Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[O:9]=[C:10]1[N:18]2[C:19]([CH2:28][NH:29][C:30](=[O:32])[CH3:31])([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[CH2:20][O:21][C:16]3=[C:17]2[C:12](=[CH:13][CH:14]=[CH:15]3)[NH:11]1>C(#N)C.C(O)(=O)C>[Br:1][C:15]1[C:16]2[O:21][CH2:20][C:19]([CH2:28][NH:29][C:30](=[O:32])[CH3:31])([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=3)[N:18]3[C:10](=[O:9])[NH:11][C:12]([C:17]=23)=[CH:13][CH:14]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: CC(=O)NCC1(c2ccccn2)COc2cccc3[nH]c(=O)n1c23
Solvent: CC(=O)O
Solvent: CC#N
Product: CC(=O)NCC1(c2ccccn2)COc2c(Br)ccc3[nH]c(=O)n1c23
Temperature: 0 °C
Reaction time: 1 h
Yield: 60 %

Procedure:
N-Bromosuccinimide (40 mg, 0.2 mmol) was added to a mixture of N-[(2-oxo-4-pyridin-2-yl-1,2,4,5-tetrahydroimidazo[1,5,4-de][1,4]benzoxazin-4-yl)methyl]acetamide in acetonitrile (5 mL) and acetic acid (3 mL), and cooled to 0° C. The reaction was stirred for 1 h, concentrated to remove residual acetic acid, and partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and concentrated to give crude N-[(7-bromo-2-oxo-4-pyridin-2-yl-1,2,4,5-tetrahydroimidazo[1,5,4-de][1,4]benzoxazin-4-yl)methyl]acetamide (0.040 g. 60%). LCMS calculated for C17H16BrN4O3 (M+H)+: m/z=403.1, 405.1. found: 402.9, 405.0.
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[C:3]([NH:5][C:6]1[C:11]([S:12][CH3:13])=[CH:10][C:9]([CH3:14])=[CH:8][C:7]=1Br)=[O:4].C([Li])CCC.[C:23](=[O:25])=[O:24]>C(OCC)C.CCCCCC>[CH3:14][C:9]1[CH:10]=[C:11]([S:12][CH3:13])[C:6]([NH:5][C:3](=[O:4])[C:2]([F:17])([F:16])[F:1])=[C:7]([CH:8]=1)[C:23]([OH:25])=[O:24]
Reactant: O=C=O
Reactant: CSc1cc(C)cc(Br)c1NC(=O)C(F)(F)F
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: CCOCC
Product: CSc1cc(C)cc(C(=O)O)c1NC(=O)C(F)(F)F
Reaction time: 2 h
Yield: 74.4 %

Procedure:
Under an atmosphere of argon, 46.6 g (142 mmol) of N-(trifluoroacetyl)-2-bromo-4-methyl-6-(methylthio)aniline in 750 ml of dry diethyl ether were cooled to a temperature of −65° C. At this temperature, 119 ml of a 2.5M solution (297.5 mmol) of n-butyllithium in hexane were added dropwise. The mixture was subsequently stirred at this temperature for 2 h. The contents were then carefully poured onto a mixture of 62.5 g (1.42 mol) of carbon dioxide (as dry ice ground in a mortar) and 150 ml of dry ether. The mixture was thawed to RT and extracted three times with water. The combined aqueous phases were acidified to pH<2 with dilute hydrochloric acid and cooled to a temperature of 0° C.-5° C. The mixture was filtered, giving 31.0 g of 5-methyl-3-(methylthio)-2-(trifluoroacetylamino)benzoic acid as residue.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:9]=[CH:8][C:6]([NH2:7])=[CH:5][CH:4]=1.C(N(CC)CC)C.[Cl-].ClC1N(C)CC[NH+]1C.[CH3:26][O:27][C:28]1[C:29]([CH3:58])=[C:30]([C:49]([O:56][CH3:57])=[C:50]([O:54][CH3:55])[C:51]=1[O:52][CH3:53])[CH2:31][C:32]1[CH:33]=[CH:34][C:35]([O:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[C:36]([CH:40]=1)[C:37](O)=[O:38]>C(Cl)Cl>[CH3:26][O:27][C:28]1[C:29]([CH3:58])=[C:30]([C:49]([O:56][CH3:57])=[C:50]([O:54][CH3:55])[C:51]=1[O:52][CH3:53])[CH2:31][C:32]1[CH:33]=[CH:34][C:35]([O:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[C:36]([CH:40]=1)[C:37]([NH:7][C:6]1[CH:8]=[CH:9][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)=[O:38]
Reactant: COc1c(C)c(Cc2ccc(OCc3ccccc3)c(C(=O)O)c2)c(OC)c(OC)c1OC
Reactant: COc1ccc(N)cc1
Agent: CN1CC[NH+](C)C1Cl
Agent: [Cl-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc(NC(=O)c2cc(Cc3c(C)c(OC)c(OC)c(OC)c3OC)ccc2OCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 37.2 %

