Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH:5]=[CH:6][C:7]=1[N+:8]([O-])=O.[C:16]1([CH3:25])[C:17]([N:22]=[C:23]=S)=[CH:18][CH:19]=[CH:20][CH:21]=1>C(O)C.[Pd]>[CH3:25][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[NH:22][C:23]1[O:1][C:2]2[CH:3]=[C:4]([CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH:5]=[CH:6][C:7]=2[N:8]=1
Reactant: Cc1ccccc1N=C=S
Reactant: COC(=O)Cc1ccc([N+](=O)[O-])c(O)c1
Agent: [Pd]
Solvent: CCO
Product: COC(=O)Cc1ccc2nc(Nc3ccccc3C)oc2c1
Temperature: 25 °C
Reaction time: 15 h
Yield: 84 %

Procedure:
In ethanol (20 ml) was dissolved methyl 3-hydroxy-4-nitrophenylacetate (1.00 g, 4.74 mmol), followed by the addition of 5% palladium/carbon (500 mg). Under stirring at room temperature, the mixture was subjected to catalytic hydrogenation for 15 hours. After filtration of the reaction mixture through Celite to remove the insoluble matter, 2-tolyl isothiocyanate (765 μl, 5.69 mmol) was added to the filtrate while stirring at room temperature. The reaction mixture was stirred for 15 hours. After addition of mercuric oxide (yellow) (1.72 g, 7.94 mmol), the mixture was heated under reflux for 5 hours under stirring. The reaction mixture was then cooled to room temperature. After filtration of the reaction mixture through Celite under reduced pressure, the solvent was distilled off under reduced pressure from the filtrate. The residue was purified by chromatography on a silica gel column, whereby from chloroform-ethyl acetate (10:1) eluate fractions, the title compound (1.18 g, 84%) was obtained as a yellow oil.
Reaction SMILES: [CH3:1][NH:2][CH3:3].[C:4]([O:8][CH2:9][CH3:10])(=[O:7])[CH:5]=[CH2:6].C1C2NC3C(=CC=CC=3)SC=2C=CC=1.COC1C=CC(O)=CC=1>>[CH3:1][N:2]([CH2:6][CH2:5][C:4]([O:8][CH2:9][CH3:10])=[O:7])[CH3:3]
Reactant: CNC
Reactant: C=CC(=O)OCC
Agent: COc1ccc(O)cc1
Agent: c1ccc2c(c1)Nc1ccccc1S2
Product: CCOC(=O)CCN(C)C
Temperature: -13 °C

Procedure:
To a chilled (-15° C.) reaction vessel there was added; anhydrous dimethylamine (100 grams); ethyl acrylate (250 grams); phenothiazine (0.5 gram); and p-methoxyphenol (0.5 gram). The mixture was maintained at -13° C. for 2 hours with stirring after which the temperature was allowed to rise to about 25° C. Unreacted dimethylamine and ethyl acrylate were removed by distillation. The product was recovered by distillation at 58° C. and 10 mm. mercury pressure in a yield of 97 per cent. The product, designated herein as Amine Catalyst VIII, has the formula, (CH3)2NCH2CH2C(O)OC2H5, as verified analytically by infrared spectroscopy.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[CH3:9][C:10]1[O:11][C:12]2[CH:18]=[CH:17][C:16](N)=[CH:15][C:13]=2[N:14]=1.CC[N:22](CC)CC>CCO>[Cl:1][C:2]1[N:7]=[C:6]([NH:22][C:17]2[CH:16]=[CH:15][C:13]3[N:14]=[C:10]([CH3:9])[O:11][C:12]=3[CH:18]=2)[CH:5]=[CH:4][N:3]=1
Reactant: CCN(CC)CC
Reactant: Cc1nc2cc(N)ccc2o1
Reactant: Clc1ccnc(Cl)n1
Solvent: CCO
Product: Cc1nc2ccc(Nc3ccnc(Cl)n3)cc2o1
Yield: 73 %

