Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[CH3:2][NH:3][CH2:4][C:5]#[N:6].[OH-].[Na+].O.[O:10]([C:17]1[CH:25]=[CH:24][CH:23]=[CH:22][C:18]=1[C:19](Cl)=[O:20])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C(Cl)Cl>[C:5]([CH2:4][N:3]([CH3:2])[C:19](=[O:20])[C:18]1[CH:22]=[CH:23][CH:24]=[CH:25][C:17]=1[O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)#[N:6]
Reactant: CNCC#N
Reactant: O=C(Cl)c1ccccc1Oc1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Product: CN(CC#N)C(=O)c1ccccc1Oc1ccccc1
Reaction time: 5 h

Procedure:
2.7 parts of methylaminoacetonitrile hydrochloride was added to a solution of 2 parts of sodium hydroxide in 25 parts of water at ~15°. When the addition was complete a solution of 5.8 parts of 2-phenoxybenzoyl chloride in 50 parts of methylene chloride was added dropwise. The mixture was stirred vigorously for 5 hrs. at ~20°. The methylene chloride layer was then separated, washed with water and dried over magnesium sulfate. Removal of the magnesium sulfate by filtration and concentration of the filtrate gave 4.6 parts of N-cyanomethyl-N-methyl-2-phenoxybenzamide as a viscous oil. NMR (CDCl3) 3δ(S,3H,CH3), 4.1δ,4.3δ (2S,2H,CH2), 7.05δ, (m,9H,Aromatic H).
Reaction SMILES: C([Al](CC(C)C)CC(C)C)C(C)C.CC(O)C.[Cl:18][C:19]1[CH:20]=[C:21]([CH:26]=[CH:27][CH:28]=1)[C:22](=[O:25])[CH2:23][Cl:24].Cl>C1(C)C=CC=CC=1.C1C=C2C=CC(O)=C(C3C4C(=CC=CC=4)C=CC=3O)C2=CC=1.O.CCCCCC>[Cl:24][CH2:23][C@H:22]([C:21]1[CH:26]=[CH:27][CH:28]=[C:19]([Cl:18])[CH:20]=1)[OH:25]
Reactant: O=C(CCl)c1cccc(Cl)c1
Agent: CC(C)C[Al](CC(C)C)CC(C)C
Agent: Cl
Agent: Oc1ccc2ccccc2c1-c1c(O)ccc2ccccc12
Solvent: CC(C)O
Solvent: O
Solvent: Cc1ccccc1
Product: O[C@H](CCl)c1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 126.9 %

Procedure:
To a slurry solution of 143 mg (0.5 mmol) of (R)-1,1′-bi-2-naphthol in 10 ml of toluene was added 0.5 ml (0.5 mmol) of a 1.0 M hexane solution of triisobutylaluminum at room temperature, and the mixture was stirred at room temperature for 30 minutes. Thereto 1.52 ml (20 mmol) of 2-propanol was added and the mixture was stirred further at room temperature for 30 minutes. Thereto 1.89 g (10 mmol) of m-chlorophenacyl chloride was added and the mixture was stirred further at 50° C. for 4 hours. To the mixture were added 2 ml of 1N hydrochloric acid and 20 ml of water to conduct hydrolysis. The mixture was extracted with ethyl acetate and concentrated to obtain 2.424 g of an oily product. The obtained oil was analyzed by HPLC.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH:14]2[CH2:15][O:16][CH2:17][CH:9]1[CH2:10][NH:11][C:12](=[O:18])[CH2:13]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:20]1[CH:21]=[CH:22][C:23]([N+:26]([O-:28])=[O:27])=[N:24][CH:25]=1>>[C:1]([O:5][C:6]([N:8]1[CH:14]2[CH2:15][O:16][CH2:17][CH:9]1[CH2:10][N:11]([C:20]1[CH:25]=[N:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=1)[C:12](=[O:18])[CH2:13]2)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1C2CNC(=O)CC1COC2
Reactant: O=[N+]([O-])c1ccc(Br)cn1
Product: CC(C)(C)OC(=O)N1C2COCC1CN(c1ccc([N+](=O)[O-])nc1)C(=O)C2
Yield: 60.2 %

