Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=[CH:4][N:3]=1.Cl.C([N:14]=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.C(C(=CC)C=CCN)C>ClCCl.C(=O)([O-])O.[Na+]>[CH3:1][C:2]1[C:7]([C:8]([NH2:14])=[O:10])=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: Cc1ncccc1C(=O)O
Reactant: CCN=C=NCCCN(C)C
Agent: CC=C(C=CCN)CC
Agent: Cl
Agent: O=C([O-])O
Solvent: ClCCl
Product: Cc1ncccc1C(N)=O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 158.1 %

Procedure:
A solution of 2-methyl-3-pyridinecarboxylic acid (1.66 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.12 g), and N-hydroxybenzotriazole (1.63 g) in dichloromethane (25 ml) was stirred at 0° C. for 15 minutes. A solution of 4-ethyl-2,4-hexadien-1-ylamine (1.26 g) in dichloromethane (6.3 ml) was added dropwise to the solution over a period of 10 minutes. The mixture was stirred at 0° C. for 30 minutes and then at room temperature for 3 hours. The reaction mixture was diluted with aqueous sodium hydrogen carbonate. The organic phase separated was washed with water and brine, dried over anhydrous magnesium sulfate, and evaporated in vacuo. The residue was chromatographed on silica gel (4% methanol-chloroform) to give N-[(2E,4E)- and (2Z,4E)-4-ethyl-2,4-hexadien-1-yl]-2-methyl-3-pyridinecarboxamide (2.38 g) as an oil.
Reaction SMILES: [NH:1]1[C@@H:10]2[C@@H:5]([CH2:6][CH2:7][CH2:8][CH2:9]2)[NH:4][CH2:3][C:2]1=[O:11].C([O-])(O)=O.[Na+].[CH2:17]([O:24][C:25](Cl)=[O:26])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>O>[CH2:17]([O:24][C:25]([N:4]1[C@H:5]2[C@H:10]([CH2:9][CH2:8][CH2:7][CH2:6]2)[NH:1][C:2](=[O:11])[CH2:3]1)=[O:26])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: O=C1CN[C@@H]2CCCC[C@@H]2N1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Product: O=C1CN(C(=O)OCc2ccccc2)[C@@H]2CCCC[C@@H]2N1
Temperature: 10 °C
Yield: 97.6 %

Procedure:
(+/−)-cis-Decahydroquinoxalin-2-one (0.8 g, 5.19 mmol) is suspended in 25 ml of H2O. NaHCO3 (0.87 g, 10.35 mmol) is added and the reaction mixture is cooled to 10° C. Benzylchloroformate (1 ml, 6.68 mmol) is added dropwise to the vigorously stirred mixture. After 20 hours at room temperature the solid is filtered, washed thoroughly with H2O, air-dried. The title compound (1.46 g, 98% yield) is obtained as a white solid.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:21]=[CH:20][C:6]([O:7][CH2:8][C:9]2[N:10]=[C:11]([C:15]3[O:16][CH:17]=[CH:18][CH:19]=3)[O:12][C:13]=2[CH3:14])=[C:5]([O:22][CH3:23])[CH:4]=1.[CH2:24]([N:26]1[CH:30]=[C:29]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:28]([OH:36])=[N:27]1)[CH3:25].CN(C)C=O.[H-].[Na+]>O>[CH2:24]([N:26]1[CH:30]=[C:29]([C:31]([O:33][CH2:34][CH3:35])=[O:32])[C:28]([O:36][CH2:2][C:3]2[CH:21]=[CH:20][C:6]([O:7][CH2:8][C:9]3[N:10]=[C:11]([C:15]4[O:16][CH:17]=[CH:18][CH:19]=4)[O:12][C:13]=3[CH3:14])=[C:5]([O:22][CH3:23])[CH:4]=2)=[N:27]1)[CH3:25]
Reactant: CCOC(=O)c1cn(CC)nc1O
Reactant: COc1cc(CCl)ccc1OCc1nc(-c2ccco2)oc1C
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)c1cn(CC)nc1OCc1ccc(OCc2nc(-c3ccco3)oc2C)c(OC)c1
Temperature: 90 °C
Reaction time: 2 h
Yield: 75 %