Procedure:
To a solution of 2,4-dichloropyrimidine (1 mmol) and 2-methyl-1,3-benzoxazol-5-amine (1 mmol) in 5 ml EtOH was added Et3N (1 mmol). The reaction mixture was refluxed for 5 h. After removal of the solvent in vacuo and addition of H2O, the mixture was extracted with EtOAc. The organic layers were combined, washed with a saturated NaCl aqueous solution, dried over anhydrous Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography to give N-(2-chloro pyrimidin-4-yl)-2-methylbenzo[d]oxazol-6-amine in a yield of 73%.
Reaction SMILES: [CH2:1]([CH:3]1[NH:8][CH:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]([NH2:15])[CH2:5][CH2:4]1)[CH3:2].[C:16]([C:24]([C:39]([OH:41])=[O:40])([OH:38])[C:25]([C:30](=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)([OH:29])[C:26]([OH:28])=[O:27])(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CC(O)C.O>[C:30]([C@@:25]([C:26]([OH:28])=[O:27])([OH:29])[C@@:24]([C:16](=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([OH:38])[C:39]([OH:41])=[O:40])(=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.[CH2:1]([C@@H:3]1[NH:8][C@@H:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C@@H:6]([NH2:15])[CH2:5][CH2:4]1)[CH3:2]
Reactant: CCC1CCC(N)C(c2ccccc2)N1
Reactant: O=C(O)C(O)(C(=O)c1ccccc1)C(O)(C(=O)O)C(=O)c1ccccc1
Solvent: CC(C)O
Solvent: O
Product: CC[C@H]1CC[C@H](N)[C@H](c2ccccc2)N1
Product: O=C(O)[C@@](O)(C(=O)c1ccccc1)[C@@](O)(C(=O)O)C(=O)c1ccccc1

Procedure:
(+/−)-6-Ethyl-2-phenyl-piperidin-3-ylamine (102 mg, 0.50 mmol) and (−) dibenzoyltartaric acid were dissolved by heating in 5 mL 2-propanol and 1 mL water. The resultant solid (26 mg, 25%) was determined to be 94% enriched in the (2S,3S,6S)-enantiomer.
Reaction SMILES: C([N:8]1[CH2:14][CH2:13][C:12]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[O:11][CH2:10][CH2:9]1)C1C=CC=CC=1.Cl[C:28]([O:30][CH2:31][CH3:32])=[O:29]>C(Cl)Cl>[C:28]([N:8]1[CH2:14][CH2:13][C:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:11][CH2:10][CH2:9]1)([O:30][CH2:31][CH3:32])=[O:29]
Reactant: c1ccc(CN2CCOC(c3ccccc3)(c3ccccc3)CC2)cc1
Reactant: CCOC(=O)Cl
Solvent: ClCCl
Product: CCOC(=O)N1CCOC(c2ccccc2)(c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To the solution of 30.25 g of 4-benzyl-7,7-diphenyl-hexahydro-1,4-oxazepine in 300 ml of methylene chloride, that of 10.4 g of ethyl chloroformate in 100 ml of methylene chloride is added dropwise while stirring. After 30 minutes the mixture is allowed to warm up to room temperature and stirred for 15 hours. It is successively washed twice with 50 ml of N hydrochloric acid, 50 ml of N aqueous sodium hydroxide and 50 ml of saturated sodium chloride each, dried, filtered and evaporated. The residue is recrystallized from hexane, to yield the 4-carbethoxy-7,7-diphenyl-hexahydro-1,4-oxazepine melting at 122° to 123°.
Reaction SMILES: I[C:2]1[CH:18]=[CH:17][C:5]2[N:6]([CH2:10][CH2:11][N:12]3[CH2:16][CH2:15][CH2:14][CH2:13]3)[C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1.[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]2[CH:27]=[CH:28][C:29]([C:32]#[CH:33])=[N:30][CH:31]=2)=[CH:22][CH:21]=1>>[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([C:26]2[CH:27]=[CH:28][C:29]([C:32]#[C:33][C:2]3[CH:18]=[CH:17][C:5]4[N:6]([CH2:10][CH2:11][N:12]5[CH2:16][CH2:15][CH2:14][CH2:13]5)[C:7](=[O:9])[NH:8][C:4]=4[CH:3]=3)=[N:30][CH:31]=2)=[CH:24][CH:25]=1
Reactant: O=c1[nH]c2cc(I)ccc2n1CCN1CCCC1
Reactant: C#Cc1ccc(-c2ccc(Cl)cc2)cn1
Product: O=c1[nH]c2cc(C#Cc3ccc(-c4ccc(Cl)cc4)cn3)ccc2n1CCN1CCCC1