Procedure:
Following general N—C coupling procedure 1, 4-Oxo-8-oxa-3,10-diaza-bicyclo[4.3.1]decane-10-carboxylic acid tert-butyl ester (0.776 g, 3.03 mmol) was combined with 5-Bromo-2-nitro-pyridine (0.676 g, 3.33 mmol) which gave 3-(6-Nitro-pyridin-3-yl)-4-oxo-8-oxa-3,10-diaza-bicyclo[4.3.1]decane-10-carboxylic acid tert-butyl ester (0.69 g, 1.732) in 57.2 yield. MS m/z 379.4 (M+H)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[N:6]=[C:5]([O:11][C:12]2[CH:20]=[CH:19][C:18]3[NH:17][C:16]([CH3:21])=[CH:15][C:14]=3[C:13]=2[C:22]([O:24][CH2:25][CH:26]=[CH2:27])=[O:23])[N:4]=1.S1(CCCC1)(=O)=O.F[B-](F)(F)F.[O:40]=[N+:41]=[O:42].N>C(#N)C>[CH3:10][O:9][C:7]1[CH:8]=[C:3]([O:2][CH3:1])[N:4]=[C:5]([O:11][C:12]2[CH:20]=[CH:19][C:18]3[NH:17][C:16]([CH3:21])=[C:15]([N+:41]([O-:42])=[O:40])[C:14]=3[C:13]=2[C:22]([O:24][CH2:25][CH:26]=[CH2:27])=[O:23])[N:6]=1
Reactant: C=CCOC(=O)c1c(Oc2nc(OC)cc(OC)n2)ccc2[nH]c(C)cc12
Reactant: O=[N+]=O
Agent: F[B-](F)(F)F
Agent: N
Solvent: CC#N
Solvent: O=S1(=O)CCCC1
Product: C=CCOC(=O)c1c(Oc2nc(OC)cc(OC)n2)ccc2[nH]c(C)c([N+](=O)[O-])c12
Temperature: -30 °C
Reaction time: 5 h
Yield: 55 %

Procedure:
2.0 g of allyl 5-[(4,6-dimethoxypyrimidin-2-yl)oxy]-2-methylindol-4-carboxylate was dissolved in 25 ml of acetonitrile, and the solution was cooled to -30° C. 16.3 ml of a 0.5M sulfolane solution of nitronium tetrafluoroborate was dropwise added thereto, and the mixture was stirred for 5 hours. After adding 2 ml of aqueous ammonia, the mixture was returned to room temperature and extracted with ethyl acetate. The organic layer was washed with water and then dried over anhydrous sodium sulfate. Crystals obtained by concentration under reduced pressure, were washed with hexane to obtain 1.23 g (yield: 55%) of the desired compound.
Reaction SMILES: Cl.[CH3:2][N:3]([CH3:11])[C:4](=[O:10])[C@@H:5]1[CH2:9][CH2:8][CH2:7][NH:6]1.C(N(CC)CC)C.S=[C:20]1[CH2:24][S:23][C:22](=[O:25])[NH:21]1>C(O)C>[CH3:2][N:3]([CH3:11])[C:4](=[O:10])[C@@H:5]1[CH2:9][CH2:8][CH2:7][N:6]1[C:20]1[CH2:24][S:23][C:22](=[O:25])[N:21]=1
Reactant: O=C1NC(=S)CS1
Reactant: CN(C)C(=O)[C@@H]1CCCN1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: CN(C)C(=O)[C@@H]1CCCN1C1=NC(=O)SC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of the crude product containing N,N-dimethyl-L-prolinamide hydrochloride obtained in B) (10.5 g) and triethylamine (13.6 g) in ethanol (100 mL) was added 4-thioxothiazolidin-2-one (6.0 g) at room temperature. The reaction mixture was stirred at room temperature for 3 hr, and the solvent was evaporated under reduced pressure. The obtained solid was suspended in THF, and the suspension was filtered through celite pad and silica gel pad. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (NH, ethyl acetate) to give the title compound (4.3 g).
Reaction SMILES: [N:1]1([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][OH:16])=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[CH3:24][S:25](Cl)(=[O:27])=[O:26]>ClCCl>[N:1]1([CH2:7][C:8]2[CH:9]=[CH:10][C:11]([CH2:14][CH2:15][O:16][S:25]([CH3:24])(=[O:27])=[O:26])=[CH:12][CH:13]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: OCCc1ccc(CN2CCCCC2)cc1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCCc1ccc(CN2CCCCC2)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A stirred solution of 2-(4-piperidin-1-ylmethylphenyl)ethanol (125 mg) and triethylamine (0.18 mL) in dichloromethane (5 mL) was treated dropwise at 0° C. with methanesulphonyl chloride (71.8 mg, 0.05 mL) and then stirred at room temperature for 3 hours. The mixture was diluted with methylene chloride and washed with water. The dried (sodium sulphate) organic layer was evaporated to give the subtitle compound as a water-white oil (150 mg).
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][C:26]4[O:27][CH:28]=[CH:29][CH:30]=4)[CH2:23][CH2:22][C:21]([C:31]([O:33]C)=[O:32])=[CH:20][C:19]=3[CH:35]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].[OH-].[Na+].O.Cl>O1CCCC1.CO>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][C:26]4[O:27][CH:28]=[CH:29][CH:30]=4)[CH2:23][CH2:22][C:21]([C:31]([OH:33])=[O:32])=[CH:20][C:19]=3[CH:35]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)OC)CCN3Cc2ccco2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)O)CCN3Cc2ccco2)cc1
Temperature: 25 °C
Reaction time: 120 h
Yield: 82.7 %