Procedure:
p-Methoxyaniline (0.250 g, 2.03 mmol), triethylamine (0.206 g, 2.03 mmol) and 2-chloro-1,3-dimethylimidazolinium chloride (0.344 g, 2.03 mmol) were added to a methylene chloride solution (40 ml) of 5-(3,4,5,6-tetramethoxy-2-methylbenzyl)-2-benzyloxybenzoic acid (0.460 g, 1.02 mmol) and the resulting solution was stirred at room temperature for 12 hours. The reaction solution was poured into ice water and then extracted with methylene chloride. The extract was washed with water and then dried, and the solvent was removed by distillation. The obtained residue was purified by preparative thin-layer chromatography (ethyl acetate:hexane=1:2) and recrystallized from ether to obtain the titled compound (0.211 g, 0.379 mmol, 37%).
Reaction SMILES: C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH2:15]([CH:17]([NH:20][CH2:21][CH2:22][NH:23][C:24](=[O:33])[O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:18][CH3:19])[CH3:16].[CH3:34][CH:35]([CH3:39])[CH2:36]C=O.C(O)(=O)C>ClCCl>[CH2:15]([CH:17]([N:20]([CH2:34][CH:35]([CH3:39])[CH3:36])[CH2:21][CH2:22][NH:23][C:24](=[O:33])[O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:18][CH3:19])[CH3:16]
Reactant: CCC(CC)NCCNC(=O)OCc1ccccc1
Reactant: CC(C)CC=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)O
Product: CCC(CC)N(CCNC(=O)OCc1ccccc1)CC(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 59.7 %

Procedure:
Sodium triacetoxyborohydride (1.87 g, 8.84 mmol) was added to a solution of benzyl 2-[(1-ethylpropyl)amino]ethylcarbamate (1.8 g, 6.8 mmol) (Preparation 50), 3-methylbutanal (0.8 ml, 7.5 mmol) and acetic acid (1 ml, 8.85 mmol) in dichloromethane (50 ml). The reaction mixture was stirred for 16 hours at room temperature. The reaction mixture was diluted with dichloromethane (50 ml) and then washed with saturated aqueous sodium hydrogen carbonate solution (100 ml). The organic phase was dried over anhydrous magnesium sulphate and then the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol (95:5 by volume) increasing in polarity to dichloromethane:methanol:0.88 concentrated aqueous ammonia (95:5:0.5 by volume). This gave the title compound as an oil (1.3 g).
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].Cl[C:11]1[N:16]=[C:15]([Cl:17])[CH:14]=[C:13]([Cl:18])[N:12]=1>O.CC(C)=O>[Cl:18][C:13]1[CH:14]=[C:15]([Cl:17])[N:16]=[C:11]([O:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:12]=1
Reactant: Clc1cc(Cl)nc(Cl)n1
Reactant: Oc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Solvent: O
Product: Clc1cc(Cl)nc(Oc2ccccc2)n1