Procedure:
Prepared according to general working method II from 5-iodo-1-(2-pyrrolidin-1-yl-ethyl)-1,3-dihydro-benzimidazol-2-one (140 mg, 0.39 mmol) and 5-(4-chloro-phenyl)-2-ethynyl-pyridine (83 mg, 0.39 mmol).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][NH:16][C:17]2[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][C:25]([O:27]C)=[O:26])=[CH:19][CH:18]=2)[CH:10]=1.[OH-].[Na+].O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO.O1CCCC1>[CH3:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][NH:16][C:17]2[CH:18]=[CH:19][C:20]([CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[CH:21][CH:22]=2)[CH:10]=1
Reactant: COC(=O)CCc1ccc(NCc2cccc(-c3c(C)cccc3C)c2)cc1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: Cc1cccc(C)c1-c1cccc(CNc2ccc(CCC(=O)O)cc2)c1
Temperature: 25 °C
Reaction time: 21 h
Yield: 56.9 %

Procedure:
To a solution of methyl 3-(4-{[(2′,6′-dimethylbiphenyl-3-yl)methyl]amino}phenyl)propanoate (0.486 g, 1.30 mmol) in a mixture of methanol (6 mL) and tetrahydrofuran (6 mL) was added 2 M aqueous sodium hydroxide solution (2 mL), and the mixture was stirred at room temperature for 21 hr. Water was added to the reaction mixture, and the mixture was weakly acidified with 10% aqueous citric acid 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 silica gel column chromatography (30% ethyl acetate/hexane-ethyl acetate) and recrystallized from ethyl acetate-hexane to give the title compound (0.266 g, yield 57%) as colorless needle crystals.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([C:17]([O:19]C)=[O:18])=[C:9]1[CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>O1CCCC1.CO.O>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([C:17]([OH:19])=[O:18])=[C:9]1[CH3:21])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)c1c(C)n(Cc2ccccc2)c2ccccc12
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Solvent: CO
Product: Cc1c(C(=O)O)c2ccccc2n1Cc1ccccc1
Temperature: 60 °C
Reaction time: 12 h
Yield: 49.9 %

Procedure:
To a solution of methyl 1-benzyl-2-methyl-1H-indole-3-carboxylate (446 mg, 1.6 mmol) in tetrahydrofuran (20 mL) and methanol (7 mL) was added sodium hydroxide (320 mg, 8 mmol) in water (7 mL), then stirred at 60° C. for 12 hours. The reaction mixture was concentrated in vacuo and acidified to PH=4 with 6 N hydrochloric acid, collected and dried to give 1-benzyl-2-methyl-1H-indole-3-carboxylic acid as a white solid (212 mg, 50%). LRMS (M+H+) m/z: calcd 265.11. found 265.
Reaction SMILES: [CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@@H:11]3[CH2:19][N:14]4[CH2:15][CH2:16][NH:17][CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.[F:20][C:21]([F:33])([F:32])[C:22]1[CH:23]=[C:24]([S:28](Cl)(=[O:30])=[O:29])[CH:25]=[CH:26][CH:27]=1.C(N(CC)CC)C>ClCCl>[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@@H:11]3[CH2:19][N:14]4[CH2:15][CH2:16][N:17]([S:28]([C:24]5[CH:25]=[CH:26][CH:27]=[C:22]([C:21]([F:20])([F:32])[F:33])[CH:23]=5)(=[O:30])=[O:29])[CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1
Reactant: O=S(=O)(Cl)c1cccc(C(F)(F)F)c1
Reactant: c1nc(C2CC2)cnc1O[C@H]1C[C@H]2CNCCN2C1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=S(=O)(c1cccc(C(F)(F)F)c1)N1CCN2C[C@@H](Oc3cnc(C4CC4)cn3)C[C@H]2C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of Example 49B (200 mg, 0.674 mmol)) in dichloromethane (3 mL) was added 3-(trifluoromethyl)benzene-1-sulfonyl chloride (198 mg, 0.809 mmol) followed by triethylamine (0.3 mL). The mixture was stirred at room temperature overnight and then concentrated. The residue was purified by flash chromatography (ethyl acetate/hexane=1:1) to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.80 (m, 2H), 0.92 (m, 2H), 1.38 (m, 1H), 2.04-2.20 (m, 4H), 2.42 (m, 3H), 3.00 (m, 2H), 3.66 (m, 1H), 3.82 (m, 1H), 5.20 (m, 1H), 7.92 (m, 1H), 7.98 (m, 1H), 8.03 (m, 1H), 8.11 (m, 3H); MS (ESI) m/z 469 (M+H)+.
Reaction SMILES: [H-].[Na+].[CH2:3]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]([OH:18])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4]1.Cl[CH2:20][C:21]([N:23]([CH3:25])[CH3:24])=[O:22]>CCCCCC.CCOCC>[CH:16]1[C:17]2[CH2:3][CH2:4][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:10]=3[CH:11]([O:18][CH2:20][C:21]([N:23]([CH3:25])[CH3:24])=[O:22])[C:12]=2[CH:13]=[CH:14][CH:15]=1
Reactant: OC1c2ccccc2CCc2ccccc21
Reactant: CN(C)C(=O)CCl
Agent: [H-]
Agent: [Na+]
Solvent: CCCCCC
Solvent: CCOCC
Product: CN(C)C(=O)COC1c2ccccc2CCc2ccccc21
Temperature: 25 °C
Reaction time: 16 h
Yield: 72.3 %

