Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Na].[CH2:2]([O:4][C:5]([CH:7]([P:9](=[O:16])([O:13][CH2:14][CH3:15])[O:10][CH2:11][CH3:12])[CH3:8])=[O:6])[CH3:3].Br[C:18]([CH3:22])([CH:20]=C)[CH3:19]>C(O)C>[CH2:2]([O:4][C:5]([CH:7]([P:9]([O:10][CH2:11][CH3:12])(=[O:16])[O:13][CH2:14][CH3:15])[CH2:8][CH:19]=[C:18]([CH3:22])[CH3:20])=[O:6])[CH3:3]
Reactant: C=CC(C)(C)Br
Reactant: CCOC(=O)C(C)P(=O)(OCC)OCC
Agent: [Na]
Solvent: CCO
Product: CCOC(=O)C(CC=C(C)C)P(=O)(OCC)OCC
Reaction time: 1 h

Procedure:
The diethyl 2-ethoxycarbonly-5-methyl-hex-4-ene-2-phosphonate used in this reaction was prepared by the following procedure. 4.8 Parts of sodium metal were dissolved in 200 parts of absolute ethanol and to this solution was added 50 parts of diethyl 1-ethoxycarbonyl-ethylphosphonate. To this stirred reaction mixture at room temperature was added 31.3 parts of 2-bromo-2-methyl-but-3-ene dropwise over 1 hour. On completion of the addition stirring was continued for 1 hour at room temperature and then for 2 hours at 60° C. After cooling, the reaction mixture was filtered free of sodium bromide and the filtrate concentrated under reduced pressure to remove ethanol. The residual oil was taken up in ether, and the ether solution washed with water and evaporated. Fractional distillation of the residue gave diethyl 1-ethoxycarbonyl-4-methyl-pent-3-ene-1-phosphonate b0.3 126°-34° C. with the following percentage composition by weight.
Reaction SMILES: F[B-](F)(F)F.[CH2:6]([N:13]1[CH2:17][CH2:16][CH2:15][C:14]1=[NH:18])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH3:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[C:21]=1[N:27]=[C:28]=[O:29]>>[CH2:6]([N:13]1[CH2:17][CH2:16][CH2:15][C:14]1=[N:18][C:28]([NH:27][C:21]1[C:20]([CH3:19])=[CH:25][CH:24]=[CH:23][C:22]=1[CH3:26])=[O:29])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: Cc1cccc(C)c1N=C=O
Reactant: N=C1CCCN1Cc1ccccc1
Agent: F[B-](F)(F)F
Product: Cc1cccc(C)c1NC(=O)N=C1CCCN1Cc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
The fluoroborate salt of 1-benzyl-2-iminopyrrolidine (6.55 g.; 0.025 mole) is converted to free base (4.36 g.; 0.025 mole) in the usual manner. After drying over K2CO3, the benzene solution is filtered through diatomaceous earth and 3.68 g. (0.025 mole) of 2,6-dimethylphenylisocyanate is added. The reaction mixture is stirred at room temperature for 1 hour and then evaporated to dryness in vacuo to give an oily residue of 1-(1-benzyl-2-pyrrolidylidene)-3-(2,6-dimethylphenyl)urea which is dissolved in ether and converted to the hydrochloride salt. Recrystallizations from methanol yields the product, 1-(1-benzyl-2-pyrrolidylidene)-3-(2,6-dimethylphenyl)urea HCl, m.p. = 185°-195° C. (dec.)
Reaction SMILES: [CH2:1]([CH:4]1[CH2:9][C:8](=[O:10])[O:7][C:5]1=O)[CH:2]=[CH2:3].[Na].[N:12]1C=C[CH:15]=[CH:14][CH:13]=1>C(OCC)C>[CH2:13]([N:12]1[C:8](=[O:10])[CH2:9][CH:4]([CH2:1][CH:2]=[CH2:3])[C:5]1=[O:7])[CH:14]=[CH2:15]
Reactant: C=CCC1CC(=O)OC1=O
Reactant: c1ccncc1
Agent: [Na]
Solvent: CCOCC
Product: C=CCC1CC(=O)N(CC=C)C1=O
Reaction time: 2 h
Yield: 89.9 %

