Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[CH2:17][N:16]4[CH:12]([CH2:13][CH2:14][CH2:15]4)[CH2:11][C:7]=3[NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].[S:20](Cl)([C:23]1[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=1)(=[O:22])=[O:21]>C1COCC1>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]3[CH2:17][N:16]4[CH:12]([CH2:13][CH2:14][CH2:15]4)[CH2:11][C:7]=3[N:8]2[S:20]([C:23]2[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=2)(=[O:22])=[O:21])=[CH:4][CH:3]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: Brc1ccc2c3c([nH]c2c1)CC1CCCN1C3
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1ccc(S(=O)(=O)n2c3c(c4ccc(Br)cc42)CN2CCCC2C3)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 47.5 %

Procedure:
A solution of 8-Bromo-2,3,5,10,11,11a-hexahydro-1H-indolizino[7,6-b]indole (150 mg, 0.52 mmol) in THF (3 mL) was treated sequentially with NaH (31 mg, 0.77 mmol) and TsCl (0.12 g, 0.61 mmol). The reaction mixture was stirred at room temperature under argon overnight. After the mixture was concentrated, the residue was purified by flash column chromatography (silica gel, 5% CH3OH in CH2Cl2) to give 8-bromo-10-tosyl-2,3,5,10,11,11a-hexahydro-1H-indolizino[7,6-b]indole (0.11 g, 48%) as a yellow solid. 8-bromo-10-tosyl-2,3,5,10,11,11a-hexahydro-1H-indolizino[7,6-b]indole (0.11 g, 0.22 mmol) was reacted according to the procedure of Example 2 (step b) to give a yellow solid in 40% (50 mg). The yellow solid was dissolved in CH2Cl2, and NaOH (177 mg, 4.43 mmol) was added. The reaction mixture was stirred at room temperature under argon for 3 h. After the mixture was concentrated, the residue was purified by flash column chromatography (silica gel, 10% CH3OH in CH2Cl2) to give a white solid (30 mg, 83%). The white solid was dissolved in CH3OH (1 mL) and was treated with 2 N HCl in Et2O (1 mL). The resulting solid was isolated by filtration and dried under vacuum to give the title compound (30 mg, 92%) as an off-white powder: mp 270-273° C.; 1H NMR (500 MHz, CD3OD) δ 7.61 (d, J=8.0 Hz, 1H), 7.57 (d, J=8.0 Hz, 1H), 7.47-7.31 (m, 6H), 7.04 (dd, J=8.5, 2.0 Hz, 1H), 6.36-6.34 (m, 1H), 6.16 (d, J=2.5 Hz, 1H), 5.20 (s, 2H), 4.89 (d, J=14.0 Hz, 1H), 4.36 (d, J=14.0 Hz, 1H), 3.90-3.85 (m, 2H), 3.49-3.36 (m, 2H), 3.10 (dd, J=15.5, 11.0 Hz, 1H), 2.60-2.55 (m, 1H), 2.36-2.21 (m, 2H), 1.96-1.92 (m, 1H); ESI MS m/z 412 [M+H]+; HPLC (Method A)>99% (AUC), tR=12.7 min.
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[C:6]([Cl:11])[N:5]=[C:4]([CH3:12])[N:3]=1.C([Sn](CCCC)(CCCC)[C:18]([O:20][CH2:21][CH3:22])=[CH2:19])CCC.[F-].[K+]>O1CCCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:11][C:6]1[C:7]([N+:8]([O-:10])=[O:9])=[C:2]([C:18]([O:20][CH2:21][CH3:22])=[CH2:19])[N:3]=[C:4]([CH3:12])[N:5]=1
Reactant: Cc1nc(Cl)c([N+](=O)[O-])c(Cl)n1
Reactant: C=C(OCC)[Sn](CCCC)(CCCC)CCCC
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [F-]
Agent: [K+]
Solvent: C1CCOC1
Product: C=C(OCC)c1nc(C)nc(Cl)c1[N+](=O)[O-]
Temperature: 85 °C