Procedure:
To a solution of methyl 7-(4-butoxyethoxyphenyl)-1-(2-furylmethyl)-2,3-dihydro-1-benzazepine-4-carboxylate (319 mg) in a mixture of tetrahydrofuran (21 ml) and methanol (21 ml) was added 1N sodium hydroxide solution (7 ml), and the mixture was stirred at room temperature for 5 days. Then, to the mixture was added water at 0° C., and 1N hydrochloric acid was further added to neutral, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with magnesium sulfate. The solvent was evaporated under reduced pressure, which was recrystallized from hexane-ethyl acetate to give 7-(4-butoxyethoxyphenyl)-1-(2-furylmethyl)-2,3-dihydro-1-benzazepine-4-carboxylic acid (256 mg) as yellow crystals.
Reaction SMILES: Br[C:2]1[N:7]2[N:8]=[C:9]([NH2:11])[N:10]=[C:6]2[CH:5]=[C:4]([CH3:12])[CH:3]=1.[O:13]1[C:18]2[CH:19]=[CH:20][C:21](B(O)O)=[CH:22][C:17]=2[O:16][CH2:15][CH2:14]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC(N(C)C)=O>O>[O:13]1[C:18]2[CH:19]=[CH:20][C:21]([C:2]3[N:7]4[N:8]=[C:9]([NH2:11])[N:10]=[C:6]4[CH:5]=[C:4]([CH3:12])[CH:3]=3)=[CH:22][C:17]=2[O:16][CH2:15][CH2:14]1
Reactant: OB(O)c1ccc2c(c1)OCCO2
Reactant: Cc1cc(Br)n2nc(N)nc2c1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(=O)N(C)C
Product: Cc1cc(-c2ccc3c(c2)OCCO3)n2nc(N)nc2c1
Temperature: 150 °C