Procedure:
About 140 g (1 mol) of allylsuccinic anhydride and 250 ml of diethyl ether which has been dried over metallic sodium are placed under nitrogen in a round-bottomed flask equipped with a stirrer, dropping funnel and reflux condenser, and then mixed with 75 g (0.95 mol) of pyridine. About 57 g of allylamine in 100 ml of diethyl ether which has been dried over metallic sodium are then added dropwise to the flask with stirring over a period of 2 hours. When the addition is complete, the mixture is refluxed for an additional 1 hour. The resultant mixture is washed in a separating funnel with 5 percent aqueous hydrochloric acid until the pH of the aqueous phase is 6.5. The organic phase is dried over magnesium sulfate. After filtering off the drying agent, the solvent is removed at 15 hPa (abs.). About 153 g of N-allyl-allylsuccinimide, which boils at 130° C. at 0.5 hPa, are obtained from the residue by distillation.
Reaction SMILES: Cl.[NH2:2][CH2:3][CH2:4][NH:5][C:6](=[O:14])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[Cl:13].C(N(CC)CC)C.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>ClCCl>[Cl:13][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[C:6]([NH:5][CH2:4][CH2:3][NH:2][S:23]([CH3:22])(=[O:25])=[O:24])=[O:14]
Reactant: CS(=O)(=O)Cl
Reactant: NCCNC(=O)c1ccccc1Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)NCCNC(=O)c1ccccc1Cl

Procedure:
N-(2-Aminoethyl)-2-chlorobenzamide hydrochloride was suspended in dichloromethane and stirred with triethylamine and methanesulfonyl chloride to obtain 2-chloro-N-{2-[(methylsulfonyl)amino]ethyl}benzamide.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[Br:6][C:7]1[CH:8]=[C:9]([NH2:14])[C:10]([CH3:13])=[N:11][CH:12]=1.Cl.C(Cl)Cl>N1C=CC=CC=1>[Br:6][C:7]1[CH:8]=[C:9]([NH:14][S:2]([CH3:1])(=[O:4])=[O:3])[C:10]([CH3:13])=[N:11][CH:12]=1
Reactant: Cc1ncc(Br)cc1N
Reactant: CS(=O)(=O)Cl
Agent: Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: Cc1ncc(Br)cc1NS(C)(=O)=O

Procedure:
Methanesulfonyl chloride (97 μl) was added dropwise to 5-bromo-2-methyl-3-pyridinamine (Chempacific) (200 mg) in pyridine (5 ml). The reaction was stirred at room temperature for 20 min before addition of 2M HCl (aq) (5 ml) and extraction into DCM. The DCM was passed through a hydrophobic frit then dried under a stream of nitrogen. The residue was dissolved in DCM and washed through an aminopropyl cartridge (preconditioned with DCM) with DCM to give title compound, 77 mg.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[N+:10]([O-])([OH:12])=[O:11]>OS(O)(=O)=O>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11]
Reactant: O=[N+]([O-])O
Reactant: N#Cc1ccc(Br)cc1
Agent: O=S(=O)(O)O
Product: N#Cc1ccc(Br)c([N+](=O)[O-])c1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 56 %