Procedure:
To a mixture of 4-[(4-chloromethyl-2-methoxyphenoxy)methyl]-2-(2-furyl)-5-methyl-1,3-oxazole (3.50 g), ethyl 1-ethyl-3-hydroxy-1H-pyrazole-4-carboxylate (1.50 g) and N,N-dimethylformamide (30 mL) was added sodium hydride (60% in oil, 0.36 g) at room temperature, and the mixture was stirred at 90° C. for 2 hrs. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give ethyl 1-ethyl-3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1H-pyrazole-4-carboxylate as colorless crystals (2.94 g, yield 75%) from a fraction eluted with ethyl acetate-hexane (2:1, v/v). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 114-115° C.
Reaction SMILES: [CH3:1][N:2]1[C:7](=[O:8])[C:6]2[C:9]([CH2:23][C:24]([OH:26])=O)=[C:10]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:19]([F:22])([F:21])[F:20])[S:11][C:5]=2[N:4]([CH2:27][CH:28]([CH3:30])[CH3:29])[C:3]1=[O:31].[CH3:32][NH:33][CH2:34][CH2:35][OH:36]>CN1CCCC1=O.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>[OH:36][CH2:35][CH2:34][N:33]([CH3:32])[C:24](=[O:26])[CH2:23][C:9]1[C:6]2[C:7](=[O:8])[N:2]([CH3:1])[C:3](=[O:31])[N:4]([CH2:27][CH:28]([CH3:30])[CH3:29])[C:5]=2[S:11][C:10]=1[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C:19]([F:22])([F:20])[F:21]
Reactant: CC(C)Cn1c(=O)n(C)c(=O)c2c(CC(=O)O)c(Cc3ccccc3C(F)(F)F)sc21
Reactant: CNCCO
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN1CCCC1=O
Product: CC(C)Cn1c(=O)n(C)c(=O)c2c(CC(=O)N(C)CCO)c(Cc3ccccc3C(F)(F)F)sc21
Reaction time: 18 h

Procedure:
The product of step b) (98 mg) was dissolved in 1-methyl-2-pyrrolidinone (NMP) (1 ml) to which EDCl (1 ml), HOBT (1 ml) and N-methyl ethanolamine (1 ml) was added. The reaction was stirred for 18 hrs before being concentrated in vacuo. The residue was partitioned between dichloromethane and water. The organic phase was adsorbed onto silica and purified by chromatography eluting with 0-10% methanol in dichloromethane to yield the title compound (62 mg).
Reaction SMILES: Cl.[CH2:2]([NH:7][N:8]=[CH:9][C:10]1[CH:34]=[CH:33][C:13]([C:14]([NH:16][C:17]2[CH:18]=[CH:19][C:20]3[O:25][CH:24]([CH2:26][C:27]([O:29]CC)=[O:28])[CH2:23][CH2:22][C:21]=3[CH:32]=2)=[O:15])=[CH:12][CH:11]=1)[CH2:3][CH2:4][CH2:5][CH3:6].C(O)(=O)C>C(O)C.[OH-].[Na+]>[CH2:2]([NH:7][N:8]=[CH:9][C:10]1[CH:34]=[CH:33][C:13]([C:14]([NH:16][C:17]2[CH:18]=[CH:19][C:20]3[O:25][CH:24]([CH2:26][C:27]([OH:29])=[O:28])[CH2:23][CH2:22][C:21]=3[CH:32]=2)=[O:15])=[CH:12][CH:11]=1)[CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCCNN=Cc1ccc(C(=O)Nc2ccc3c(c2)CCC(CC(=O)OCC)O3)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CCO
Product: CCCCCNN=Cc1ccc(C(=O)Nc2ccc3c(c2)CCC(CC(=O)O)O3)cc1