Procedure:
Washed sodium hydride (2.6 g, 64.6 mmol, 60 weight % in oil) two times with hexane under a nitrogen atmosphere. Added 50 mL of dry ether, and then added dibenzosuberol (13.6 g, 64.6 mmol) dissolved in 30 mL of dry ether followed by 2-chloro-N,N-dimethylacetamide (7.8 g, 64.6 mmol) dissolved in 20 mL of dry ether. Stirred at room temperature for 16 hours. Added water, and separated layers. Evaporated the organic solution, and triturated the residue with carbon tetrachloride and hexane. Filtered the white solid to give 13.79 g (72% yield) of 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl-oxy-N,N-dimethylacetamide.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([C:9]([S:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[N+:30]([O-:32])=[O:31])=[CH:10][N:11]2[CH2:14][C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([F:22])[CH:16]=2)=[CH:7][CH:6]=1)=[O:4].O[Li].O.Cl>O1CCOCC1.O>[F:22][C:17]1[CH:16]=[C:15]([CH:20]=[C:19]([F:21])[CH:18]=1)[CH2:14][N:11]1[C:12]2[C:8](=[CH:7][CH:6]=[C:5]([C:3]([OH:4])=[O:2])[CH:13]=2)[C:9]([S:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[N+:30]([O-:32])=[O:31])=[CH:10]1
Reactant: COC(=O)c1ccc2c(Sc3ccccc3[N+](=O)[O-])cn(Cc3cc(F)cc(F)c3)c2c1
Agent: Cl
Agent: [Li]O
Solvent: O
Solvent: C1COCCO1
Product: O=C(O)c1ccc2c(Sc3ccccc3[N+](=O)[O-])cn(Cc3cc(F)cc(F)c3)c2c1
Temperature: 60 °C
Reaction time: 8 h
Yield: 89 %

Procedure:
To a solution of 1-(3,5-Difluoro-benzyl)-3-(2-nitro-phenylsulfanyl)-1H-indole-6-carboxylic acid methyl ester (150.0 mg, 0.33 mmol) in dioxane (20 mL) and water (15 mL) was added LiOH.H2O (83.1 mg, 2.0 mmol) in 5 ml water. The reaction mixture was stirred overnight at 60° C. The mixture was then acidified to pH 4 by addition of 15% aqueous HCl and the mixture was extracted twice with ethyl acetate. The combined organic layers were dried over Na2SO4 and concentrated in vacuo to give a yellow powder. The product was recrystallised from heptane/ethyl acetate to give the title compound as yellow/orange crystals (129.3 mg, y=89%)
Reaction SMILES: [Br-:1].[Br-].[Br-].C([N+](C)(C)C)C1C=CC=CC=1.C([N+](C)(C)C)C1C=CC=CC=1.C([N+](C)(C)C)C1C=CC=CC=1.[CH3:37][C:38]1[CH:39]=[C:40]([NH:45][C:46](=[O:48])[CH3:47])[CH:41]=[C:42]([CH3:44])[CH:43]=1>C(Cl)Cl.CO>[Br:1][C:43]1[C:42]([CH3:44])=[CH:41][C:40]([NH:45][C:46](=[O:48])[CH3:47])=[CH:39][C:38]=1[CH3:37]
Reactant: [Br-]
Reactant: CC(=O)Nc1cc(C)cc(C)c1
Agent: C[N+](C)(C)Cc1ccccc1
Solvent: ClCCl
Solvent: CO
Product: CC(=O)Nc1cc(C)c(Br)c(C)c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 89.9 %