Procedure:
Phenol (0.94 g, 10 mmol) and sodium hydroxide (0.44 g, 11 mmol) in water (20 ml) were added to 2,4,6-trichloropyrimidine (1.83 g, 10 mmol) in acetone (20 ml) at 0° C. The mixture was stirred over night. The precipitate then filtered through celite, then the most of the acetone was removed in vacuo. The resulting aqueous solution was extracted with ethyl acetate, dried over sodium sulfate, and concentrated in vacuo. The residue was purified in silica to provide a colorless oil.
Reaction SMILES: [CH3:1][N:2]1[C:7]([CH3:9])([CH3:8])[CH2:6][CH:5]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH:18]3[CH2:20][O:19]3)=[CH:12][CH:11]=2)[CH2:4][C:3]1([CH3:22])[CH3:21].[N:23]#[C:24][NH2:25].[Na]>>[CH3:1][N:2]1[C:3]([CH3:21])([CH3:22])[CH2:4][CH:5]([C:10]2[CH:11]=[CH:12][C:13]([O:16][CH2:17][CH:18]3[O:19][C:24]([NH2:25])=[N:23][CH2:20]3)=[CH:14][CH:15]=2)[CH2:6][C:7]1([CH3:8])[CH3:9]
Reactant: N#CN
Reactant: CN1C(C)(C)CC(c2ccc(OCC3CO3)cc2)CC1(C)C
Agent: [Na]
Product: CN1C(C)(C)CC(c2ccc(OCC3CN=C(N)O3)cc2)CC1(C)C

Procedure:
The title compound was prepared from 1,2,2,6,6-pentamethyl-4-(4-oxiranylmethoxy-phenyl)-piperidine and sodium hydrogen cyanamide according to the procedures employed for the preparation of the compound in Step 2 of Example 1.
Reaction SMILES: C([O:5][C:6](=[O:51])[CH:7]([NH:16][C:17](=[O:50])[CH:18]([CH2:42][C:43]([O:45]C(C)(C)C)=[O:44])[CH2:19][CH2:20][CH2:21][S:22]C(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[CH2:8][C:9]([O:11]C(C)(C)C)=[O:10])(C)(C)C.C(O)(C(F)(F)F)=O.C(S)(S)C.C([SiH](C(C)C)C(C)C)(C)C>C(Cl)Cl>[C:43]([CH2:42][CH:18]([CH2:19][CH2:20][CH2:21][SH:22])[C:17]([NH:16][CH:7]([CH2:8][C:9]([OH:11])=[O:10])[C:6]([OH:51])=[O:5])=[O:50])([OH:45])=[O:44]
Reactant: CC(C)(C)OC(=O)CC(CCCSC(c1ccccc1)(c1ccccc1)c1ccccc1)C(=O)NC(CC(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Agent: CC(C)[SiH](C(C)C)C(C)C
Agent: CC(S)S
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(O)CC(CCCS)C(=O)NC(CC(=O)O)C(=O)O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To the protected thiolate of Example 119 in CH2Cl2 (1 mL) was added at 0° C. a solution of 60% TFA in CH2Cl2, containing 2% of ethanedithiol. Triisopropyl silane (1%) was then added and the reaction mixture was stirred at room temperature for 1 hour after which it was first concentrated using a stream of argon and then under vacuum. The obtained white solid was washed several times with a mixture of diethyl ether/hexanes (3:1). The obtained white solid was purified by semi-preparative HPLC to provide the desired compound.
Reaction SMILES: [CH2:1]([N:3]1[CH2:20][CH:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:18][C:5]2([CH2:10][CH2:9][N:8](C(OC(C)(C)C)=O)[CH2:7][CH2:6]2)[CH2:4]1)[CH3:2].FC(F)(F)C(O)=O>C(Cl)Cl>[CH2:1]([N:3]1[CH2:20][CH:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:18][C:5]2([CH2:10][CH2:9][NH:8][CH2:7][CH2:6]2)[CH2:4]1)[CH3:2]
Reactant: CCN1CC(c2ccccc2)OC2(CCN(C(=O)OC(C)(C)C)CC2)C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCN1CC(c2ccccc2)OC2(CCNCC2)C1
Reaction time: 0.5 h
Yield: 99.9 %