Procedure:
To a solution of 4-bromobenzonitrile (4.0 g, 22 mmol) in conc. H2SO4 (10 mL) was added dropwise at 0° C. nitric acid (6 mL). The reaction mixture was stirred at 0° C. for 30 min, and then at room temperature for 2.5 h. The resulting solution was poured into ice-water. The white precipitate was collected via filtration and washed with water until the washings were neutral. The solid was recrystallized from an ethanol/water mixture (1:1, 20 mL) twice to afford 4-bromo-3-nitrobenzonitrile as a white crystalline solid (2.8 g, 56%). 1H NMR (300 MHz, DMSO-d6) δ 8.54 (s, 1H), 8.06 (d, J=8.4 Hz, 1H), 7.99 (d, J=8.4 Hz, 1H); 13C NMR (75 MHz, DMSO-d6) δ 150.4, 137.4, 136.6, 129.6, 119.6, 117.0, 112.6; HPLC ret. time 1.96 min, 10-100% CH3CN, 5 min gradient; ESI-MS 227.1 m/z (MH+).
Reaction SMILES: [OH-].[Na+].CCO.[Cl:6][C:7]1[C:8]([N:34]2[CH2:39][CH2:38][CH:37]([C:40]([O:42]CC)=[O:41])[CH2:36][CH2:35]2)=[N:9][CH:10]=[C:11]([C:13](=[O:33])[NH:14][C:15]2[S:16][C:17]([CH2:26][N:27]([CH2:29][CH2:30][O:31][CH3:32])[CH3:28])=[C:18]([C:20]3[S:21][CH:22]=[C:23]([Cl:25])[CH:24]=3)[N:19]=2)[CH:12]=1.Cl>O>[ClH:6].[Cl:6][C:7]1[C:8]([N:34]2[CH2:39][CH2:38][CH:37]([C:40]([OH:42])=[O:41])[CH2:36][CH2:35]2)=[N:9][CH:10]=[C:11]([C:13](=[O:33])[NH:14][C:15]2[S:16][C:17]([CH2:26][N:27]([CH2:29][CH2:30][O:31][CH3:32])[CH3:28])=[C:18]([C:20]3[S:21][CH:22]=[C:23]([Cl:25])[CH:24]=3)[N:19]=2)[CH:12]=1
Reactant: CCOC(=O)C1CCN(c2ncc(C(=O)Nc3nc(-c4cc(Cl)cs4)c(CN(C)CCOC)s3)cc2Cl)CC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: COCCN(C)Cc1sc(NC(=O)c2cnc(N3CCC(C(=O)O)CC3)c(Cl)c2)nc1-c1cc(Cl)cs1
Temperature: 60 °C
Reaction time: 2 h
Yield: 189.5 %

Procedure:
0.4 ml of a 1M sodium hydroxide aqueous solution was added to a 1.5 ml EtOH suspension of 76 mg of ethyl 1-{3-chloro-5-[(4-(4-chlorothiophen-2-yl)-5-{[(2-methoxyethyl)(methyl)amino]methyl}thiazol-2-yl)carbamoyl]-2-pyridyl}piperidine-4-carboxylate, and the mixture was stirred at 60° C. for 2 hours. 0.6 ml of 1M hydrochloric acid and 0.5 ml of water were added at room temperature, and the resulting precipitate was collected by filtration, washed with 50% ethanol water, and dried under reduced pressure to obtain 73 mg of 1-{3-chloro-5-[(4-(4-chlorothiophen-2-yl)-5-{[(2-methoxyethyl)(methyl)amino]methyl}thiazol-2-yl)carbamoyl]-2-pyridyl}piperidine-4-carboxylic acid hydrochloride.
Reaction SMILES: [Na].Cl.[Cl:3][C:4]1[CH:5]=[C:6]([NH:11][NH2:12])[CH:7]=[CH:8][C:9]=1[Cl:10].[C:13](#[N:16])[CH:14]=[CH2:15]>C(O)C>[NH2:16][C:13]1[CH2:14][CH2:15][N:11]([C:6]2[CH:7]=[CH:8][C:9]([Cl:10])=[C:4]([Cl:3])[CH:5]=2)[N:12]=1
Reactant: C=CC#N
Reactant: NNc1ccc(Cl)c(Cl)c1
Agent: Cl
Agent: [Na]
Solvent: CCO
Product: NC1=NN(c2ccc(Cl)c(Cl)c2)CC1
Reaction time: 0.17 h

Procedure:
A 2.8 g. amount of sodium metal is dissolved in 200 ml. of absolute ethanol, then 21.35 g. of 3,4-dichlorophenylhydrazine hydrochloride is added followed in 10 minutes by 5.5 g. of acrylonitrile. The reaction mixture is refluxed for 4 hours then most of the ethanol is removed in vacuo. Water is added to separate a solid. The solid is collected by filtration and dried. The solid is dissolved in methanol, treated with activated charcoal and filtered. The filtrate is evaporated to give a solid. The solid is recrystallized from methanol to give the desired product as tan crystals, m.p. 182°-183.5° C.
Reaction SMILES: Cl.[C:2]1([CH2:8][C:9]([NH2:11])=[NH:10])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:12][C:13]([SH:16])(Cl)Cl.[OH-].[Na+]>ClCCl.O>[CH2:8]([C:9]1[N:11]=[C:13]([Cl:12])[S:16][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: SC(Cl)(Cl)Cl
Reactant: N=C(N)Cc1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Product: Clc1nc(Cc2ccccc2)ns1
Temperature: -10 °C
Reaction time: 0.17 h