Procedure:
Benzyltrimethylammonium tribromide (BTMA-Br3) (7.8 g, 20.21 mmol) was added to a solution of N-(3,5-dimethyl-phenyl)-acetamide (3.0 g, 18.38 mmol) in CH2Cl2/MeOH (90 ml/90 ml) at room temperature in an Ar atmosphere. The reaction mixture was stirred at room temperature for 10 minutes. The reaction mixture was concentrated under reduced pressure, and CH2Cl2 was then added to the resulting residue. The organic layer was washed with H2O, and then dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:EtOAc=1:1) to give N-(4-bromo-3,5-dimethyl-phenyl)-acetamide (4.0 g, yield 90%).
Reaction SMILES: Br[CH2:2][C:3]1[CH:10]=[CH:9][C:6]([CH:7]=[O:8])=[CH:5][C:4]=1[Cl:11].C([O-])([O-])=O.[K+].[K+].[NH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1>CN(C)C(=O)C.O>[Cl:11][C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:3]=1[CH2:2][NH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1)[CH:7]=[O:8]
Reactant: Nc1ccccn1
Reactant: O=Cc1ccc(CBr)c(Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: O=Cc1ccc(CNc2ccccn2)c(Cl)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 49.6 %

Procedure:
To a stirred solution of 4-(bromomethyl)-3-chlorobenzaldehyde (2 g, 9 mmol) in N,N-dimethylacetamide (DMA; 20 mL) was added K2CO3 (2.36 g, 17.16 mmol) and 2-aminopyridine (0.84 g, 8.58 mmol), and the reaction mixture was stirred at ambient temperature for 4 h. The reaction mixture was diluted with H2O and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by flash column chromatography (SiO2, 100-200 mesh; 20% EtOAc in n-Hexane) to afford the title compound as off-white solid (1.05 g, 50%): mp 122-123° C.; 1H NMR (400 MHz, CDCl3) δ 9.94 (s, 1H), 8.11 (s, 1H), 7.88 (s, 1H), 7.72 (d, J=4.8 Hz, 1H), 7.62 (d, J=5.7 Hz, 1H), 7.4 (m, 1H), 6.64 (d, J=3.9 Hz, 1H), 6.38 (d, J=6.3 Hz, 1H), 5.04 (br s, 1H), 4.71 (s, 2H); ESIMS m/z 246.97 ([M+H]+).
Reaction SMILES: [C:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH3:14])[CH:11]=2)[CH2:6][C:5]1=[O:15])(=[O:3])[CH3:2].[CH3:16][CH2:17][O:18][C:19](OCC)(OCC)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(OC(=O)C)(=O)C>>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH3:14])[CH:11]=2)[C:6](=[C:19]([O:18][CH2:17][CH3:16])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:5]1=[O:15])(=[O:3])[CH3:2]
Reactant: CCOC(OCC)(OCC)c1ccccc1
Reactant: COc1ccc2c(c1)N(C(C)=O)C(=O)C2
Solvent: CC(=O)OC(C)=O
Product: CCOC(=C1C(=O)N(C(C)=O)c2cc(OC)ccc21)c1ccccc1

Procedure:
Prepared from 1-acetyl-6-methoxy-2-indolinone, triethyl orthobenzoate and acetic anhydride
Reaction SMILES: [CH3:1][S:2]([CH2:5][C:6](=O)[CH3:7])(=[O:4])=[O:3].O.[NH2:10][NH2:11]>C(O)C>[CH3:1][S:2]([CH2:5][C:6](=[N:10][NH2:11])[CH3:7])(=[O:4])=[O:3]
Reactant: CC(=O)CS(C)(=O)=O
Reactant: NN
Solvent: CCO
Solvent: O
Product: CC(CS(C)(=O)=O)=NN
Temperature: 0 °C
Reaction time: 23.5 h