Procedure:
To tert-butyl 8-ethyl-10-phenyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (540 mg, 1.50 mmol) in DCM (1.5 mL) was added 2,2,2-trifluoroacetic acid (1 mL, 12.98 mmol) and the solution was stirred for 30 minutes. The reaction mixture was concentrated in vacuo, diluted with DCM (50 mL), washed with 1:1 sat. aq. Na2CO3/NaHCO3 (10 ml) and the aqueous was extracted further with DCM (2×25 mL). The combined organics were dried (MgSO4) and evaporated to give 8-ethyl-10-phenyl-11-oxa-3,8-diazaspiro[5.5]undecane (390 mg, 100%) as a pale yellow solid, which was used without further purification. ESI-MS m/z calc. 260.4. found 261.3 (M+1)+; Retention time: 0.3 minutes (3 min run).
Reaction SMILES: [CH3:1][C:2]1[C:3]([C:12]([C:14]2[N:15]=[CH:16][N:17]([C:19]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:18]=2)=O)=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.C[Mg+].[Br-].[CH3:41]CN(CC)CC.CS(Cl)(=O)=O>C1COCC1.C(Cl)Cl>[CH3:1][C:2]1[C:3]([C:12]([C:14]2[N:15]=[CH:16][N:17]([C:19]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:18]=2)=[CH2:41])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2
Reactant: CCN(CC)CC
Reactant: Cc1c(C(=O)c2cn(C(c3ccccc3)(c3ccccc3)c3ccccc3)cn2)ccc2cccnc12
Agent: CS(=O)(=O)Cl
Agent: C[Mg+]
Agent: [Br-]
Solvent: C1CCOC1
Solvent: ClCCl
Product: C=C(c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1)c1ccc2cccnc2c1C
Yield: 59.8 %

Procedure:
A solution of (8-methylquinolin-7-yl)(1-trityl-1H-imidazol-4-yl)methanone (Intermediate M4) (3.59 g, 7.49 mmol) in THF (100 mL) at 0° C. was treated with MeMgBr (5.0 mL, 3M in ether) for 16 h. The reaction mixture was quenched with NH4Cl (aq) and extracted with EtOAc. The layers were separated and dried over MgSO4, filtered, evaporated and purified by column chromatography on silica gel with 3 to 4% NH3-MeOH. The alcohol in CH2Cl2 (100 mL) was treated with Et3N (8.4 mL, 60.3 mmol) and methane sulfonyl chloride (1.75 mL, 22.6 mmol) at 0° C. for 3 h. The mixture was quenched with water and extracted with CH2Cl2. The organic layers were pooled and evaporated to give 8-methyl-7-[1-(1-trityl-1H-imidazol-4-yl)vinyl]quinoline (Intermediate M5) 2.14 g (60% over two steps). This material was used in the next step without further purification.
Reaction SMILES: [CH3:1][S:2]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([CH2:23][CH2:24][CH2:25][CH2:26][S:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)(=[N:14][CH2:15][CH2:16][N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[O:13])=[CH:8][CH:7]=1)(=[O:4])=[O:3].S(=O)(=O)(O)[OH:35].B1([O-])OO1.O.O.O.O.[Na+]>CO>[N:17]1([CH2:16][CH2:15][N:14]=[S:12]([C:9]2[CH:8]=[CH:7][C:6]([NH:5][S:2]([CH3:1])(=[O:3])=[O:4])=[CH:11][CH:10]=2)([CH2:23][CH2:24][CH2:25][CH2:26][S:27]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[O:35])=[O:13])[CH2:18][CH2:19][O:20][CH2:21][CH2:22]1
Reactant: CS(=O)(=O)Nc1ccc(S(=O)(CCCCSc2ccccc2)=NCCN2CCOCC2)cc1
Reactant: O=S(=O)(O)O
Agent: [Na+]
Agent: [O-]B1OO1
Solvent: O
Solvent: CO
Product: CS(=O)(=O)Nc1ccc(S(=O)(CCCCS(=O)c2ccccc2)=NCCN2CCOCC2)cc1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
A cold (0° C.) solution of S-[4-(methanesulfonylamino)phenyl]-N-[2-(4-morpholinyl)ethyl]-S-[4-(phenylthio)butyl]sulfoximine in methanol is treated slowly with excess 30% sulfuric acid and then sodium perborate tetrahydrate (10 equivalents) is added. The mixture is stirred at 0° C. for 2 hrs and then at ambient temperature for 2 hrs. The methanol is removed in vacuo and the residue basified with 50% sodium hydroxide and filtered. The filter cake is washed with methylene chloride. The aqueous filtrate is extracted with methylene chloride and the extract combined with the methylene chloride used to wash the filter cake. The methylene chloride solution is washed with water, dried and concentrated to obtain the title compound.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([NH:8][CH:9]=O)[N:3]=1.Cl[CH2:12]C=O.Cl.C(OCC)(=O)C>C(O)C>[F:1][C:2]1[N:3]2[CH:12]=[CH:9][N:8]=[C:4]2[CH:5]=[CH:6][CH:7]=1
Reactant: O=CNc1cccc(F)n1
Reactant: O=CCCl
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CCO
Product: Fc1cccc2nccn12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
2-Fluoro-6-formylaminopyridine (5 g) was dissolved in 50 mL of ethanol. To the solution was added 23.5 mL (4 equivalents) of 40% chloroacetaldehyde. The mixture was stirred for one hour under reflux. The reaction mixture was gradually cooled to room temperature, to which were added a 1N—HCl aqueous solution (100 mL) and ethyl acetate (100 mL). The ethyl acetate solution was subjected to extraction with a 1N—HCl aqueous solution (100 mL×2). The aqueous solutions were combined, to which was added NaHCO3 for neutralization (pH 0.35-7.30). To the neutralized aqueous solution was added ethyl acetate (100 mL×3) to extract the product. The extract solutions were combined and dried over magnesium sulfate, which was concentrated under reduced pressure to afford 5-fluoroimidazo[1,2-a]pyridine as a black liquid product (1.5 g, yield 31%).
Reaction SMILES: [C:1]([C:4]1[CH:9]=[C:8]([Cl:10])[C:7]([Cl:11])=[CH:6][C:5]=1[NH:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])(=[O:3])[NH2:2].[O:19]1CCOC[CH2:20]1>>[Cl:10][C:8]1[CH:9]=[C:4]2[C:5](=[CH:6][C:7]=1[Cl:11])[N:12]([CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:20](=[O:19])[NH:2][C:1]2=[O:3]
Reactant: CCOC(=O)CNc1cc(Cl)c(Cl)cc1C(N)=O
Reactant: C1COCCO1
Product: CCOC(=O)Cn1c(=O)[nH]c(=O)c2cc(Cl)c(Cl)cc21
Temperature: 140 °C
Reaction time: 0.5 h