Procedure:
5-Bromo-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (0.19 g, 0.84 mmol), 1,4-benzodioxane-6-boronic acid (0.18 g, 1.00 mmol), palladium(tetrakis)triphenylphosphine (97 mg, 0.084 mmol), potassium phosphate (0.36 g, 1.67 mmol), dimethylacetamide (3 ml) and water (1 ml) were added to a microwave vial containing a stirrer bar. The reaction was heated to 150° C. for 10 min. Water was added to the reaction mixture and the product extracted into ethyl acetate (×2). The organics were combined, washed several times with brine, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was triturated with diethyl ether and collected by filtration to give the desired product. LCMS RT: 2.82 min, MI: 283.17, Method: 2
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[ClH:7].[C:8]([NH:27][C@H:28]([C:36](O)=[O:37])[CH2:29][CH2:30][CH2:31][NH:32][C:33](=[NH:35])[NH2:34])([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>O1CCCC1>[ClH:7].[C:8]([NH:27][C@H:28]([CH2:36][OH:37])[CH2:29][CH2:30][CH2:31][NH:32][C:33](=[NH:34])[NH2:35])([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: N=C(N)NCCC[C@H](NC(c1ccccc1)(c1ccccc1)c1ccccc1)C(=O)O
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: C1CCOC1
Product: N=C(N)NCCC[C@@H](CO)NC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
4.2 g of lithium aluminum hydride were suspended in 150 ml of absolute tetrahydrofuran and cooled to 0° C. in an ice bath. 9.3 g of the methyl ester of tritylarginine hydrochloride, which were dissolved in 50 ml of absolute tetrahydrofuran, were slowly added dropwise to this suspension. The mixture was stirred at 0° C. for 30 min and then heated to 40°-45° C. After 30 min, the excess lithium aluminum hydride was decomposed with ice-water. Insolubles were removed by filtration, and the tetrahydrofuran was substantially removed by evaporation. The residue was neutralised with 0.1 N hydrochloric acid, taken up in n-butanol/ethyl acetate (1:1 parts by volume) and the solution was washed with water. After removal of the organic solvent by evaporation, tritylargininol hydrochloride was obtained in the form of a foam.
Reaction SMILES: [Si]([O:8][C:9]1[C:18]([CH3:19])=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:10]=1[CH2:20][CH2:21][OH:22])(C(C)(C)C)(C)C.[C:23](=O)(O)[O-].[Na+].O(C)S(C(F)(F)F)(=O)=O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>ClCCl.C(OCC)(=O)C>[OH:8][C:9]1[C:18]([CH3:19])=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:10]=1[CH2:20][CH2:21][O:22][CH3:23]
Reactant: COC(=O)c1cc(C)c(O[Si](C)(C)C(C)(C)C)c(CCO)c1
Reactant: O=C([O-])O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: COS(=O)(=O)C(F)(F)F
Agent: [F-]
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: COCCc1cc(C(=O)OC)cc(C)c1O
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of methyl 4-(tert-butyldimethylsilyloxy)-3-(2-hydroxyethyl)-5-methylbenzoate (48 mg, 0.148 mmol) in dichloromethane (3 mL) was treated with sodium bicarbonate (60 mg, 4 equivalents) and methyl triflate (68 uL, 4 equivalents). the reaction was stirred at room temperature for 16 h by which time TLC analysis indicated ˜50% conversion. The reaction was then diluted with ethyl acetate (20 mL) and filtered. The filtrate was evaporated to dryness. The residue was dissolved in THF (5 mL) and tetrabutylammonium fluoride (60 mg, 1.5 equivalents) was added. The reaction was stirred at room temperature. after 5 minutes, TLC analysis indicated complete conversion. The solvent was removed under educed pressure and the residue was dissolved in ethyl acetate (1 mL) and purified by preparative TLC on silica using 25% ethyl acetate/hexanes. Yield=13 mg (40%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][NH2:10])=[CH:5][CH:4]=1.[N+:11]([C:14]1[CH:19]=[CH:18][C:17]([N:20]2[CH2:25][CH2:24][CH:23]([C:26](=[O:31])C(Cl)(Cl)Cl)[C:22](=O)[C:21]2=[O:33])=[CH:16][CH:15]=1)([O-:13])=[O:12]>CO.C(O)(=O)C>[OH:31][C:26]1[C:23]2[CH2:24][CH2:25][N:20]([C:17]3[CH:18]=[CH:19][C:14]([N+:11]([O-:13])=[O:12])=[CH:15][CH:16]=3)[C:21](=[O:33])[C:22]=2[N:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[N:10]=1
Reactant: O=C1C(=O)N(c2ccc([N+](=O)[O-])cc2)CCC1C(=O)C(Cl)(Cl)Cl
Reactant: COc1ccc(NN)cc1
Solvent: CC(=O)O
Solvent: CO
Product: COc1ccc(-n2nc(O)c3c2C(=O)N(c2ccc([N+](=O)[O-])cc2)CC3)cc1

