]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:13]=3[CH2:12]2)=[N:9][CH:10]=1)=O.[H-].C([Al+]CC(C)C)C(C)C.CO.O>C(Cl)Cl>[OH:2][CH2:3][C:5]1[CH:6]=[N:7][C:8]([N:11]2[CH2:23][CH2:22][C:21]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:13]=3[CH2:12]2)=[N:9][CH:10]=1
Reactant: COC(=O)c1cnc(N2CCc3c(n(C(=O)OC(C)(C)C)c4ccccc34)C2)nc1
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: ClCCl
Solvent: CO
Solvent: O
Product: CC(C)(C)OC(=O)n1c2c(c3ccccc31)CCN(c1ncc(CO)cn1)C2
Yield: 75.6 %

Procedure:
To a stirred solution of tert-butyl 2-[5-(methoxycarbonyl)pyrimidin-2-yl]-1,2,3,4-tetrahydro-9H-b-carboline-9-carboxylate (3.0 g, 0.0073 moles) in dry DCM (30 mL) was added diisobutyl aluminum hydride (14.7 mL, 0.022 moles, 1.5N in DCM) at −78° C. The temperature was slowly allowed to rise to −25° C. and continued the stirring for further 6.0 hours. After completion of the reaction, MeOH (20 mL) and water (20 mL) was added to the reaction and allowed to come to room temperature. The reaction mixture was then extracted using DCM. The combined organic layer was washed with water (20 mL), brine (20 ml), dried (Na2SO4) and concentrated. The compound was purified by recrystallization using mixture of diethyl ether and hexane to give pure tert-butyl 2-[5-(hydroxymethyl)pyrimidin-2-yl]-1,2,3,4-tetrahydro-9H-b-carboline-9-carboxylate (2.1 g, 75% yield). Rf=0.3. 1H NMR (DMSO-d6, 400 MHz) ppm: 8.38 (s, 2H, 2Ar—H), 8.05 (d, 1H, J=8 Hz, 1—H), 7.49 (d, 1H, J=8 Hz, 1Ar—H), 7.31-7.22 (m, 2H, 2Ar—H), 5.15 (s, 2H, CH2), 5.10 (t, 1H, J=8 Hz, OH), 4.34 (d, 2H, J=8 Hz, CH2), 4.11 (t, 2H, CH2), 2.75 (brs, 2H, CH2), 1.68 (s, 9H, 3CH3). M/e=381 (M+1) (M, 380.440 Calcd. for C21H24N4O3).
Reaction SMILES: C([NH:5][C:6]1[N:11]=[C:10]([N:12]2[C:21]3[C:16](=[CH:17][C:18]([F:24])=[C:19]([F:23])[C:20]=3[Cl:22])[C:15](=[O:25])[CH:14]([C:26]([O:28]CC)=[O:27])[C:13]2=[O:31])[C:9]([C:32]#[N:33])=[CH:8][C:7]=1[F:34])(C)(C)C.Cl>>[NH2:5][C:6]1[N:11]=[C:10]([N:12]2[C:21]3[C:16](=[CH:17][C:18]([F:24])=[C:19]([F:23])[C:20]=3[Cl:22])[C:15](=[O:25])[CH:14]([C:26]([OH:28])=[O:27])[C:13]2=[O:31])[C:9]([C:32]#[N:33])=[CH:8][C:7]=1[F:34]
Reactant: CCOC(=O)C1C(=O)c2cc(F)c(F)c(Cl)c2N(c2nc(NC(C)(C)C)c(F)cc2C#N)C1=O
Agent: Cl
Product: N#Cc1cc(F)c(N)nc1N1C(=O)C(C(=O)O)C(=O)c2cc(F)c(F)c(Cl)c21
Yield: 51.6 %