Procedure:
A mixture of 4,6-dichloro-2-methyl-5-nitropyrimidine (3.12 g), tributyl(1-ethoxy-vinyl)tin (5.3 mL) and dichlorobis(triphenylphosphine)palladium(II) (0.53 g) in tetrahydrofuran (60 mL) was stirred at 85° C. under an argon atmosphere in a reaction vessel equipped with a reflux condenser for 4 hours. The reaction mixture was cooled to room temperature. To the mixture was added 0.5 mol/L aqueous potassium fluoride solution (20 mL), and the resulting mixture was stirred at room temperature for 1 hour. The insoluble material was removed by filtration, and the insoluble material was washed with ethyl acetate. The filtrate and washing were combined, and the organic layer was separated. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=20/1−4/1). The product was dissolved in ethyl acetate. To the solution were added 0.5 mol/L aqueous potassium fluoride solution (20 mL) and water (20 mL), and the mixture was stirred at room temperature for 30 minutes. The insoluble material was removed by filtration, and the filtrate was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give 4-chloro-6-(1-ethoxyvinyl)-2-methyl-5-nitropyrimidine (3.65 g). This material was dissolved in acetone (30 mL). To the solution was added p-toluenesulfonic acid monohydrate (2.28 g), and the mixture was heated at reflux for 4 hours. The reaction mixture was cooled to room temperature, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=20/1−4/1) to give the title compound (2.32 g).
Reaction SMILES: C(O)(=O)C.[CH3:5][O:6][C:7]1[C:18]([O:19][CH3:20])=[CH:17][C:10]2[CH2:11][C:12](=O)[NH:13][CH2:14][CH2:15][C:9]=2[CH:8]=1.[BH4-].[Na+]>O1CCOCC1>[CH3:5][O:6][C:7]1[C:18]([O:19][CH3:20])=[CH:17][C:10]2[CH2:11][CH2:12][NH:13][CH2:14][CH2:15][C:9]=2[CH:8]=1
Reactant: COc1cc2c(cc1OC)CC(=O)NCC2
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: C1COCCO1
Product: COc1cc2c(cc1OC)CCNCC2

Procedure:
A solution of 1.8 gm of glacial acetic acid in 10 ml of dioxane was added dropwise to a suspension of 1.3 gm (6 mmols) of 7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-one and 1.1 gm (3 mmols) of sodium borohydride in 20 ml of dioxane; the mixture was refluxed for 3 hours, concentrated by evaporation and mixed with water. The mixture was extracted twice by shaking with methylene chloride; the extract was concentrated by evaporation, and the residue was taken up in ether. After filtering, the ether was removed in vacuo.
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([CH3:13])=[CH:9]2)([CH3:3])[CH3:2].[CH3:14]N(C=O)C.[H-].[Na+].IC>CCOCC>[CH:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[N:11]([CH3:14])[C:10]([CH3:13])=[CH:9]2)([CH3:3])[CH3:2]
Reactant: Cc1cc2cccc(C(C)C)c2[nH]1
Reactant: CN(C)C=O
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: CCOCC
Product: Cc1cc2cccc(C(C)C)c2n1C
Reaction time: 1 h
Yield: 41 %

Procedure:
To a solution of 7-isopropyl-2-methyl-1H-indole (0.75 g, 4.33 mmol) and DMF (2 mL) is added 60% NaH (0.19 g, 4.76 mmol). After 30 minutes iodomethane (0.30 mL, 4.76 mmol) is added and the solution stirred for 1 hour. The solution is diluted with Et2O (30 mL), washed with water (2×20 mL), brine (20 mL) dried over MgSO4, filtered and concentrated. The residue is purified by ISCO (2%-5% EtOAc gradient) to furnish the title compound (0.33 g, 1.76 mmol, 41%). 1H NMR (CDCl3), δ 1.42 (d, J=6.5 Hz, 6H), 2.43 (s, 3H), 3.84-3.91 (m, 1H), 6.24-6.27 (m, 1H), 3.93 (s, 1H), 6.29 (s, 1H), 7.01-7.14 (m, 1H), 7.38 (d, J=7.5 Hz, 1H) ppm. LC/MS (m/z): calcd. for C13H17N (M+H)+: 188.2. found: 188.1.
Reaction SMILES: [CH:1]([N:14]1[CH2:17][CH:16]([CH2:18]O)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)([Cl:22])=O>ClCCl>[ClH:22].[CH:1]([N:14]1[CH2:17][CH:16]([CH2:18][Cl:22])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: OCC1CN(C(c2ccccc2)c2ccccc2)C1
Solvent: ClCCl
Product: Cl
Product: ClCC1CN(C(c2ccccc2)c2ccccc2)C1
Temperature: 2.5 °C
Reaction time: 18 h
Yield: 168.9 %