Procedure:
0.15 g (0.31 mmol) of the ester from Example 94 were stirred overnight at room temperature in a mixture of 10 ml ethanol and 0.7 ml 2 N aqueous sodium hydroxide solution. It was brought to pH 4 with 2 N acetic acid, and the precipitate of the title acid was filtered, washed successively with water and with acetone, and dried in vacuo. Yield: 98 mg (75%) of colorless crystals, m.p. 223-225° C. (dec.).
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1.[CH2:7]([O:9][CH2:10][CH2:11]Cl)[CH3:8].C(N(CC)CC)C>>[CH2:7]([O:9][CH2:10][CH2:11][N:3]1[CH:4]=[CH:5][N:6]=[C:2]1[CH3:1])[CH3:8]
Reactant: CCOCCCl
Reactant: Cc1ncc[nH]1
Solvent: CCN(CC)CC
Product: CCOCCn1ccnc1C
Reaction time: 72 h

Procedure:
In an autoclave of 100 mL, 2-methylimidazole (19.2 g, 200 mmol) was made reacted with chloroethyl ethyl ether (26.0 g, 240 mmol) at 145 deg C. for 72 hours. Brown liquid that was obtained was washed with 120 mL of a compound liquid of ethanol and ether (volume ratio thereof is 1:5), and then made reacted with triethylamine (20.2 g, 200 mmol) in the autoclave of 100 mL at 130 deg C. for 24 hours. Solid salts that was formed was removed by filtration, and residue (filtrate) was subjected to reduced-pressure distillation by using a Vigreux column of 20 cm. The obtained product was a transparent liquid which has a boiling point of 171-175 deg C. when a pressure is 10 Pa. 1H-NMR measurement of obtained amine was performed, and it was confirmed that chemical shifts, δ (ppm), are 6.96 (d, 1H), 6.72(d, 1H), 4.07-4.04(t, 2H), 3.66-3.63 (t, 2H), 3.45-3.40 (m, 2H), 2.29(s, 3H), and 1.12-1.08(t, 3H), and 1-(2-ethoxyethyl)-2-methyl imidazole was synthesized.
Reaction SMILES: S(Cl)([Cl:3])=O.O[CH2:6][C:7]1[S:22][C:10]2[N:11]([CH2:18][CH:19]([CH3:21])[CH3:20])[C:12](=[O:17])[N:13]([CH3:16])[C:14](=[O:15])[C:9]=2[C:8]=1[S:23][CH:24]([CH3:26])[CH3:25]>ClCCl>[Cl:3][CH2:6][C:7]1[S:22][C:10]2[N:11]([CH2:18][CH:19]([CH3:21])[CH3:20])[C:12](=[O:17])[N:13]([CH3:16])[C:14](=[O:15])[C:9]=2[C:8]=1[S:23][CH:24]([CH3:26])[CH3:25]
Reactant: CC(C)Cn1c(=O)n(C)c(=O)c2c(SC(C)C)c(CO)sc21
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: CC(C)Cn1c(=O)n(C)c(=O)c2c(SC(C)C)c(CCl)sc21
Reaction time: 24 h

Procedure:
Thionyl chloride (145 μl) was added to 6-(hydroxymethyl)-3-methyl-5-[(1-methylethyl)thio]-1-(2-methylpropyl)-thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (0.45 g) in dry dichloromethane (20 ml) and the mixture was stirred for 24 hours. The solvent was evaporated to give the subtitle compound as a an oil.
Reaction SMILES: [C:1]([C:5]1[S:9][C:8]([N:10]2[CH:15]([OH:16])[CH2:14][CH2:13][N:12]([CH3:17])[C:11]2=[O:18])=[N:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][CH2:34][C:35](Cl)=[O:36])=[CH:29][CH:28]=1>C1C=CC=CC=1>[C:1]([C:5]1[S:9][C:8]([N:10]2[CH:15]([O:16][C:35](=[O:36])[CH2:34][CH2:33][C:30]3[CH:31]=[CH:32][C:27]([Cl:26])=[CH:28][CH:29]=3)[CH2:14][CH2:13][N:12]([CH3:17])[C:11]2=[O:18])=[N:7][N:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CN1CCC(O)N(c2nnc(C(C)(C)C)s2)C1=O
Reactant: O=C(Cl)CCc1ccc(Cl)cc1
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: CN1CCC(OC(=O)CCc2ccc(Cl)cc2)N(c2nnc(C(C)(C)C)s2)C1=O