Procedure:
To 280 mg of ethyl 1-(6-t-butylamino-3-cyano-5-fluoropyridine-2-yl)-8-chloro-6,7-difluoro-1,4-dihydro-4-oxoquinolone-3-carboxylate was added 3 ml of 12N hydrochloric acid, and the mixture was heated under reflux for 6 hours and allowed to cool. The solid precipitate was collected by filtration and washed with ethanol and diethylether successively to obtain 120 mg of the title compound as a pale yellow powder.
Reaction SMILES: [O:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[N+:10]([O-])([OH:12])=[O:11].[OH-].[Na+]>S(=O)(=O)(O)O.O>[N+:10]([C:6]1[N:5]=[C:4]2[CH2:3][CH2:2][O:1][C:9]2=[CH:8][CH:7]=1)([O-:12])=[O:11]
Reactant: c1cnc2c(c1)OCC2
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=[N+]([O-])c1ccc2c(n1)CCO2
Temperature: 25 °C
Reaction time: 1 h
Yield: 83 %

Procedure:
To a solution of 2,3-dihydrofuro[3,2-b]pyridine (32.9 g, 271 mmol) in sulfuric acid (50 mL) was added dropwise a mixed solution of fuming nitric acid (20 mL) and sulfuric acid (20 mL) under ice-cooling, and the mixture was stirred at room temperature for 1 hr. The reaction solution was neutralized with 8M aqueous sodium hydroxide solution and diluted with water. The resulting crystals were collected by filtration to give the title compound (37.5 g, yield 83%).
Reaction SMILES: CS(Cl)(=O)=O.[Br:6][C:7]1[CH:11]=[C:10]([C:12]([OH:14])=O)[N:9]([C:15]2[C:20]([Cl:21])=[CH:19][CH:18]=[CH:17][N:16]=2)[N:8]=1.C(N(CC)CC)C.[NH2:29][C:30]1[C:38]([CH3:39])=[CH:37][C:36]([I:40])=[CH:35][C:31]=1[C:32](O)=[O:33]>C(#N)C.O>[Br:6][C:7]1[CH:11]=[C:10]([C:12]2[O:14][C:32](=[O:33])[C:31]3[CH:35]=[C:36]([I:40])[CH:37]=[C:38]([CH3:39])[C:30]=3[N:29]=2)[N:9]([C:15]2[C:20]([Cl:21])=[CH:19][CH:18]=[CH:17][N:16]=2)[N:8]=1
Reactant: Cc1cc(I)cc(C(=O)O)c1N
Reactant: O=C(O)c1cc(Br)nn1-c1ncccc1Cl
Agent: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: CC#N
Product: Cc1cc(I)cc2c(=O)oc(-c3cc(Br)nn3-c3ncccc3Cl)nc12
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
To a solution of methanesulfonyl chloride (0.54 ml, 6.94 mmol) in acetonitrile (15 mL) was added dropwise a mixture of 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid (i.e. the carboxylic acid product of Step D) (2.0 g, 6.6 mmol) and triethylamine (0.92 ml, 6.6 mmol) in acetonitrile (5 mL) at 0° C. The reaction mixture was then stirred for 15 minutes at 0° C. Then, 2-amino-3-methyl-5-iodobenzoic acid (i.e. the product from Example 1, Step A) (1.8 g, 6.6 mmol) was added, and stirring was continued for an additional 5 minutes. A solution of triethylamine (1.85 mL, 13.2 mmol) in acetonitrile (5 mL) was then added dropwise while keeping the temperature below 5° C. The reaction mixture was stirred 40 minutes at 0° C., and then methanesulfonyl chloride (0.54 ml, 6.94 mmol) was added. The reaction mixture was then warmed to room temperature and stirred overnight. The reaction mixture was then diluted with water (50 mL) and extracted with ethyl acetate (3×50 mL). The combined ethyl acetate extracts were washed successively with 10% aqueous sodium bicarbonate (1×20 mL) and brine (1×20 mL), dried (MgSO4) and concentrated to afford 2.24 g of the title product as a crude yellow solid.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[NH:14][C:13]([CH2:18][OH:19])=[CH:12]3)[CH2:5][CH2:4][CH2:3][CH2:2]1>ClCCl.C1(C)C=CC=CC=1.[O-2].[Mn+4].[O-2]>[N:1]1([CH2:6][CH2:7][CH2:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[NH:14][C:13]([CH:18]=[O:19])=[CH:12]3)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: OCc1cc2cc(CCCN3CCCC3)ccc2[nH]1
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: O=Cc1cc2cc(CCCN3CCCC3)ccc2[nH]1
Temperature: 25 °C
Reaction time: 8 h
Yield: 72.6 %