Procedure:
(1-Benzhydryl-azetidin-3-yl)-methanol (3.07 g, 12.1 mmol) was dissolved in dichloromethane (60 ml). The reaction was cooled to 0-5° C. and thionyl chloride (1.07 ml, 14.6 mmol) was added slowly. The reaction was allowed to warm to room temperature and stirred for 18 hours. The reaction was concentrated in vacuo and azeotroped with toluene (3×20 ml) to give the title compound (3.8 g, 100%) as a pale brown solid.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[CH2:12][N:11]([CH2:16][C:17]([N:19]1[CH2:24][CH2:23][N:22]([CH:25]3[CH2:28][CH2:27][CH2:26]3)[CH2:21][CH2:20]1)=[O:18])[CH2:10][CH2:9]2)=[O:5])C.[OH-].[Li+]>C1COCC1.CO.O>[CH:25]1([N:22]2[CH2:21][CH2:20][N:19]([C:17](=[O:18])[CH2:16][N:11]3[CH2:10][CH2:9][C:8]4[C:13](=[CH:14][CH:15]=[C:6]([C:4]([OH:5])=[O:3])[CH:7]=4)[CH2:12]3)[CH2:24][CH2:23]2)[CH2:26][CH2:27][CH2:28]1
Reactant: CCOC(=O)c1ccc2c(c1)CCN(CC(=O)N1CCN(C3CCC3)CC1)C2
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)c1ccc2c(c1)CCN(CC(=O)N1CCN(C3CCC3)CC1)C2
Temperature: 0 °C
Reaction time: 8 h

Procedure:
To a solution of 2-[2-(4-cyclobutyl-piperazin-1-yl)-2-oxo-ethyl]-1,2,3,4-tetrahydro-isoquinoline-6-carboxylic acid ethyl ester (610 mg, 1.58 mmol) in a mixture of THF-MeOH-water (3:1:1, 5 ml) cooled to 0° C. is added lithium hydroxide (76 mg, 3.16 mmol, 2.0 eq.). The mixture is stirred at rt overnight. The organic solvent is evaporated, and the residue is acidified to pH=5 with hydrochloric acid (2.0 N, about 1.58 ml). The resulting aqueous solution is evaporated to dryness, and the residue is extracted with a DCM-EtOH mixture (9:1, 10 ml×4). The combined organic solution is dried over sodium sulfate, and concentrated to give the title compound. MS (+VE) m/z 356.2 (M++1).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:51])[NH:4][C@@H:5]([C:47]([CH3:50])([CH3:49])[CH3:48])[C:6](=[O:46])[NH:7][C@@H:8]([CH2:33][C:34]1[CH:39]=[CH:38][C:37]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=2)=[CH:36][CH:35]=1)[C@@H:9]([OH:32])[CH2:10][C@H:11]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[NH:12][C:13](=[O:24])[C@H:14]([C:20]([CH3:23])([CH3:22])[CH3:21])[NH:15][C:16](=[O:19])[O:17][CH3:18].[CH3:52][S:53][CH3:54].C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(#N)C.C(OCC)(=O)C>[CH2:25]([C@H:11]([NH:12][C:13]([C@@H:14]([NH:15][C:16](=[O:19])[O:17][CH3:18])[C:20]([CH3:23])([CH3:22])[CH3:21])=[O:24])[CH2:10][C@H:9]([O:32][CH2:52][S:53][CH3:54])[C@@H:8]([NH:7][C:6](=[O:46])[C@H:5]([C:47]([CH3:50])([CH3:49])[CH3:48])[NH:4][C:3]([O:2][CH3:1])=[O:51])[CH2:33][C:34]1[CH:35]=[CH:36][C:37]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=2)=[CH:38][CH:39]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: CSC
Reactant: COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C[C@H](O)[C@H](Cc1ccc(-c2ccccn2)cc1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C(C)(C)C
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: CC#N
Solvent: CCOC(C)=O
Product: COC(=O)N[C@H](C(=O)N[C@@H](Cc1ccccc1)C[C@H](OCSC)[C@H](Cc1ccc(-c2ccccn2)cc1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C(C)(C)C
Temperature: 0 °C
Reaction time: 1 h
Yield: 76.5 %