Procedure:
To a 200 ml volume four-necked flask, 1-methylsulfonyl-2-propanone (7-2-1) (10.21 g) and ethanol (50 ml) were added under a nitrogen atmosphere and cooled to 0° C. Hydrazine monohydrate (14-b) (3.9 ml) was added dropwise. After stirring at room temperature for 23.5 hours, the mixture was concentrated under reduced pressure to give 10.69 g of (1-methylsulfonyl-2-propylidene)hydrazine (5-2-2).
Reaction SMILES: Cl[Si:2]([CH3:20])([CH3:19])[CH:3]1[C:11]2[C:6](=[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]1[CH3:18].[CH3:21][C:22]1[CH-:26][C:25]([CH3:27])=[C:24]([CH3:28])[C:23]=1[CH3:29].[Na+]>O1CCCC1>[CH3:19][Si:2]([CH3:20])([CH:3]1[C:11]2[C:6](=[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]1[CH3:18])[CH:26]1[C:25]([CH3:27])=[C:24]([CH3:28])[C:23]([CH3:29])=[C:22]1[CH3:21]
Reactant: Cc1[cH-]c(C)c(C)c1C
Reactant: CC1=Cc2c(-c3ccccc3)cccc2C1[Si](C)(C)Cl
Agent: [Na+]
Solvent: C1CCOC1
Product: CC1=Cc2c(-c3ccccc3)cccc2C1[Si](C)(C)C1C(C)=C(C)C(C)=C1C
Temperature: 25 °C
Reaction time: 23 h

Procedure:
To a light yellow solution of chlorodimethyl(2-methyl-4-phenyl-1H-indenyl)silane (9.40 g, 31.4 mmol, 1.00 eq.) in tetrahydrofuran (40 ml) at −30° C. was added sodium (tetramethylcyclopentadienide) (4.76 g, 33.0 mmol, 1.05 equiv.) in portions to give a cloudy orange solution. The reaction was allowed to warm to room temperature and stirred for 23 hours. The mixture was evaporated under vacuum, leaving an orange residue. The residue was extracted with pentane (50 ml) and the extract was filtered to give a bright yellow solution and yellow solid. The solution was evaporated under vacuum to yield thick, orange oil. Yield 10.16 g (84%). 1H NMR(C6D6): δ7.61 (d, 2H), 7.41 (m, 1H), 7.31 (m, 4H), 7.19 (m, 1H), 6.85 (s, 1H), 3.60, (s, 1H), 3.16 (br s, 1H), 2.00 (s, 3H), 1.93 (s, 3H), 1.88 (s, 3H), 1.82 (s, 6H), −0.23 (s, 3H), −0.24 (s, 3H).
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=1)#[N:2].Cl.[NH2:13][CH2:14][CH2:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C.O>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([C:7]([NH:13][CH2:14][CH2:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[O:9])=[CH:10][CH:11]=1)#[N:2]
Reactant: N#Cc1ccc(C(=O)O)cc1
Reactant: CCOC(=O)CCCN
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CCCNC(=O)c1ccc(C#N)cc1
Temperature: 25 °C
Reaction time: 14 h
Yield: 44.1 %