Procedure:
To a suspension of 2-phenyl-acetamidine hydrochloride (1.078 g, 6 mmol) in dichloromethane (10 ml) was added perchloromethyl mercaptan (0.61 ml, 5 mmol) via syringe. The mixture was cooled in an ice-methanol bath to −10° C. and a solution of sodium hydroxide (1.2 g, 30 mmol) in water (3 ml) was added dropwise keeping the temperature below −8° C. After complete addition the mixture was stirred 10 min at 0° C. The reaction mixture was diluted with water and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were dried over Na2SO4, filtered and the solvents were evaporated. The residue was purified by chromatography on silica gel using heptane/ethyl acetate as eluent. The title compound was obtained as an orange liquid (0.779 g, 62%). MS ISP (m/e): 211.0 (100) [(M+H)+].
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1.[CH3:11][NH:12][CH3:13]>C(O)C.C(Cl)Cl>[CH3:11][N:12]([CH3:13])[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][N:3]=1
Reactant: O=[N+]([O-])c1ccc(Cl)nc1
Reactant: CNC
Solvent: CCO
Solvent: ClCCl
Product: CN(C)c1ccc([N+](=O)[O-])cn1
Temperature: 75 °C
Yield: 100.1 %

Procedure:
A mixture of 2-chloro-5-nitropyridine (5.0 g, 31.5 mmol) and 40% solution of Dimethylamine (10.66 g, 95 mmol) in ethanol (40 mL) was heated to 75° C. for 1 hour. The mixture was cooled to ambient temperature, diluted with CH2Cl2 and washed with saturated aqueous NaHCO3 (3×100 mL) and brine. The organic was dried (MgSO4), filtered and concentrated to afford 5.27 g (100%) of the title compound. MS (ESI) m/z 168 (M+H)+.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH:12]1[C:20]2[C:19]3[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=3[S:17][C:16]=2[CH:15]=[C:14]([CH:25]([N:27]2[CH:31]=[CH:30][N:29]=[CH:28]2)[CH3:26])[CH:13]=1.C(=O)(O)[O-].[Na+].[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]/[C:40]([OH:42])=[O:41]>C(Cl)(Cl)Cl.CC(C)=O>[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]/[C:40]([OH:42])=[O:41].[N:27]1([CH:25]([C:14]2[CH:13]=[CH:12][C:20]3[C:19]4[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=4[S:17](=[O:9])[C:16]=3[CH:15]=2)[CH3:26])[CH:31]=[CH:30][N:29]=[CH:28]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CC(c1ccc2c(c1)sc1ccccc12)n1ccnc1
Agent: O=C(O)/C=C/C(=O)O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)=O
Solvent: ClC(Cl)Cl
Product: CC(c1ccc2c(c1)S(=O)c1ccccc1-2)n1ccnc1
Reaction time: 2 h
Yield: 63.6 %

Procedure:
Under ice-cooling, m-chloroperbenzoic acid (0.18 g) was gradually added in small portions to a solution of 1-[1-(dibenzothiophen-3-yl) ethyl]-1H-imidazole (0.2 g) obtained in Example 8 in chloroform (5 ml), and the mixture was stirred at the same temperature for 2 hours. A saturated sodium bicarbonate aqueous solution was added and the chloroform layer was separated and dried over anhydrous magnesium sulfate. After evaporation of the solvent, the resulting residue was purified by silica gel column chromatography to obtain an oily material from a chloroform-methanol (100:1) eluate. This oily material was dissolved in acetone and mixed with 40 mg of fumaric acid which was dissolved by heating. After cooling, the thus precipitated crystals were washed with acetone to obtain 90 mg of 3-[1-(1H-imidazo1-1-yl)ethyl]dibenzothiophene-5-oxide monofumarate.
Reaction SMILES: [C:1]1([N:7]=[C:8]=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:10][C:11]1[CH:12]=[C:13]([CH:29]=[CH:30][CH:31]=1)[CH2:14][NH:15][C:16]1[C:25]2[C:20](=[C:21]([C:26]([NH2:28])=[O:27])[CH:22]=[CH:23][CH:24]=2)[N:19]=[CH:18][N:17]=1.C(N(CC)CC)C>C(Cl)Cl>[NH:7]([C:8]([NH:10][C:11]1[CH:12]=[C:13]([CH:29]=[CH:30][CH:31]=1)[CH2:14][NH:15][C:16]1[C:25]2[C:20](=[C:21]([C:26]([NH2:28])=[O:27])[CH:22]=[CH:23][CH:24]=2)[N:19]=[CH:18][N:17]=1)=[O:9])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C=Nc1ccccc1
Reactant: NC(=O)c1cccc2c(NCc3cccc(N)c3)ncnc12
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: NC(=O)c1cccc2c(NCc3cccc(NC(=O)Nc4ccccc4)c3)ncnc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 34 %