Procedure:
To a solution of the compound of Example 25 (0.125 g, 0.178 mmol) and methyl sulfide (0.405 mL, 5.48 mmol) in acetonitrile (0.75 mL) at 0° C. was added benzoyl peroxide (0.63 g, 2.60 mmol), and the mixture was stirred at 0° C. for 1 hour. The reaction was diluted with ethyl acetate and washed with 10% Na2CO3 and brine. The organic was dried over MgSO4, filtered and evaporated. The residue was chromatographed on silica gel eluting with a gradient starting with dichloromethane and ending with ethyl acetate to give the title compound (0.104 g, 77% yield).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]#[N:9])=[CH:4][N:3]=1.[SH:10][CH2:11][CH2:12][NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17].N12CCCN=C1CCCCC2>CN(C=O)C.O>[C:8]([C:5]1[CH:6]=[CH:7][C:2]([S:10][CH2:11][CH2:12][NH:13][C:14](=[O:20])[O:15][C:16]([CH3:18])([CH3:17])[CH3:19])=[N:3][CH:4]=1)#[N:9]
Reactant: N#Cc1ccc(Cl)nc1
Reactant: CC(C)(C)OC(=O)NCCS
Solvent: CN(C)C=O
Solvent: O
Solvent: C1CCC2=NCCCN2CC1
Product: CC(C)(C)OC(=O)NCCSc1ccc(C#N)cn1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
2-Chloro-5-cyanopyridine (500 mg, 3.6 mmol), tert-butyl (2-mercaptoethyl)carbamate (426 mg, 2.4 mmol) and 1,8-diazabicyclo(5.4.0)undec-7-ene (549 mg, 3.6 mmol) are dissolved in DMF (5 ml) and stirred at RT under argon for 12 h. The reaction mixture is diluted with water (100 ml) and extracted with ethyl acetate (3×75 ml). The combined organic phases are washed with saturated aqueous sodium chloride solution, dried over magnesium sulphate and concentrated. After removal of the solvent, the residue is purified by preparative RP-HPLC (gradient of eluent: water/acetonitrile 90:10 to 10:90). 612 mg (91% of theory) of the product are obtained as a solid.
Reaction SMILES: Br[CH2:2][C:3](=[O:9])[C:4]([CH3:8])([CH3:7])[CH2:5][Cl:6].[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Cl:6][CH2:5][C:4]([CH3:8])([CH3:7])[C:3](=[O:9])[CH2:2][O:17][C:14]1[CH:15]=[CH:16][C:11]([Cl:10])=[CH:12][CH:13]=1
Reactant: Oc1ccc(Cl)cc1
Reactant: CC(C)(CCl)C(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(C)(CCl)C(=O)COc1ccc(Cl)cc1
Yield: 80.4 %