Procedure:
Manganese (IV) oxide (4.7 g, 54 mmol) was added to a mixture of [5-(3-pyrrolidin-1-yl-propyl)-1H-indol-2-yl]-methanol (940 mg, 3.6 mmol) in dichloromethane (150 mL) and toluene (150 mL). The mixture was stirred at room temperature for overnight. The reaction was filtered through a pad of celite and the filtrate was concentrated to give 670 mg (72%) of 5-(3-pyrrolidin-1-yl-propyl)-1H-indole-2-carbaldehyde.
Reaction SMILES: [NH2:1][NH:2][C:3]([NH2:5])=[S:4].[CH2:6](Cl)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(O)C.[N:17]([O-])=O.[Na+]>C(OCC)(=O)C.O>[CH2:6]([S:4][C:3]1[NH:5][N:17]=[N:1][N:2]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: ClCc1ccccc1
Reactant: O=N[O-]
Reactant: NNC(N)=S
Agent: [Na+]
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: O
Product: c1ccc(CSc2nnn[nH]2)cc1
Reaction time: 0.25 h

Procedure:
A solution of 30 g. (0.33 mole) of thiosemicarbazide and 51 g. (0.40 mole) of benzyl chloride in 500 ml. of ethyl alcohol was heated at the reflux temperature for about 3.5 hours. After heating, the reaction mixture was evaporated to dryness under reduced pressure and the residue was dissolved in water. The solution was washed with ethyl acetate and was added to a solution of 25 g. (0.36 mole) of sodium nitrite in 50 ml. of water. The solution was stirred for 15 minutes and then ethyl acetate was added. The organic layer was separated and washed with water, brine, and was dried over sodium sulfate. The dried ethyl acetate solution was evaporated under reduced pressure, and the product obtained as a residue was washed with methylene chloride and recrystallized from ethyl acetate. There were obtained 21 g. of the product melting at about 134° C. to about 136° C.
Reaction SMILES: [NH3:1].S(O[CH2:13][CH:14]1[CH2:22][CH2:21][C:17]2[N:18]=[CH:19][S:20][C:16]=2[CH2:15]1)(C1C=CC(C)=CC=1)(=O)=O>CO>[NH2:1][CH2:13][CH:14]1[CH2:22][CH2:21][C:17]2[N:18]=[CH:19][S:20][C:16]=2[CH2:15]1
Reactant: N
Reactant: Cc1ccc(S(=O)(=O)OCC2CCc3ncsc3C2)cc1
Solvent: CO
Product: NCC1CCc2ncsc2C1
Yield: 42 %

Procedure:
The compound is prepared by action of ammonia on the above tosylate (V), in methanol, in a autoclave at 100° C. B.p.0.5 =100°-106° C. Yield: 42%.
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]#[N:5].[CH2:6]=O.[CH:8]1[CH2:12][CH:11]=[CH:10][CH:9]=1>O.C(Cl)Cl>[CH:9]12[CH2:8][CH:12]([CH:11]=[CH:10]1)[CH2:6][N:5]2[CH2:4][C:3]#[N:2]
Reactant: C1=CCC=C1
Reactant: C=O
Reactant: N#CCN
Agent: Cl
Solvent: ClCCl
Solvent: O
Product: N#CCN1CC2C=CC1C2
Reaction time: 0.5 h