Procedure:
Condensation of 4-methoxyphenylhydrazine with 1-(4-nitro-phenyl)-4-(2,2,2-trichloro-acetyl)-piperidine-2,3-dione in refluxing methanol-acetic acid media afforded 3-hydroxy-1-(4-methoxy-phenyl)-6-(4-nitro-phenyl)-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one. Treatment of this intermediate with NaH and isopropyliodide afforded the corresponding 3-isopropoxy pyrazolo intermediate which was subjected to the same experimental protocol as described for Example 3 to afford the title compound. ESI mass spectrum 460 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:14]=[C:13]2[C:5]([C:6]3[CH:7]=[C:8]([Br:18])[CH:9]=[C:10]([C:15]([NH2:17])=[O:16])[C:11]=3[NH:12]2)=[CH:4][CH:3]=1.C([O-])(=O)C.[K+].C(OC)(OC)OC.O=[CH:32][CH2:33][N:34]([CH2:42][CH:43]=O)[C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38].C([BH3-])#N.[Na+]>CO.C1COCC1.C(Cl)Cl>[Br:18][C:8]1[CH:7]=[C:6]2[C:11](=[C:10]([C:15](=[O:16])[NH2:17])[CH:9]=1)[NH:12][C:13]1[CH:14]=[C:2]([N:1]3[CH2:43][CH2:42][N:34]([C:35]([O:36][C:37]([CH3:39])([CH3:38])[CH3:40])=[O:41])[CH2:33][CH2:32]3)[CH:3]=[CH:4][C:5]2=1
Reactant: CC(C)(C)OC(=O)N(CC=O)CC=O
Reactant: NC(=O)c1cc(Br)cc2c1[nH]c1cc(N)ccc12
Agent: CC(=O)[O-]
Agent: [BH3-]C#N
Agent: [K+]
Solvent: COC(OC)OC
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCN(c2ccc3c(c2)[nH]c2c(C(N)=O)cc(Br)cc23)CC1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 80.7 %

Procedure:
7-Amino-3-bromo-9H-carbazole-1-carboxamide (0.78 g, 1.282 mmol, Example 480B) was dissolved in methanol (40 mL)+THF (20.0 ml). potassium acetate (0.126 g, 1.282 mmol) acetate was added until pH ˜4-5. Trimethyl orthoformate (6 ml, 54 mmol) was added, followed by a solution of ˜2.9 mmol of tert-butyl bis(2-oxoethyl)carbamate in 10 ml CH2Cl2 (Example 409A). The reaction mixture was stirred at room temperature for 5 minutes, then sodium cyanoborohydride (503 mg, 8 mmol) was added and the mixture stirred at room temperature for 18 hours. The reaction mixture was partitioned between ethyl acetate and diluted aqueous NaHCO3 solution (500 ml water+25 ml saturated solution). The aqueous layer was extracted once more with ethyl acetate. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuum. The crude product was dissolved in MeOH+DCM, filtered through a Strata X-C strong cation exchange cartridge (2×5 g adsorbent). The cartridge was washed with methanol and the product eluted with 1+1 mixture of 2M NH3 in MeOH and DCM to give 0.49 g tert-butyl 4-(6-bromo-8-carbamoyl-9H-carbazol-2-yl)piperazine-1-carboxylate. Estimated purity ˜50%. The material was used “as is” in the next reaction. MS (ESI) m/e+=473/475 (1 Br isotope pattern).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[CH:7][CH:8]=[CH:9][C:2]1=2.[Li]C(C)(C)C.[CH3:15][N:16]([CH3:25])[C:17]1[CH:24]=[CH:23][C:20]([CH:21]=[O:22])=[CH:19][CH:18]=1>C1COCC1>[S:1]1[C:5]([CH:21]([OH:22])[C:20]2[CH:19]=[CH:18][C:17]([N:16]([CH3:15])[CH3:25])=[CH:24][CH:23]=2)=[CH:4][C:3]2[CH:6]=[CH:7][CH:8]=[CH:9][C:2]1=2
Reactant: c1ccc2sccc2c1
Reactant: CN(C)c1ccc(C=O)cc1
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Product: CN(C)c1ccc(C(O)c2cc3ccccc3s2)cc1