Procedure:
213.5 g (1 mol) of 1-bromo-4-chloro-3,3-dimethyl-butan-2-one were added dropwise to a boiling suspension of 128.5 g (1 mol) of 4-chlorophenol and 140 g (1 mol) of potassium carbonate in 1,000 ml of absolute acetone. The mixture was stirred under reflux for 15 hours and then allowed to cool and the inorganic residue was filtered off and rinsed with acetone. The filtrate was concentrated by distilling off the solvent in vacuo, the residue was taken up in 1,000 ml of methylene chloride and the methylene chloride mixture was washed three times with 250 ml of water each time, dried over sodium sulphate and distilled. 210 g (80.7% of theory) of 4-chloro-1-(4-chlorophenoxy)-3,3-dimethyl-butan-2-one of boiling point 125°-127° C./0.1 mm were obtained.
Reaction SMILES: [C@H]12O[C@H:6]1[CH2:5][CH2:4][C@@H:3]([NH:8][C:9](=O)OC(C)(C)C)C2.C1(C(C2C=CC=CC=2)(C2C=CC=CC=2)S)C=CC=CC=1.[C:36](#[N:38])[CH3:37]>>[CH2:4]1[CH2:3][N:8]2[C:6](=[N:38][CH2:36][CH2:37][CH2:9]2)[CH2:5]1
Reactant: CC(C)(C)OC(=O)N[C@@H]1CC[C@@H]2O[C@@H]2C1
Reactant: CC#N
Agent: SC(c1ccccc1)(c1ccccc1)c1ccccc1
Product: C1CN=C2CCCN2C1

Procedure:
1 g of tert-butyl (1R,3R,6S)-(7-oxa-bicyclo[4.1.0]hept-3-yl)-carbamate (Example 1 Step E), 1.56 g of triphenylmethanethiol, and 16.4 mL of acetonitrile were charged to a flask. To the mixture obtained 560 μL of DBN was added, and the mixture obtained was heated to 40° C. and stirred for 22.5 h. Upon completion of the reaction (TLC), the mixture obtained was cooled to rt, diluted with EtOAc, and washed with H2O and brine. The organic layer obtained was dried over MgSO4, concentrated in vacuo and the crude product obtained was subjected to column chromatography (eluent: cyclohexane/EtOAc 5:1). The required fractions were identified, combined and concentrated in vacuo.
Reaction SMILES: [CH3:1][C:2]1([CH3:17])[C:6](=[O:7])[CH:5]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:16])=[O:15])=[CH:10][CH:9]=2)[O:3]1.FC(F)(F)C(O[I:23](C1C=CC=CC=1)OC(=O)C(F)(F)F)=O.II>C(Cl)(Cl)(Cl)Cl.C(Cl)(Cl)Cl>[CH3:1][C:2]1([CH3:17])[C:6](=[O:7])[C:5]([I:23])=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:16])=[O:15])=[CH:10][CH:9]=2)[O:3]1
Reactant: O=C(OI(OC(=O)C(F)(F)F)c1ccccc1)C(F)(F)F
Reactant: CS(=O)c1ccc(C2=CC(=O)C(C)(C)O2)cc1
Agent: II
Solvent: ClC(Cl)(Cl)Cl
Solvent: ClC(Cl)Cl
Product: CS(=O)c1ccc(C2=C(I)C(=O)C(C)(C)O2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 99.9 %