Procedure:
Phenyl isocyanate (240 μL, 0.5 M in anhydrous DCM, 0.11 mmol, 1.1 equiv.) was added to a solution of 4-[(3-aminobenzyl)amino]quinazoline-8-carboxamide (32 mg, 0.1 mmol, 1.0 equiv.) and triethylamine (40 μL, 0.3 mmol, 3.0 equiv.) in anhydrous DCM (2 mL). The resulting mixture was stirred at rt overnight. The title compound was obtained by pre-HPLC in 34% yield. Mass: M+H+: 413.
Reaction SMILES: [CH3:1][C:2]1[C:10]([CH3:11])=[CH:9][C:5]2[NH:6][CH:7]=[N:8][C:4]=2[CH:3]=1.[C:12](Cl)([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>CN(C=O)C.CCOC(C)=O>[CH3:1][C:2]1[C:10]([CH3:11])=[CH:9][C:5]2[N:6]([C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: Cc1cc2nc[nH]c2cc1C
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cc1cc2ncn(C(c3ccccc3)(c3ccccc3)c3ccccc3)c2cc1C
Yield: 98.6 %

Procedure:
A mixture of 5,6-dimethyl-1H-benzo[d]imidazole (500 mg, 3.42 mmol), trityl chloride (1.05 g, 3.76 mmol) and TEA (524 μL, 3.76 mmol) in 5 mL DMF was stirreds at rt for 3 h. The mixture was diluted with EtOAc, washed with H2O and brine, dried (Na2SO4) and concentrated. The crude residue was purified by flash chromatography (0 to 100% EtOAc/hexanes gradient) to afford 1.31 g of Intermediate 415.1.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:21])[C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([C:19]#[N:20])([CH3:18])[CH3:17])[CH:11]=2)=[CH:4][C:3]=1[O:22][C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-])=O)=[CH:25][N:24]=1.[Cl-].[Ca+2].[Cl-].O>C(O)C>[NH2:29][C:26]1[CH:27]=[CH:28][C:23]([O:22][C:3]2[CH:4]=[C:5]([NH:8][C:9](=[O:21])[C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([C:19]#[N:20])([CH3:17])[CH3:18])[CH:11]=3)[CH:6]=[CH:7][C:2]=2[Cl:1])=[N:24][CH:25]=1
Reactant: CC(C)(C#N)c1cccc(C(=O)Nc2ccc(Cl)c(Oc3ccc([N+](=O)[O-])cn3)c2)c1
Agent: [Ca+2]
Agent: [Cl-]
Solvent: CCO
Solvent: O
Product: CC(C)(C#N)c1cccc(C(=O)Nc2ccc(Cl)c(Oc3ccc(N)cn3)c2)c1
Temperature: 90 °C
Yield: 62.3 %