Procedure:
Tetrahydro-1-(5-t-butyl-1,3,4-thiadiazol-2-yl)- 3-methyl-6-hydroxy-2(1H)-pyrimidinone (0.05 mole), triethylamine (0.06 mole) and benzene (50 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. β-(4-Chlorophenyl)propionyl chloride (0.05 mole) is then added dropwise with stirring. After the addition is completed, the reaction mixture is heated at reflux with continued stirring for a period of about 30 minutes. After this time the reaction mixture is filtered and the filtrate is stripped of solvent under reduced pressure to yield the desired product tetrahydro-1-(5-t-butyl- 1,3,4-thiadiazol-2-yl)-3-methyl-6-[β-(4-chlorophenyl)propionyloxy] -2 (1H)-pyrimidinone as the residue.
Reaction SMILES: Cl.[BH4-].[Na+].[Br:4][C:5]1[C:6]([O:26][CH3:27])=[CH:7][C:8]2[C:14]([C:15]3[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=3)=[N:13][N:12]=[C:11]([CH3:24])[CH2:10][C:9]=2[CH:25]=1>CO.O>[Br:4][C:5]1[C:6]([O:26][CH3:27])=[CH:7][C:8]2[C:14]([C:15]3[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=3)=[N:13][NH:12][CH:11]([CH3:24])[CH2:10][C:9]=2[CH:25]=1
Reactant: COc1cc2c(cc1Br)CC(C)=NN=C2c1ccc([N+](=O)[O-])cc1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COc1cc2c(cc1Br)CC(C)NN=C2c1ccc([N+](=O)[O-])cc1
Reaction time: 0.17 h

Procedure:
3.5 ml (43.2 mmol) of concentrated hydrochloric acid is first added, and then over about 10 minutes, 1.80 g (47.5 mmol) of sodium borohydride is added in portions to a suspension of 1.4 g (3.6 mmol) of 7-bromo-4-methyl-8-methoxy-1-(4-nitrophenyl)-5H-2,3-benzodiazepine (Example 3, Step C) in 60 ml of methanol. The suspension is stirred for another hour, and then diluted with water (60 ml). The crystalline material is suctioned off and washed with 50% aqueous methanol (3×50 ml). The 7-bromo-4-methyl-8-methoxy-1-(4-nitrophenyl)-4,5-dihydro-3H-2,3-benzodiazepine that is obtained as a crude product is further purified by suspension in 8 ml of hot ethanol. After suctioning-off, 1.23 g (88%) of chrome yellow crystals with a melting point of 172-174° C. is obtained.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].[NH2:11][C:12]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][C:13]=1[C:14]#[N:15].O.[OH-].[Li+]>CS(C)=O>[CH3:20][C:17]1[CH:18]=[CH:19][C:12]([NH:11][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[N+:8]([O-:10])=[O:9])=[C:13]([CH:16]=1)[C:14]#[N:15]
Reactant: Cc1ccc(N)c(C#N)c1
Reactant: O=[N+]([O-])c1ccccc1F
Agent: [Li+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: O
Product: Cc1ccc(Nc2ccccc2[N+](=O)[O-])c(C#N)c1
Temperature: 55 °C
Reaction time: 22 h
Yield: 57.1 %