Procedure:
To a stirred solution of 6 g of 2,2-dimethyl-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone in 200 ml carbon tetrachloride and 100 ml chloroform, were added 5.15 g of [bis(trifluoroacetoxy)iodo]benzene (BTI) and 6.5 g of iodine. The reaction solution was stirred at room temperature. After 4 hours, the reaction was quenched by adding saturated aqueous sodium thiosulfate until the characteristic color of iodine disappeared. The quenched solution was extracted with water and dichloromethane (100 ml×3). The organic layer was concentrated in vacuo and the resulting crude product was recrystallized from hexane/ethylacetate to yield 4.5 g of 2,2-dimethyl-4-iodo-5-{4-(methylsulfinyl)phenyl}-3(2H)-furanone. NMR: δ1.53 (s, 6H), 2.79 (s, 3H), 7.81 (d, J=8.1 Hz, 2H), 8.38 (d, J=8.1 Hz, 2H). IR (cm−1): 2975, 2929, 1699, 1595, 1404, 1319, 1150, 969, 766, 552.
Reaction SMILES: [CH2:1]1[CH2:5][O:4][CH2:3][CH2:2]1.[C:6]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC(N=NC(OC(C)C)=O)=O)(C)C.[Si](OC1[CH:48]=[CH:49][C:50]2[C:62](=[O:63])[C:61]3[C:60]4[C:55](=[CH:56][C:57]([C:64]#[N:65])=[CH:58][CH:59]=4)[NH:54][C:53]=3[C:52]([CH3:67])([CH3:66])C=2C=1)(C(C)(C)C)(C)C>CO>[CH3:3][O:4][C:5]1[CH:48]=[CH:49][C:50]2[C:62](=[O:63])[C:61]3[C:60]4[C:55](=[CH:56][C:57]([C:64]#[N:65])=[CH:58][CH:59]=4)[N:54]([CH3:6])[C:53]=3[C:52]([CH3:67])([CH3:66])[C:2]=2[CH:1]=1
Reactant: CC1(C)c2cc(O[Si](C)(C)C(C)(C)C)ccc2C(=O)c2c1[nH]c1cc(C#N)ccc21
Reactant: C1CCOC1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Solvent: CO
Product: COc1ccc2c(c1)C(C)(C)c1c(c3ccc(C#N)cc3n1C)C2=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 41 %

Procedure:
To the THF solution of triphenylphosphine (260 mg, 3 eq.), azodicarboxylic acid diisopropyl ester (0.195 ml, 3 eq.) was added and the mixture was stirred at room temperature for 1 hr. Thereafter, 8-(tert-butyldimethylsilanyloxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A10, 138 mg, 0.331 mmol) and methanol (1 ml) were added and stirred overnight. The reaction solution was purified by HPLC to obtain the target compound (44.8 mg, 41%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17](=[O:18])[C:16]3[C:11](=[C:12]([CH:32]=O)[C:13](OS(C4C(C)=CC(C)=CC=4C)(=O)=O)=[CH:14][CH:15]=3)[O:10][C:9]=2[CH:34]([CH3:36])[CH3:35])=[CH:4][CH:3]=1.S([O-])([O-])(=O)=O.[Mg+2].C([O-])(=O)C.[NH4+:47].O.[NH2:49]N>C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17](=[O:18])[C:16]3[C:11]([O:10][C:9]=2[CH:34]([CH3:36])[CH3:35])=[C:12]2[C:13](=[CH:14][CH:15]=3)[NH:49][N:47]=[CH:32]2)=[CH:4][CH:3]=1
Reactant: [NH4+]
Reactant: Cc1cc(C)c(S(=O)(=O)Oc2ccc3c(=O)c(-c4ccc(Cl)cc4)c(C(C)C)oc3c2C=O)c(C)c1
Reactant: NN
Agent: CC(=O)[O-]
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Solvent: O
Solvent: CCO
Product: CC(C)c1oc2c(ccc3[nH]ncc32)c(=O)c1-c1ccc(Cl)cc1
Temperature: 145 °C