Procedure:
α-(2-benzo[b]thienyl)-4-dimethylaminobenzyl alcohol was prepared by the method of Example 40A with benzo[b]thiophene (7.5 mmoles, 1.0 g), t-BuLi(1.7M, 8.9 mmoles, 5.3 ml), 4-dimethylaminobenzaldehyde (8.9 mmoles, 1.3 g) and THF (20 ml). The crude product (2.4 g) was carried forward without further purification.
Reaction SMILES: [OH-].[Na+].C[O:4][C:5]([C:7]1[CH:11]([C:12](=[O:26])N[C@]2(C(OC(C)(C)C)=O)C[C@H]2C=C)[CH2:10][CH:9]([O:27]C2C3C(=CC(OC)=CC=3)N=C(C3C=CC=CC=3)C=2)[CH:8]=1)=[O:6].Cl>CO>[O:26]=[C:12]1[CH:11]2[CH2:10][CH:9]([CH2:8][CH:7]2[C:5]([OH:4])=[O:6])[O:27]1
Reactant: C=C[C@@H]1C[C@]1(NC(=O)C1CC(Oc2cc(-c3ccccc3)nc3cc(OC)ccc23)C=C1C(=O)OC)C(=O)OC(C)(C)C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)C1CC2CC1C(=O)O2
Reaction time: 4 h
Yield: 89.3 %

Procedure:
Sodium hydroxide (1M, 74 mL, 0.074 mol) was added to a stirred solution of 30 (3.73 g, 0.018 mol) in methanol (105 mL) at room temperature. After 4 h, the reaction mixture was neutralized with 3M HCl, evaporated and co-evaporated with toluene several times. Pyridine (75 mL) and Ac2O (53 mL) were added and the reaction mixture was allowed to shake overnight at room temperature. The mixture was then co-evaporated with toluene and purified by flash column chromatography (ethyl acetate+1% acetic acid) to give the title compound (2.51 g, 88%) as a yellow oil.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]3([CH3:33])[O:26][C:25]4=[N:27][C:28]([N+:30]([O-:32])=[O:31])=[CH:29][N:24]4[CH2:23]3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>>[CH3:33][C:22]1([CH2:21][O:20][C:17]2[CH:16]=[CH:15][C:14]([N:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)=[CH:19][CH:18]=2)[O:26][C:25]2=[N:27][C:28]([N+:30]([O-:32])=[O:31])=[CH:29][N:24]2[CH2:23]1
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(OCC3(C)Cn4cc([N+](=O)[O-])nc4O3)cc2)CC1
Solvent: O=C(O)C(F)(F)F
Product: CC1(COc2ccc(N3CCNCC3)cc2)Cn2cc([N+](=O)[O-])nc2O1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
4-[4-(2-Methyl-6-nitro-2,3-dihydro-imidazo[2,1-b]oxazol-2-ylmethoxy)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester is treated with trifluoroacetic acid (5 ml) and stirred at room temperature for 1 hr. The mixture is concentrated and 2-methyl-6-nitro-2-(4-piperazin-1-yl-phenoxymethyl)-2,3-dihydro-imidazo[2,1-b]oxazole is isolated as a dark oil and used for subsequent step without further purification.
Reaction SMILES: [CH3:1][C:2]([CH3:31])=[CH:3][CH2:4][C:5]1[C:10]([OH:11])=[C:9]2[C:12]([C:14]3[C:19]([CH2:20][CH:21]=[C:22]([CH3:24])[CH3:23])=[C:18]([O:25]C)[C:17]([OH:27])=[CH:16][C:15]=3[O:28][C:8]2=[CH:7][C:6]=1[O:29]C)=[O:13].CC(C)=CCC1C(O)=C2C(C3C(OC2=CC=1O)=CC(O)=C(OC)C=3CC=C(C)C)=O.[C-]#N.[Na+]>CS(C)=O>[CH3:1][C:2]([CH3:31])=[CH:3][CH2:4][C:5]1[C:6]([OH:29])=[CH:7][C:8]2[O:28][C:15]3[CH:16]=[C:17]([OH:27])[C:18]([OH:25])=[C:19]([CH2:20][CH:21]=[C:22]([CH3:23])[CH3:24])[C:14]=3[C:12](=[O:13])[C:9]=2[C:10]=1[OH:11]
Reactant: COc1cc2oc3cc(O)c(OC)c(CC=C(C)C)c3c(=O)c2c(O)c1CC=C(C)C
Agent: COc1c(O)cc2oc3cc(O)c(CC=C(C)C)c(O)c3c(=O)c2c1CC=C(C)C
Agent: [C-]#N
Agent: [Na+]
Solvent: CS(C)=O
Product: CC(C)=CCc1c(O)cc2oc3cc(O)c(O)c(CC=C(C)C)c3c(=O)c2c1O