Procedure:
A suspension of N-{4-chloro-3-[(5-nitropyridin-2--yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamide (2.5 g, 5.72 mmol), calcium chloride (2.00 g, 17.2 mmol) and reduced iron (1.43 g, 25.7 mmol) in ethanol (35 mL)/water (5 mL) was stirred with heating at 90° C. for 4 hr. After the reaction mixture was cooled to room temperature, the insoluble material was filtered off through a pad filled with celite, and washed with ethyl acetate. The filtrate and the washing fluid were combined, and concentrated under reduced pressure. The obtained residue was diluted with ethyl acetate (100 mL), washed with water (50 mL×2), 5% aqueous sodium hydrogen carbonate solution (50 mL×2) and saturated brine (50 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate), and the obtained solution was concentrated under reduced pressure to give the title compound (1.45 g, 62%) as a beige amorphous substance.
Reaction SMILES: [CH3:1][O:2][N:3]=[C:4]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=1[CH3:23])[C:5](O)=[O:6].CN(C)C=O.C(Cl)(=O)C([Cl:32])=O>C1(C)C=CC=CC=1>[CH3:1][O:2][N:3]=[C:4]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=1[CH3:23])[C:5]([Cl:32])=[O:6]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CON=C(C(=O)O)c1ccccc1COc1ccc(Cl)cc1C
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: CON=C(C(=O)Cl)c1ccccc1COc1ccc(Cl)cc1C
Reaction time: 1 h

Procedure:
To a mixture of 52.24 g (0.150 mol, E/Z=3.5/96.5) of α-methoxyimino-2-(4-chloro-2-methylphenoxymethyl)phenylacetic acid produced in accordance with Example 5-(2), 0.57 g (0.0078 mol) of dimethylformamide and 203 g of toluene was added dropwise 25.9 g (0.204 mol) of oxalyl chloride over 3 hours while keeping at 60°-65° C., and the reaction was subsequently allowed to proceed at the same temperature for 1 hours and then 80° C. for 2 hours, which afforded 265 g of a toluene solution of α-methoxyimino-2-(4-chloro-2-methylphenoxymethyl)phenylacetyl chloride.
Reaction SMILES: [CH:1]12[CH2:11][CH:8]([CH:9]=[CH:10]1)[CH:7]1[CH:2]2[C:3](=[O:13])[CH:4]=[CH:5][C:6]1=[O:12].C([O-])(O)=[O:15].[Na+].OO.O>CC(C)=O>[O:15]1[CH:4]2[CH:5]1[C:6](=[O:12])[CH:7]1[CH:2]([C:3]2=[O:13])[CH:1]2[CH2:11][CH:8]1[CH:9]=[CH:10]2
Reactant: O=C1C=CC(=O)C2C3C=CC(C3)C12
Reactant: O=C([O-])O
Agent: OO
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: O=C1C2OC2C(=O)C2C3C=CC(C3)C12
Temperature: 0 °C
Reaction time: 1 h
Yield: 98.35 %

Procedure:
A solution of tricyclo[6.2.1.02,7]undeca-4,9-diene-3,6-dione (14) (26.13 g, 150 mmol) in acetone (100 ml) was cooled to 0° C. on an ice-bath. To the solution was added saturated aqueous NaHCO3 (33 ml). To the mixture was added dropwise 34.5% aqueous hydrogen peroxide (142 ml) while keeping at 0° C. After the addition, the reaction mixture was stirred at 0° C. for 1 hr and then water (100 ml) was added. From the mixture solution, the product was extracted with diethyl ether (total 700 ml). The extract was washed with saturated aqueous NaCl and dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to afford as the residue 4,5-epoxy-tricyclo[6.2.1.02,7]undec-9-ene-3,6-dione (15) (28.06 g, 148 mmol, 98.35% yield) in light yellowish white crystals.
Reaction SMILES: [N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:60]=[CH:59][C:14]([CH2:15][N:16]([CH2:49][CH2:50][O:51]CC3C=CC=CC=3)[C:17]3[CH:22]=[C:21]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH:20]=[CH:19][C:18]=3[CH:31]3[CH2:40][CH2:39][C:38]4[C:33](=[CH:34][CH:35]=[C:36]([O:41][Si:42]([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:44])[CH3:43])[CH:37]=4)[CH2:32]3)=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.B(Cl)(Cl)Cl.CO>ClCCl.C(=O)(O)[O-].[Na+]>[N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:60]=[CH:59][C:14]([CH2:15][N:16]([C:17]3[CH:22]=[C:21]([O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[CH:20]=[CH:19][C:18]=3[CH:31]3[CH2:40][CH2:39][C:38]4[C:33](=[CH:34][CH:35]=[C:36]([O:41][Si:42]([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:44])[CH3:43])[CH:37]=4)[CH2:32]3)[CH2:49][CH2:50][OH:51])=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc2c(c1)CCC(c1ccc(O[Si](C)(C)C(C)(C)C)cc1N(CCOCc1ccccc1)Cc1ccc(OCCN3CCCCCC3)cc1)C2
Agent: ClB(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)Oc1ccc2c(c1)CCC(c1ccc(O[Si](C)(C)C(C)(C)C)cc1N(CCO)Cc1ccc(OCCN3CCCCCC3)cc1)C2
Reaction time: 0.5 h
Yield: 59.7 %