Procedure:
Combine 1-fluoro-2-nitro-benzene (4.34 g, 30.79 mmol), 2-amino-5-methyl-benzonitrile (4.07 g, 30.79 mmol), lithium hydroxide monohydrate (2.58 g, 61.58 mmol) and DMSO (50.0 ml). Stir the mixture at 55° C. for 22 hours, cool to ambient temperature and pour the mixture onto ice chips and stir. After 1 hour, remove the resulting precipitate by vacuum filtration. Dry the precipitate under vacuum, purify on silica gel using dichloromethane/hexanes (75:25) to give 4.45 g (57%) of an orange solid: mp 135-139° C.; mass spectrum (ion spray): m/z=254.0 (M+1).
Reaction SMILES: C1(C)C(C)=CC=CC=1.[O:9]1[CH2:13][CH2:12][O:11][CH:10]1[CH2:14][N:15]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([O:25][CH3:26])[CH:23]=2)[C:18]([CH3:27])=[CH:17][C:16]1=[O:28].C([O:31]CC)C>>[O:9]1[CH2:13][CH2:12][O:11][CH:10]1[CH2:14][N:15]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([O:25][CH3:26])[CH:23]=2)[C:18]([CH:27]=[O:31])=[CH:17][C:16]1=[O:28]
Reactant: CCOCC
Reactant: COc1ccc2c(C)cc(=O)n(CC3OCCO3)c2c1
Solvent: Cc1ccccc1C
Product: COc1ccc2c(C=O)cc(=O)n(CC3OCCO3)c2c1
Temperature: 60 °C
Reaction time: 6 h

Procedure:
To 3 mL of a xylene solution containing 50 mg of 1-(1,3-dioxolan-2-ylmethyl)-7-methoxy-4-methylquinolin-2(1H)-one, 20 mg of serene dioxide was added, and the mixture was stirred for 6 hours under reflux. The reaction mixture was cooled to 60° C., the insoluble material filtered off, and the filtration residue was washed with chloroform. The filtrate and the washing solution were combined, and the solvent was removed under reduced pressure. The residue thus obtained was added with diethyl ether, and a solid substance was collected by filtration to obtain a yellow solid, 34 mg of 1-(1,3-dioxolan-2-ylmethyl)-7-methoxy-2-oxo-1,2-dihydroquinoline-4-carbaldehyde.
Reaction SMILES: [CH:1]([C:4]1[C:5](=[O:20])[NH:6][C:7](=[O:19])[NH:8][C:9]=1[O:10][C:11]1[CH:16]=[C:15]([CH3:17])[CH:14]=[C:13]([CH3:18])[CH:12]=1)([CH3:3])[CH3:2].[CH3:21][C:22]1[CH:23]=[C:24]([CH:27]=[C:28]([CH3:30])[CH:29]=1)[CH2:25]Br>>[CH3:21][C:22]1[CH:29]=[C:28]([CH:27]=[C:24]([CH3:25])[CH:23]=1)[CH2:30][N:8]1[C:9]([O:10][C:11]2[CH:12]=[C:13]([CH3:18])[CH:14]=[C:15]([CH3:17])[CH:16]=2)=[C:4]([CH:1]([CH3:3])[CH3:2])[C:5](=[O:20])[NH:6][C:7]1=[O:19]
Reactant: Cc1cc(C)cc(Oc2[nH]c(=O)[nH]c(=O)c2C(C)C)c1
Reactant: Cc1cc(C)cc(CBr)c1
Product: Cc1cc(C)cc(Cn2c(Oc3cc(C)cc(C)c3)c(C(C)C)c(=O)[nH]c2=O)c1
Yield: 66.2 %

Procedure:
5-Isopropyl-6-(3,5-dimethylphenoxy)-2,4-pyrimidinedione and 3,5-dimethylbenzyl bromide were reacted by the same way with the example 1 to obtain the titled compound (260 mg, yield: 66.2%).
Reaction SMILES: [CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[CH:11]=2)[C:6](=[O:19])[C:5]([C:20]([O:22]CC)=[O:21])=[CH:4]1)[CH3:2].[OH-].[K+]>C(O)(=O)C>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([N:13]3[CH2:14][CH2:15][NH:16][CH2:17][CH2:18]3)[CH:11]=2)[C:6](=[O:19])[C:5]([C:20]([OH:22])=[O:21])=[CH:4]1)[CH3:2]
Reactant: CCOC(=O)c1cn(CC)c2cc(N3CCNCC3)ccc2c1=O
Agent: [K+]
Agent: [OH-]
Solvent: CC(=O)O
Product: CCn1cc(C(=O)O)c(=O)c2ccc(N3CCNCC3)cc21
Temperature: 90 °C
Yield: 101.1 %