Procedure:
To a solution of 4-cyanobenzoic acid (2.0 g, 13.59 mmol), ethyl 4-aminobutyrate hydrochloride (2.507 g, 14.95 mmol), HOBt (0.918 g, 6.80 mmol) and TEA (6.63 mL, 47.58 mmol) in DMF (20 mL) was added WSC (3.26 g, 16.99 mmol), and the mixture was stirred at room temperature for 14 hr. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 5 to 75% ethyl acetate/hexane) to give ethyl 4-(4-cyanobenzamido)butanoate (1.558 g, 5.99 mmol, 44.0%) as a white powder.
Reaction SMILES: [C:1]([OH:13])(=O)[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[NH2:14][C@H:15]([C:19]([NH:21][C@H:22]([C@@H:30]([OH:49])[C@H:31]([OH:48])[C@@H:32]([NH:40][C:41](=[O:47])[C@H:42]([CH:44]([CH3:46])[CH3:45])[NH2:43])[CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:20])[CH:16]([CH3:18])[CH3:17].N=[C:51]=[NH:52]>>[N:52]1[C:51]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH:10]=[CH:11][C:2]=1[C:1]([NH:14][C@H:15]([C:19]([NH:21][C@H:22]([C@@H:30]([OH:49])[C@H:31]([OH:48])[C@@H:32]([NH:40][C:41](=[O:47])[C@H:42]([CH:44]([CH3:45])[CH3:46])[NH:43][C:1]([C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1)=[O:13])[CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:20])[CH:16]([CH3:18])[CH3:17])=[O:13]
Reactant: N=C=N
Reactant: CC(C)[C@H](N)C(=O)N[C@@H](Cc1ccccc1)[C@@H](O)[C@H](O)[C@H](Cc1ccccc1)NC(=O)[C@@H](N)C(C)C
Reactant: O=C(O)c1ccc2ccccc2n1
Product: CC(C)[C@H](NC(=O)c1ccc2ccccc2n1)C(=O)N[C@@H](Cc1ccccc1)[C@@H](O)[C@H](O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)c1ccc2ccccc2n1)C(C)C

Procedure:
Quinaldic acid was coupled to the resultant compound of Example 173 using the carbodiimide coupling procedure of Example 55 to provide the desired compound.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[O:12])[O:10][C:8](=O)[C:7]2=[CH:13][CH:14]=1)([OH:3])=[O:2].[NH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21]>>[C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[O:12])[N:15]([CH2:16][CH2:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21])[C:8](=[O:10])[C:7]2=[CH:13][CH:14]=1)([OH:3])=[O:2]
Reactant: O=C(O)c1ccc2c(c1)C(=O)OC2=O
Reactant: NCCCCC(=O)O
Product: O=C(O)CCCCN1C(=O)c2ccc(C(=O)O)cc2C1=O
Yield: 99.7 %

Procedure:
4-carboxyphthalic anhydride (1.0 g, 0.0052 mol) and 5-aminopentanoic acid (0.61 g, 0.0052 mol) were refluxed as above overnight. Crystallisation of the product from EtOH yielded 1.51 g (72%) of 103 as a white solid: mp=223° C.; Rf 0.79 (A): Rf 0.92 (C): Rf 0.36 (D): IR (cm−1): 2750–3375 (OH), 3084 (C═CH), 2665 (C—H), 1767 (C═O), 1705 (bs, C═O), 1620 (C═C), 1486 (C═C), 1402 (CH2), 1382 (C—O), 1302 (C—O), 732 (C═CH); MS m/z (rel intensity) 291 (15), 290 (100).
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-:8].[K+].Cl[C:11]1[C:24]2[C:23](=[O:25])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][C:21]=3[N+]([O-])=O)[C:16](=[O:29])[C:15]=2[CH:14]=[CH:13][CH:12]=1>>[O:7]([C:11]1[C:24]2[C:23](=[O:25])[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][C:21]=3[O:8][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[C:16](=[O:29])[C:15]=2[CH:14]=[CH:13][CH:12]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: [OH-]
Reactant: O=C1c2cccc(Cl)c2C(=O)c2c1cccc2[N+](=O)[O-]
Reactant: Oc1ccccc1
Agent: [K+]
Product: O=C1c2cccc(Oc3ccccc3)c2C(=O)c2c(Oc3ccccc3)cccc21
Temperature: 100 °C
Reaction time: 6 h

Procedure:
A mixture of 21 g. phenol, 13 g. potassium hydroxide and 270 g. o-chlorotoluene was converted to a water-free slurry of potassium phenoxide by azeotropic distillation of all the water formed. After cooling back to 100° C., 28.8 g. of 1-chloro-8-nitroanthraquinone was charged and the whole heated and stirred at 130° C. for 6 hours. The product was isolated by steam distillation, filtration, washing and drying. A 37.7 g. yield (96.2% of theory) of a product identical to authentic 1,8-diphenoxyanthraquinone in a thin layer chromatogram and free of starting material was obtained.