Procedure:
Ethyl N-(2-carbamoyl-4,5-dichlorophenyl)aminoacetate (4.6 g) and N,N'-carbonyldiimidazole (5.12 g) were dissolved in dioxane (50 ml). The solution was evaporated to give a residue, which was stirred at 140° C. for 30 minutes. After cooling, the precipitates were collected by filtration and washed with ethanol to give ethyl 2-(6,7-dichloro-1,2,3,4-tetrahydro-2,4-dioxoquinazolin-1-yl)acetate (4.40 g).
Reaction SMILES: C([O:4][C@@H:5]1[C@@H:10]([O:11]C(=O)C)[C@H:9]([O:15]C(=O)C)[C@@H:8]([CH2:19][O:20]C(=O)C)[O:7][C@H:6]1[C:24]1[C:32]2[C:27](=[C:28]([Cl:33])[CH:29]=[CH:30][CH:31]=2)[N:26]([CH2:34][C:35]2[CH:40]=[CH:39][C:38]([O:41][CH2:42][CH2:43]OS(C)(=O)=O)=[CH:37][CH:36]=2)[CH:25]=1)(=O)C.[N-:49]=[N+]=[N-].[Na+].O>CN(C)C=O>[NH2:49][CH2:43][CH2:42][O:41][C:38]1[CH:37]=[CH:36][C:35]([CH2:34][N:26]2[C:27]3[C:32](=[CH:31][CH:30]=[CH:29][C:28]=3[Cl:33])[C:24]([C@@H:6]3[O:7][C@H:8]([CH2:19][OH:20])[C@@H:9]([OH:15])[C@H:10]([OH:11])[C@H:5]3[OH:4])=[CH:25]2)=[CH:40][CH:39]=1
Reactant: CC(=O)OC[C@H]1O[C@@H](c2cn(Cc3ccc(OCCOS(C)(=O)=O)cc3)c3c(Cl)cccc23)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: NCCOc1ccc(Cn2cc([C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)c3cccc(Cl)c32)cc1
Temperature: 100 °C
Reaction time: 2 h
Yield: 21.7 %