Procedure:
To 2.0 g of ethyl 1,4-dihydro-1-ethyl-4-oxo-7-(1-piperazinyl)quinoline-3-carboxylate was added 10 ml of a 5% aqueous solution of potassium hydroxide. The mixture was heated at 90° C for 30 minutes with stirring and neutralized, under cooling, with acetic acid to separate out a solid which was collected, and recrystallized from a mixture of ethanol and water to give 1.85 g of the product, m.p. 272° - 275° C.
Reaction SMILES: [C:1]1([C:7]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[N:11][C:10]([NH:19][CH3:20])=[CH:9][N+:8]=2[O-:21])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:22]([O:26][C:27](=[O:35])[CH2:28][O:29][CH2:30][CH2:31][CH2:32][CH2:33]Br)([CH3:25])([CH3:24])[CH3:23]>>[C:1]1([C:7]2[C:12]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[N:11][C:10]([N:19]([CH2:33][CH2:32][CH2:31][CH2:30][O:29][CH2:28][C:27]([O:26][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:35])[CH3:20])=[CH:9][N+:8]=2[O-:21])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)(C)OC(=O)COCCCCBr
Reactant: CNc1c[n+]([O-])c(-c2ccccc2)c(-c2ccccc2)n1
Product: CN(CCCCOCC(=O)OC(C)(C)C)c1c[n+]([O-])c(-c2ccccc2)c(-c2ccccc2)n1

Procedure:
In the same manner as in Example 22, except that 2,3-diphenyl-5-(methylamino)pyrazine 1-oxide was used in place of 5,6-diphenyl-2-(methylamino)pyrazine and 2-(4-bromobutyloxy)acetic acid tert-butyl ester was used in place of 2-(4-bromobutyloxy)acetic acid methyl ester, the desired compound was prepared as a pale yellow oily substance.
Reaction SMILES: C([O:8][C:9]([C:11]1[O:36][C:14]2=[CH:15][CH:16]=[C:17]3[C:21]([N:20]([CH2:22][C@@H:23]([NH:25][C:26]([O:28][CH2:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[O:27])[CH3:24])[N:19]=[CH:18]3)=[C:13]2[CH:12]=1)=[O:10])C1C=CC=CC=1.[OH-].[Li+]>C(O)C.O>[CH2:29]([O:28][C:26]([NH:25][C@@H:23]([CH3:24])[CH2:22][N:20]1[C:21]2[C:17](=[CH:16][CH:15]=[C:14]3[O:36][C:11]([C:9]([OH:10])=[O:8])=[CH:12][C:13]3=2)[CH:18]=[N:19]1)=[O:27])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: C[C@@H](Cn1ncc2ccc3oc(C(=O)OCc4ccccc4)cc3c21)NC(=O)OCc1ccccc1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: C[C@@H](Cn1ncc2ccc3oc(C(=O)O)cc3c21)NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 98.4 %

Procedure:
To a solution of the product of Step A, Example 2 (0.15 g, 0.31 mmol) in ethanol (10 mL) was added lithium hydroxide (0.026 g, 0.62 mmol) in water (1 mL) and stirred at room temperature for 16 h. The reaction mixture was evaporated to a residue and a saturated aqueous solution of ammonium chloride (20 mL) was added followed by the addition of phosphoric acid (1 M) until the solution was neutral. The mixture was extracted with ethyl acetate (3×50 mL) and the combined extracts were washed with brine (30 mL), dried and evaporated. The residue was purified by chromatography (silica, dichloromethane, 5% methanol in dichloromethane, 10% methanol in dichloromethane) to give an oil (0.12 g, 98%): MS (ES) m/z 394 (M+); 1H NMR (CD3OD) δ 7.91 (s, 1H), 7.81 (s, 1H), 7.58 (d, 1H, J=8.8 Hz), 7.25 (d, 1H, J=8.8 Hz), 7.14-7.02 (m, 5H), 4.81 (s, 2H), 4.49-4.42 (m, 2H), 4.17 (m, 1H), 1.18 (d, 3H, J=6.8 Hz).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=O.[CH2:17]([CH:19]([CH2:25][CH3:26])[C:20](=O)[CH2:21][C:22]#[N:23])[CH3:18].CS(O)(=O)=O>C1(C)C=CC=CC=1>[Cl:8][C:5]1[CH:4]=[C:3]2[C:2](=[CH:7][CH:6]=1)[N:1]=[C:20]([CH:19]([CH2:25][CH3:26])[CH2:17][CH3:18])[C:21]([C:22]#[N:23])=[C:9]2[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: Nc1ccc(Cl)cc1C(=O)c1ccccc1
Reactant: CCC(CC)C(=O)CC#N
Agent: CS(=O)(=O)O
Solvent: Cc1ccccc1
Product: CCC(CC)c1nc2ccc(Cl)cc2c(-c2ccccc2)c1C#N
Temperature: 25 °C
Yield: 45.6 %