Procedure:
To a solution of [4-(2-azepan-1-ylethoxy)benzyl](2-benzyloxyethyl){5-(tert-butyldimethylsilyloxy)-2-[6-(tert-butyldimethylsilyloxy)-1,2,3,4-tetrahydronaphthalen-2-yl]phenyl}amine (450 mg) in dichloromethane (23 ml) was added dropwise boron trichloride (1.0 M solution in dichloromethane) (4.2 ml) at −78° C., and the solution was stirred for 30 minutes. At −78° C., to the reaction solution was added methanol (2 ml), and the reaction mixture was diluted with a saturated aqueous solution of sodium bicarbonate. The solution was extracted with chloroform, then washed with brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified by NH silica gel column chromatography (hexane-ethyl acetate system) to provide the title compound (240 mg).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([SH:8])[CH:5]=[CH:6][CH:7]=1.Cl[C:10]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][C:11]=1[N+:17]([O-:19])=[O:18].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[CH3:16][C:13]1[CH:14]=[CH:15][C:10]([S:8][C:4]2[CH:3]=[C:2]([NH2:1])[CH:7]=[CH:6][CH:5]=2)=[C:11]([N+:17]([O-:19])=[O:18])[CH:12]=1
Reactant: Nc1cccc(S)c1
Reactant: Cc1ccc(Cl)c([N+](=O)[O-])c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc(Sc2cccc(N)c2)c([N+](=O)[O-])c1
Temperature: 100 °C
Yield: 33 %

Procedure:
The title compound was prepared from 3-Amino-benzenethiol (5.034 g, 40.21 mmol), 1-Chloro-4-methyl-2-nitro-benzene (4.600 g, 26.81 mmol) and K2CO3 (6.484 g, 46.92 mmol) dissolved in DMF and heated to 100° C. for 16 hrs. At this time the reaction mixture was cooled to room temperature and diluted with water, extracted with ethyl acetate. Dried over Na2SO4, filtered and concentrated under vacuum giving the title compound (2.3 g, 32%).
Reaction SMILES: [C:1]([O:4][C:5]1([CH2:19][N:20]([CH:24]([CH3:26])[CH3:25])[C:21](=[O:23])[CH3:22])[CH2:11][O:10][C:9]2[CH:12]=[CH:13][C:14]([N+:16]([O-])=O)=[CH:15][C:8]=2[O:7][CH2:6]1)(=[O:3])[CH3:2].[H][H]>C(OCC)(=O)C.[Pt]>[C:1]([O:4][C:5]1([CH2:19][N:20]([CH:24]([CH3:26])[CH3:25])[C:21](=[O:23])[CH3:22])[CH2:11][O:10][C:9]2[CH:12]=[CH:13][C:14]([NH2:16])=[CH:15][C:8]=2[O:7][CH2:6]1)(=[O:3])[CH3:2]
Reactant: [H][H]
Reactant: CC(=O)OC1(CN(C(C)=O)C(C)C)COc2ccc([N+](=O)[O-])cc2OC1
Agent: [Pt]
Solvent: CCOC(C)=O
Product: CC(=O)OC1(CN(C(C)=O)C(C)C)COc2ccc(N)cc2OC1

Procedure:
The 3-acetoxy-3-(N-acetylisopropylaminomethyl)-7-nitro-3,4-dihydro-2H-1,5-benzodioxepin when dissolved in ethyl acetate is reduced at low pressure over platinum with hydrogen to give 3-acetoxy-3-(N-acetylisopropylaminomethyl)-7-amino-3,4-dihydro-2H-1,5-benzodioxepin.