Procedure:
To a suspension of 2,4,6-trimethylbenzenesulfonic acid 3-(4-chlorophenyl)-8-formyl-2-isopropyl-4-oxo-4H-chromen-7-yl ester (391 mg, 0.745 mmol), magnesium sulphate (450 mg, 3.72 mmol) and ammonium acetate (230 mg, 2.98 mmol) in ethanol (15 ml) in a 20 ml microwave tube is added hydrazine hydrate (0.93 ml, 2.98 mmol). The tube is sealed and heated at 145° C. for ca. 80 min. The mixture is cooled to room temperature, and the volatiles are evaporated under reduced pressure. The residue is dissolved in dry pyridine (14 ml), the solution is transferred to a 20 ml microwave tube, the tube is sealed, and the mixture is heated at 190° C. for 100 min. The mixture is cooled and evaporated to dryness. The residue is purified by chromatography on silica gel using cyclohexane/ethyl acetate (6:1) as eluant.
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([C:11](=[O:13])[CH3:12])=[CH:4][C:3]=1[N+:14]([O-:16])=[O:15].[CH:17]1[CH:22]=[CH:21]C=CC=1>C(NCCC)CC>[N+:14]([C:3]1[CH:4]=[C:5]([C:11](=[O:13])[CH3:12])[CH:6]=[C:7]([N+:8]([O-:10])=[O:9])[C:2]=1[N:8]([CH2:17][CH2:22][CH3:21])[CH2:7][CH2:6][CH3:5])([O-:16])=[O:15]
Reactant: c1ccccc1
Reactant: CC(=O)c1cc([N+](=O)[O-])c(Cl)c([N+](=O)[O-])c1
Solvent: CCCNCCC
Product: CCCN(CCC)c1c([N+](=O)[O-])cc(C(C)=O)cc1[N+](=O)[O-]

Procedure:
To a solution of 8.9 grams (0.0365 mole) of 4'-chloro-3',5'-dinitroacetophenone in 100 milliliters of benzene, 51 milliliters of di-n-propylamine was slowly added with stirring. The resulting mixture was refluxed for 3 hours. The precipitated dipropylamine hydrochloride was separated by filtration. Evaporation of the filtrate to dryness in vacuo yielded a brown solid weighing 11.5 grams (94.5 percent of the theory). Recrystallization from hexane yielded 8.5 grams of an orange colored crystalline compound, melting point 71°-72° C. Anal. calcd. for C14H19N3O5 : C, 54.36; H, 6.19; N, 13.58. Found: C, 54.47; H, 6.25; N, 13.37.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=O)[CH:5]=[N:6][CH:7]=1.[CH3:10][S:11]([NH2:14])(=[O:13])=[O:12].C(O)(=O)C.C(N(CC)CC)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][NH:14][S:11]([CH3:10])(=[O:13])=[O:12])[CH:5]=[N:6][CH:7]=1
Reactant: O=Cc1cncc(Br)c1
Reactant: CS(N)(=O)=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCN(CC)CC
Solvent: ClCCCl
Product: CS(=O)(=O)NCc1cncc(Br)c1
Reaction time: 8 h

Procedure:
To a solution of 5-bromo-3-pyridine-carboxaldehyde (1.5 g, 7.9 mmol), methanesulfonamide (0.5 g, 5.3 mmol), acetic acid (0.637 g, 10.6 mmol), triethylamine (1.07 g, 10.6 mmol) in DCE (50 mL) at ambient temperature is added NaBH(OAc)3 (3.14 g, 14.84 mmol). The reaction mixture is stirred overnight. Aqueous NaHCO3 (20 mL) is added and the organic phase is separated. The aqueous phase is extracted with dichloromethane and the combined organic phase is dried over Na2SO4. Concentration affords a residue which is purified by silica gel flash chromatography with a methanol in dichloromethane gradient to afford N-(5-bromo-pyridin-3-ylmethyl)-methanesulfonamide as a solid. MS (ESI) m/z 266.9 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([NH2:8])[N:5]=[C:4]([NH2:9])[CH:3]=1.C1(C)C=C(C)C=C(C)C=1S(O[NH2:22])(=O)=O.[O:24]1[CH:28]=[CH:27][CH:26]=[C:25]1[CH:29]=[CH:30][CH:31]=O>>[Br:1][C:2]1[CH:7]=[C:6]([NH2:8])[N:5]2[N:22]=[C:31]([CH:30]=[CH:29][C:25]3[O:24][CH:28]=[CH:27][CH:26]=3)[N:9]=[C:4]2[CH:3]=1
Reactant: Nc1cc(Br)cc(N)n1
Reactant: Cc1cc(C)c(S(=O)(=O)ON)c(C)c1
Reactant: O=CC=Cc1ccco1
Product: Nc1cc(Br)cc2nc(C=Cc3ccco3)nn12