Procedure:
A solution of (2-amino-5-chlorophenyl)(phenyl)methanone (700 mg, 3.02 mmol), 4-ethyl-3-oxo-hexanenitrile (505 mg, 3.63 mmol) and methanesulfonic acid (290 mg, 196 μl, 3.02 mmol) in toluene (40 ml) was stirred for 5 min at room temperature and then heated to reflux using a Dean-Stark-trap to remove water. After 2.5 h the mixture was cooled to room temperature, washed with saturated NaHCO3 solution and water and was evaporated. n-Heptane was added to the remaining residue and the off-white precipitate that formed was filtered off. The precipitate was again dissolved in EtOAc and the solution was washed with saturated NaHCO3 solution and water and was evaporated to yield the title compound (461 mg, 46%) as yellow solid. The filtrate was concentrated and the remaining residue was purified by column chromatography (silica gel, heptane/EtOAc 100:0-0:100) to afford a second batch of the title compound (347 mg, 34%) as yellow solid. MS (ESI): 335.1 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][CH2:13][CH2:14][CH2:15]I)[CH:7]=[C:6]2[CH:17]=[O:18].N(C1(C#N)CCCCC1)=NC1(C#N)CCCCC1.C([SnH](CCCC)CCCC)CCC.[F-].[K+]>C1(C)C=CC=CC=1.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]1[CH2:12][CH2:13][CH2:14][CH2:15][C:7]1=[C:6]2[CH:17]=[O:18]
Reactant: COc1ccc2c(c1)c(C=O)cn2CCCCI
Agent: CCCC[SnH](CCCC)CCCC
Agent: N#CC1(N=NC2(C#N)CCCCC2)CCCCC1
Agent: [F-]
Solvent: O
Solvent: Cc1ccccc1
Product: COc1ccc2c(c1)c(C=O)c1n2CCCC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a stirred solution of 5-methoxy-1-(4-iodobutyl)indole-3-carboxaldehyde in toluene at reflux under argon is added dropwise over 2 h a solution of 1,1′-azobis(cyclohexanecarbonitrile) and tri-n-butyltin hydride in toluene. The mixture is stirred for 3 h, cooled to room temperature, and potassium fluoride and water are added. The mixture is stirred for 18 h and filtered through a pad of kieselguhr. The filter-cake is washed (ethyl acetate) and the filtrate is concentrated in vacuo and purified by column chromatography to give the product.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][CH:29]=1)[CH2:5][N:6]1[C:18]2[CH2:17][CH2:16][CH:15]([NH:19][C:20]([CH:22]3[CH2:24][CH2:23]3)=[O:21])[CH2:14][C:13]=2[C:12]2[C:7]1=[CH:8][CH:9]=[C:10]([CH:25]=O)[CH:11]=2.[O:30]([NH2:32])[CH3:31].[OH-].[Na+]>CCO.O>[F:1][C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][CH:29]=1)[CH2:5][N:6]1[C:18]2[CH2:17][CH2:16][CH:15]([NH:19][C:20]([CH:22]3[CH2:24][CH2:23]3)=[O:21])[CH2:14][C:13]=2[C:12]2[C:7]1=[CH:8][CH:9]=[C:10]([CH:25]=[N:32][O:30][CH3:31])[CH:11]=2
Reactant: O=Cc1ccc2c(c1)c1c(n2Cc2cccc(F)c2)CCC(NC(=O)C2CC2)C1
Reactant: CON
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CON=Cc1ccc2c(c1)c1c(n2Cc2cccc(F)c2)CCC(NC(=O)C2CC2)C1
Reaction time: 18 h
Yield: 61 %