Procedure:
To a solution of 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-7-chloro-1-{4-[2-(methanesulfonyloxy)ethoxy]-benzyl}-1H-indole (85 mg) in N,N-dimethylformamide (2 mL) was added sodium azide (12 mg), and the mixture was stirred at 100° C. for 2 hours. The reaction mixture was poured into water, and the resulting mixture was extracted with diethyl ether. The extract was washed with water and brine successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue was dissolved in a mixed solvent of methanol (2 mL) and tetra hydrofuran (3 mL). To the solution was added sodium methoxide (28% methanol solution, 0.30 mL), and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, and the resulting mixture was extracted with ethylacetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue was dissolved in tetra hydrofuran (3 mL). To the solution were added water (0.3 mL) and triphenylphosphine (36 mg), and the mixture was stirred at room temperature for 3 days. The solvent was removed under reduced pressure, and the residue was purified by preparative reverse phase column chromatography (Shiseido CAPCELL PAK C18 ODS, UG80, 5 μm, 20×50 mm, linear gradient water/methanol=90/10-10/90, flow rate 30 mL/min) to give the title compound (12 mg).
Reaction SMILES: [CH:1]12[C:11]3([Cl:15])[C:12]([Cl:14])([Cl:13])[C:8]([Cl:18])([C:9]([Cl:17])=[C:10]3[Cl:16])[CH:2]1[C:3]([O:5][C:6]2=[O:7])=O.C1(C)C=CC=CC=1.[SH:26][C:27]1[CH:33]=[CH:32][CH:31]=[CH:30][C:28]=1[NH2:29]>O>[SH:26][C:27]1[CH:33]=[CH:32][CH:31]=[CH:30][C:28]=1[N:29]1[C:6](=[O:7])[CH:1]2[CH:2]([C:8]3([Cl:18])[C:12]([Cl:13])([Cl:14])[C:11]2([Cl:15])[C:10]([Cl:16])=[C:9]3[Cl:17])[C:3]1=[O:5]
Reactant: O=C1OC(=O)C2C1C1(Cl)C(Cl)=C(Cl)C2(Cl)C1(Cl)Cl
Reactant: Nc1ccccc1S
Solvent: Cc1ccccc1
Solvent: O
Product: O=C1C2C(C(=O)N1c1ccccc1S)C1(Cl)C(Cl)=C(Cl)C2(Cl)C1(Cl)Cl

Procedure:
A 3000 ml 3-neck round bottom flask, equipped with a Dean-Stark water trap and a mechanical stirrer, was charged with 203.5 g (10% molar excess) of chlorendic anhydride and 1600 ml of toluene. Sixty-two grams of 2-mercaptoaniline was added to the resultant solution, whereupon a pale yellow suspension was formed. The reaction mixture was heated gradually until the solvent began to reflux and the evolution of water commenced and it was collected in the Dean-Stark water trap. The heating and refluxing were continued until the calculated amount of water, 9 ml. was collected, this requiring a total of 6 hours. At this point, there was no solid left in the reaction mixture. Solvent was then distilled to reduce the volume to about one-half. The residue, a clear solution, was then poured into 1000 ml of Skellysolve B (a mixture of hexanes, b. pt. = 146°-156° F., from Skelly Oil Co.) and the resultant solid was separated by filtration on a Buchner funnel and dried in air overnight. One crystallization from toluene gave white crystals of the dicarboximide with a melting point of 195°-8° C.
Reaction SMILES: [Br:1]Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:22]([N:41]1[C:45]([CH2:46][CH2:47][CH2:48]O)=[N:44][CH:43]=[N:42]1)([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N(CC)CC)C>ClCCl>[Br:1][CH2:48][CH2:47][CH2:46][C:45]1[N:41]([C:22]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:42]=[CH:43][N:44]=1
Reactant: BrBr
Reactant: OCCCc1ncnn1C(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: BrCCCc1ncnn1C(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: -5 °C
Yield: 43.3 %