Procedure:
O-Methyl γ-mangostins such as β-mangostin, 3-O-methyl-γ-mangostin, 6,7-dimethyl-γ-mangostin and 3,6,7-trimethyl-γ-mangostin are conveniently converted to α-mangostin first by demethylation using sodium cyanide (NaCN) in dimethyl sulfoxide (DMSO) and then subjected to inventive O-demethylation process to obtain γ-mangostin in good yield and high purity.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[N:3]=1.[Cl:10][CH2:11][C:12](=O)[CH2:13]Cl>COCCOC>[Cl:10][CH2:11][C:12]1[N:1]=[C:2]2[N:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[N:3]2[CH:13]=1
Reactant: O=C(CCl)CCl
Reactant: Cc1cc(C)nc(N)n1
Solvent: COCCOC
Product: Cc1cc(C)n2cc(CCl)nc2n1
Temperature: 25 °C

Procedure:
A solution of 2-amino-4,6-dimethylpyrimidine (2.46 g, 20.0 mmol) and 1,3-dichloro-2-propanone (2.67 g, 21.0 mmol) in 1,2-dimethoxyethane (20 mL) was stirred at 45° C. overnight. A precipitate formed, and this was collected by filtration, and was then refluxed with ethanol (15 mL) for 2 hours. After cooling to room temperature, the product precipitated as white needles which were collected by filtration and vacuum dried to yield the title compound pure as its hydrochloride salt (883 mg, 19%). 1H NMR (500 MHz, DMSO-d6): δ7.84 (s, 1H), 6.88 (s, 1H), 4.84 (s, 2H), 2.60 (s, 3H), 2.49 (s, 3H).
Reaction SMILES: [BH4-].[Na+].C([O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C@@H:13]1[O:27][C@:17]2([CH2:28][O:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C@@:18]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)([OH:19])[C@H:14]1[O:15][CH2:16]2)C=C.Cl>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCCC1>[CH2:20]([C@@:18]1([OH:19])[C@@:17]2([CH2:16][O:15][C@H:14]1[C@H:13]([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[OH:6])[O:27]2)[CH2:28][O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: C=CCOc1ccccc1[C@@H]1O[C@@]2(COCc3ccccc3)CO[C@@H]1[C@@]2(O)Cc1ccccc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Cl
Agent: [BH4-]
Solvent: C1CCOC1
Product: Oc1ccccc1[C@@H]1O[C@@]2(COCc3ccccc3)CO[C@@H]1[C@@]2(O)Cc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 78.4 %

Procedure:
Tetrakis(triphenylphosphine)palladium(0) (173 mg, 0.15 mmol) and sodium tetrahydroborate (260 mg, 6.9 mmols) were added to an anhydrous tetrahydrofuran (20 ml) solution of the compound (23) (1.05 g, 2.3 mmols), and the mixture was stirred for 8 hours at room temperature. After 1N hydrochloric acid was added, the system was extracted with ethyl acetate 3 times. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting crude product was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1) to obtain colorless crystals (24) (755 mg, 79%).