Procedure:
Combine cyclopropanecarboxylic acid[9-(3-fluoro-benzyl)-6-formyl-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-amide (Preparation 70) (0.32 g, 0.82 mmol), methoxylamine (0.21 g, 2.4 mmol), and sodium hydroxide (0.049 g, 1.3 mmol) in EtOH (15 mL). Add enough water to dissolve the sodium hydroxide and stir for 18 h. Dilute with water and extract with EtOAc. Dry EtOAc extracts over Na2SO4 and filter twice through a pad of silica to give 0.21 g (61%) of an off-white solid. MS (ES): m/z 420 (M+1).
Reaction SMILES: [CH2:1]1[C:6]2[NH:7][C:8]3[C:13]([C:14](=[O:15])[C:5]=2[CH2:4][C:3]2[NH:16][C:17]4[C:22]([C:23](=[O:24])[C:2]1=2)=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:12][CH:11]=[CH:10][CH:9]=3.[OH-].[Na+].[Na+].[Na+].C1C2C(=O)C3C(=CC=C(S([O-])(=O)=O)C=3)C(=O)C=2C=CC=1S([O-])(=O)=O.OO>O.CO>[CH:20]1[CH:21]=[C:22]2[C:23]([C:2]3[C:3]([NH:16][C:17]2=[CH:18][CH:19]=1)=[CH:4][C:5]1[C:14]([C:13]2[C:8]([NH:7][C:6]=1[CH:1]=3)=[CH:9][CH:10]=[CH:11][CH:12]=2)=[O:15])=[O:24]
Reactant: O=c1c2c([nH]c3ccccc13)Cc1c([nH]c3ccccc3c1=O)C2
Agent: O=C1c2ccc(S(=O)(=O)[O-])cc2C(=O)c2cc(S(=O)(=O)[O-])ccc21
Agent: OO
Agent: [Na+]
Solvent: O
Solvent: CO
Product: O=c1c2ccccc2[nH]c2cc3c(=O)c4ccccc4[nH]c3cc12
Temperature: 23.5 °C
Reaction time: 0.17 h

Procedure:
A one liter flask equipped with a thermometer, stirrer and condenser is charged with 50 G 6,13-dihydroquinacridone, 200 ml methanol, 1 g polyvinyl pyrrolidone powder (Luviskol® K-30, BASF) and 7 g of the aqueous presscake of the nanosize quinacridone naphthalene sulfonic acid formaldehyde polymer mixture according to Example 2, are stirred at 20-27° C. for 10 minutes. 73 g 50% aqueous sodium hydroxide are added. The mixture is stirred under a slow flow of nitrogen at 50-53° C. for 30 minutes. 4.6 g of a 37% aqueous solution of anthraquinone-2,7-disulfonic acid disodium salt is added as catalyst followed by 10 ml water and the reaction mixture is heated to reflux for 40 minutes. 79 g of an aqueous 18.2% hydrogen peroxide solution are added into the reaction mixture with a peristaltic pump at a pumping rate of 0.4 ml/minute. Then after 20 minutes addition time 2.3 g phthalimido methyl-quinacridone and after another 70 minutes 0.3 g phthalimido methyl-quinacridone are introduced into the reaction mixture followed by continuing the hydrogen peroxide addition while maintaining reflux and a slow nitrogen flow. The resulting violet suspension is further stirred for 10 minutes at reflux then diluted with 100 ml cold water and filtered. The presscake is washed with hot water then dried, yielding a violet quinacridone.