Procedure:
A solution of bromine (5.6 g) in dichloromethane (15 ml) was added dropwise to a stirred solution of triphenylphosphine (9.2 g) in dichloromethane (100 ml) cooled to -5° C. The mixture was stirred for a further ten minutes at 0° C., then treated portionwise with a solution of the above alcohol (6.9 g) and triethylamine (4.9 ml) in dichloromethane (30 ml) again maintaining the temperature below 0° C. The solution was stirred for a further ten minutes, filtered through a bed of silica, then chromatographed on silica, using dichloromethane-ether (25:1) as eluant, to give 1-bromo-3(1-trityl-1,2,4-triazol-5-yl)propane (3.5 g, m.p. 146°-149° C.). NMR (CDCl3): δ1.8(2H,m), 2.15(2H,t), 3.2(2H,t), 7.1-7.3(15H,m), 7.9(1H,s). 13C NMR was used to confirm the position of the trityl substituent.
Reaction SMILES: C1C=C[NH+]=CC=1.[O-:7][Cr](Cl)(=O)=O.[CH3:12][S:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2(O)[CH2:24][CH2:23][CH:22]=[C:21]2[C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)=[CH:16][CH:15]=1>C(Cl)Cl.CCOCC>[F:31][C:28]1[CH:29]=[CH:30][C:25]([C:21]2[C:22](=[O:7])[CH2:23][CH2:24][C:20]=2[C:17]2[CH:18]=[CH:19][C:14]([S:13][CH3:12])=[CH:15][CH:16]=2)=[CH:26][CH:27]=1
Reactant: CSc1ccc(C2(O)CCC=C2c2ccc(F)cc2)cc1
Reactant: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Solvent: CCOCC
Product: CSc1ccc(C2=C(c3ccc(F)cc3)C(=O)CC2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 68.9 %

Procedure:
To a suspension of PCC (4.5 g, 20.9 mmol) and 10 g of anhydrous 4 Å molecular sieves in 150 mL of CH2Cl2 was added a solution of 2.2 g (7.3 mmol) of 1-(4-(methylthio)phenyl)-2-(4-fluorophenyl)-2-cyclopenten-1-ol in 20 mL CH2Cl2. The mixture was stirred for 1 h at r.t. and then diluted with 300 mL of Et2O. After filtration and concentration, the residue was flash chromatographed with 2:1 hexane/EtOAc to give 1.5 g of the title product.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:13]([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH3:13][N:10]1[C:11]2[C:7](=[CH:6][CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:12]=2)[CH:8]=[CH:9]1
Reactant: O=[N+]([O-])c1ccc2cc[nH]c2c1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cn1ccc2ccc([N+](=O)[O-])cc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 97.6 %

Procedure:
To a solution of 6-nitroindole (4.05 g 25 mmol) in DMF (50 mL) was added K2CO3 (8.63 g, 62.5 mmol) and Me (5.33 g, 37.5 mmol). After stirring at room temperature overnight, the mixture was poured into water and extracted with ethyl acetate. The combined organic layers were dried over Na2SO4 and concentrated under vacuum to give the product 1-methyl-6-nitro-1H-indole (4.3 g, 98%).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[CH3:12][C:13]([CH3:18])([CH3:17])[CH2:14][CH:15]=O.N1CCCC1>CO>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5](/[C:6](=[CH:15]/[CH2:14][C:13]([CH3:18])([CH3:17])[CH3:12])/[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1
Reactant: CC(C)(C)CC=O
Reactant: O=C1Cc2ccc(Cl)cc2N1
Solvent: CO
Solvent: C1CCNC1
Product: CC(C)(C)C/C=C1\C(=O)Nc2cc(Cl)ccc21
Temperature: 100 °C
Yield: 99.4 %

Procedure:
To the mixture of 6-chlorooxindole (0.26 g, 1.49 mmol) (Crescent) and 3,3-dimethyl-butyraldehyde (0.21 g, 2.09 mmol) (Aldrich) in methanol (20 mL) was added pyrrolidine (0.15 g, 2.09 mmol) (Aldrich) dropwise. The mixture was then heated at 100° C. for 1 h. The mixture was concentrated, and the residue was partitioned between ethyl acetate and water. The organic layer was separated, dried over Na2SO4, concentrated, and dried in vacuo to give the crude E/Z-6-chloro-3-(3,3-dimethyl-butylidene)-1,3-dihydro-indol-2-one as a white solid (Yield 0.37 g, 100%).