Procedure:
A solution of aminoacetonitrile hydrochloride (18.5 g, 0.20 mol) in water at 5° C. is treated with 37% formalin (23.0 g, 0.28 mol formaldehyde) followed by cyclopentadiene (26.0 g, 0.4 mol), stirred at 5°-10° C. for 30 minutes and diluted with methylene chloride. The phases are separated, the aqueous phase is extracted with methylene chloride and basified to pH >12 with 10% NaOH. The aqueous basic phase is extracted with methylene chloride. The methylene chloride extract of the basic aqueous phase is concentrated in vacuo to give the title product (N-cyanomethylazanorbornene), 22.7 g, which can be distilled at 68°-70° C./0.55 torr. The compound is identified by NMR and mass spectral analyses.
Reaction SMILES: [CH2:1]([C:3]1[N:7]([CH3:8])[C:6]2[CH:9]=[C:10]([N:13]3[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][C:14]3=[O:20])[CH:11]=[CH:12][C:5]=2[N:4]=1)[CH3:2].[Cl:21][C:22]1[CH:23]=[C:24]([CH2:27]O)[S:25][CH:26]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1>[Cl:21][C:22]1[CH:23]=[C:24]([CH2:27][O:19][C:16]2[CH:17]=[CH:18][N:13]([C:10]3[CH:11]=[CH:12][C:5]4[N:4]=[C:3]([CH2:1][CH3:2])[N:7]([CH3:8])[C:6]=4[CH:9]=3)[C:14](=[O:20])[CH:15]=2)[S:25][CH:26]=1
Reactant: OCc1cc(Cl)cs1
Reactant: CCc1nc2ccc(-n3ccc(O)cc3=O)cc2n1C
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: C1CCOC1
Product: CCc1nc2ccc(-n3ccc(OCc4cc(Cl)cs4)cc3=O)cc2n1C
Temperature: 60 °C
Reaction time: 4 h

Procedure:
To a solution of 1-(2-ethyl-1-methyl-1H-benzimidazol-6-yl)-4-hydroxypyridin-2(1H)-one (150 mg), (4-chloro-thiophen-2-yl)methanol (167 mg) and tributylphosphine (338 mg) in THF (15 ml) was added 1,1′-(azodicarbonyl)dipiperidine (422 mg), and the mixture was stirred under at 60° C. for 4 h. The reaction mixture was then cooled to room temperature, and concentrated in vacuo. The residue was diluted with DCM, washed with water and brine successively, dried over Na2SO4, concentrated in vacuo, and purified by silica gel column chromatography (MeOH/DCM) to afford the title compound as a white solid.
Reaction SMILES: [C:1]1([S:7]([N:10]=[C:11]=[O:12])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH:13][CH2:14][CH2:15][C:16]1[CH:24]=[CH:23][CH:22]=[C:21]2[C:17]=1[CH2:18][C:19](=[O:25])[NH:20]2.[OH-].[Na+]>O1CCCC1.CN(C)C=O.N1C=CC=CC=1>[O:25]=[C:19]1[CH2:18][C:17]2[C:21](=[CH:22][CH:23]=[CH:24][C:16]=2[CH2:15][CH2:14][O:13][C:11](=[O:12])[NH:10][S:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)(=[O:8])=[O:9])[NH:20]1
Reactant: O=C=NS(=O)(=O)c1ccccc1
Reactant: O=C1Cc2c(CCO)cccc2N1
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: O=C1Cc2c(CCOC(=O)NS(=O)(=O)c3ccccc3)cccc2N1
Temperature: 80 °C
Yield: 27.1 %

Procedure:
Benzene sulfonyl isocyanate (1.07 mL, 8 mmol) was added dropwise to a stirred mixture of 4-(2-hydroxy-ethyl)-1,3-dihydro-indol-2-one (709 mg, 4 mmol) in tetrahydrofuran (8 mL), dimethylforamide (2 mL) and pyridine (3 drops) under nitrogen atmosphere. The mixture was heated at 80° C. for 15 hours. The reaction was cooled, poured into 1 N sodium hydroxide solution (100 mL) and extracted with ethyl acetate (200 mL). The organic layer was discarded and the basic aqueous layer was acidified with 6 N hydrochloric acid (18 mL) followed by extraction into ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated. The residue was recrystallized from methanol/ethyl acetate/hexane to give 390 mg (27%) of benzene sulfonyl-carbamic acid 2-(2-oxo-2,3-dihydro-1H-indol-4-yl)-ethyl ester as an off-white powder.