Procedure:
The title compound, MS m/e (%): 305 (M+, 100), was prepared in accordance with the general method of example 63 from 4-bromo-pyridine-2,6-diamine, O-mesitylene-sulfonylhydroxylamine, and 3-(2-furyl)-acrolein. The purification was performed with reversed phase HPLC eluting with an acetonitrile/water gradient.
Reaction SMILES: [N:1]#[C:2][NH2:3].C(OC(=O)[N:10]([CH2:23][CH3:24])[CH2:11][CH2:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]=[C:21]=[S:22])=[CH:16][CH:15]=1)(C)(C)C.Br[CH2:27][C:28]([C:30]1[CH:31]=[CH:32][C:33]2[O:37][CH2:36][CH2:35][C:34]=2[CH:38]=1)=[O:29]>>[NH2:1][C:2]1[N:3]=[C:21]([NH:20][C:17]2[CH:16]=[CH:15][C:14]([O:13][CH2:12][CH2:11][NH:10][CH2:23][CH3:24])=[CH:19][CH:18]=2)[S:22][C:27]=1[C:28]([C:30]1[CH:31]=[CH:32][C:33]2[O:37][CH2:36][CH2:35][C:34]=2[CH:38]=1)=[O:29]
Reactant: N#CN
Reactant: CCN(CCOc1ccc(N=C=S)cc1)C(=O)OC(C)(C)C
Reactant: O=C(CBr)c1ccc2c(c1)CCO2
Product: CCNCCOc1ccc(Nc2nc(N)c(C(=O)c3ccc4c(c3)CCO4)s2)cc1

Procedure:
This compound was prepared from cyanamide, ethyl-[2-(4-isothiocyanato-phenoxy)-ethyl]-carbamic acid tert-butyl ester of Example 129 and 2-bromo-1-(2,3-dihydro-benzofuran-5-yl)ethanone (from Example 141) following a procedure similar to Example 132. Mass spectrum (ES) MH+=425.
Reaction SMILES: [CH:1]([O:4][C:5]1[N:10]=[CH:9][C:8]([O:11][C:12]2[S:13][C:14]([C:17]#[N:18])=[CH:15][N:16]=2)=[CH:7][CH:6]=1)([CH3:3])[CH3:2].C(N(CC)CC)C.Cl.[NH2:27][OH:28]>C(O)C.O>[OH:28][N:27]=[C:17]([C:14]1[S:13][C:12]([O:11][C:8]2[CH:9]=[N:10][C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[CH:6][CH:7]=2)=[N:16][CH:15]=1)[NH2:18]
Reactant: NO
Reactant: CC(C)Oc1ccc(Oc2ncc(C#N)s2)cn1
Agent: Cl
Solvent: CCO
Solvent: O
Solvent: CCN(CC)CC
Product: CC(C)Oc1ccc(Oc2ncc(C(N)=NO)s2)cn1
Yield: 97.2 %

Procedure:
To a solution of Example 81A (343 mg, 1.3 mmol) and triethylamine (0.9 ml, 6.5 mmol) in ethanol/water (95:5, v/v, 10 mL) was added hydroxylamine hydrochloride (228 mg, 3.25 mmol). The reaction was heated at reflux for 15 minutes and concentrated on a rotary evaporator. The residual solids were dissolved in dichloromethane (50 mL), and washed with water (50 mL) and brine (50 mL), dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash chromatography on silica gel eluting with a solvent gradient from 10% to 30% ethyl acetate in hexanes to provide 372 mg of the title compound (96%) as a off-white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.30 (d, J=6.25 Hz, 6H) 5.11-5.33 (m, 1H) 6.03 (s, 2H) 6.84 (d, J=9.19 Hz, 1H) 7.61 (s, 1H) 7.78 (dd, J=9.01, 3.13 Hz, 1H) 8.22 (d, J=2.94 Hz, 1H) 9.71 (s, 1H); MS (ESI) m/z 295.0 (M+H)+.