Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[C@H:3]2[CH2:4][C@H:5]3[C@:18]([CH3:20])([CH2:19][C@@H:2]12)[C@@H:17]1[C@H:8]([C@H:9]2[C@@:13]([CH2:15][CH2:16]1)([CH3:14])[C:12](=[O:21])[C@@H:11]([N:22]1[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]1)[CH2:10]2)[CH2:7][CH2:6]3.[BH4-].[Na+]>C(Cl)Cl.CO>[O:1]1[C@H:3]2[CH2:4][C@H:5]3[C@:18]([CH3:20])([CH2:19][C@@H:2]12)[C@@H:17]1[C@H:8]([C@H:9]2[C@@:13]([CH2:15][CH2:16]1)([CH3:14])[C@@H:12]([OH:21])[C@@H:11]([N:22]1[CH2:23][CH2:24][N:25]([CH3:28])[CH2:26][CH2:27]1)[CH2:10]2)[CH2:7][CH2:6]3
Reactant: CN1CCN([C@H]2C[C@H]3[C@@H]4CC[C@H]5C[C@@H]6O[C@@H]6C[C@]5(C)[C@H]4CC[C@]3(C)C2=O)CC1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Product: CN1CCN([C@H]2C[C@H]3[C@@H]4CC[C@H]5C[C@@H]6O[C@@H]6C[C@]5(C)[C@H]4CC[C@]3(C)[C@H]2O)CC1
Reaction time: 12 h

Procedure:
15 g (0.038 mole) of 2α,3α-epoxy-17-oxo-16β-N-Methyl-piperazino-5α-androstane (Example 9) are dissolved in the mixture of 45 ml of methylene chloride and 120 ml of methanol, whereafter 12 g (0.31 mole) of sodium borohydride are added at a temperature of below 30° C. When the addition is complete, the product of the reduction is crystallized. The crystalline solution is stirred vigorously for 12 hours, whereafter the solvent is distilled at reduced pressure at a temperature of below 40° C. The residue is triturated with water, the crystallized product is filtered, dissolved in chloroform and washed with 5% aqueous sodium hydroxide solution and with water until pH = 7. The layers are separated. The chloroform layer is dried on sodium sulfate, filtered and the filtrate is evaporated to dryness. The residue is recrystallized from acetonitrile. Yield: 11.7 g (77.2%) of 2α,3α-epoxy-17β-N-methyl-piperazino-5α-androstane; m.p. 149°-153° C; [α]D25 = +27.1° (c = 1 in chloroform).
Reaction SMILES: Cl[C:2]1[N:6]([CH3:7])[C:5]2[CH:8]=[CH:9][CH:10]=[CH:11][C:4]=2[N:3]=1.[CH2:12]([N:14]1[C:22]2[C:17](=[N:18][CH:19]=[CH:20][CH:21]=2)[N:16]([C:23]2[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=2)[C:15]1=[O:30])[CH3:13].[H-].[Na+]>CN(C=O)C.CO>[CH2:12]([N:14]1[C:22]2[C:17](=[N:18][CH:19]=[CH:20][CH:21]=2)[N:16]([C:23]2[CH:24]=[CH:25][C:26]([O:29][C:2]3[N:6]([CH3:7])[C:5]4[CH:8]=[CH:9][CH:10]=[CH:11][C:4]=4[N:3]=3)=[CH:27][CH:28]=2)[C:15]1=[O:30])[CH3:13]
Reactant: Cn1c(Cl)nc2ccccc21
Reactant: CCn1c(=O)n(-c2ccc(O)cc2)c2ncccc21
Agent: [H-]
Agent: [Na+]
Solvent: CO
Solvent: CN(C)C=O
Product: CCn1c(=O)n(-c2ccc(Oc3nc4ccccc4n3C)cc2)c2ncccc21
Temperature: 150 °C
Yield: 82.1 %

Procedure:
2-Chloro-1-methyl-1H-benzimidazole (500 mg) was added to a solution of 1-ethyl-3-(4-hydroxyphenyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (789 mg) and NaH (132 mg) in DMF (10 ml) at room temperature. The mixture was heated at 150° C. for 1 h under microwave irradiation. The reaction mixture was diluted with MeOH and concentrated in vacuo. The residue was purified by column chromatography (NH silica gel, eluted with 0%-50% EtOAc in hexane) to give 1-ethyl-3-{4-[(1-methyl-1H-benzimidazol-2-yl)oxy]phenyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (950 mg) as white crystals.
Reaction SMILES: [CH3:1][N:2]([CH3:18])[CH2:3][C@H:4]([CH3:17])[C@:5]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH3:16])[CH:10]=1)(O)[CH2:6][CH3:7].S(=O)(=O)(O)O.CS(O)(=O)=O.C1(C)C=CC(S(O)(=O)=O)=CC=1>O.C1CCCCC1.O1CCCC1>[CH3:16][O:15][C:11]1[CH:10]=[C:9]([C@H:5]([CH2:6][CH3:7])[C@@H:4]([CH3:17])[CH2:3][N:2]([CH3:18])[CH3:1])[CH:14]=[CH:13][CH:12]=1
Reactant: CC[C@](O)(c1cccc(OC)c1)[C@@H](C)CN(C)C
Agent: CS(=O)(=O)O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=S(=O)(O)O
Solvent: O
Solvent: C1CCOC1
Solvent: C1CCCCC1
Product: CC[C@@H](c1cccc(OC)c1)[C@@H](C)CN(C)C
Temperature: 20 °C

Procedure:
Accordingly the compound (2S,3R)-1-(dimethylamino)-3-(3-methoxyphenyl)-2-methyl pentan-3-ol of Formula-V was charged in the solvent tetrahydrofuran and under stirring charged concentrated sulfuric acid at temperature of 20-30° C. The reaction mixture is stirred and charged methanesulfonic acid or para toluenesulfonic acid and solvent cyclohexane. Stirred and raised the temperature to reflux. Maintained the reaction mass at reflux temperature for 3-5 hours with simultaneous removal of water. Cooled the reaction mass to 20° C. and separated the organic layer. Charged the organic layer in an autoclave and diluted the layer with tetrahydrofuran. Charged the catalyst Pd/C. Purged the autoclave with nitrogen gas and followed with hydrogen gas pressure of 5-7 kg. Maintained the reaction mass at 25-30° C. for 2-4 hours. After completion of the reaction the reaction mass was filtered and the filtrate was concentrated under reduced pressure to get the residual mass. Diluted the residual mass with water and extracted with toluene. Separated the aqueous layer and adjusted the pH to 9-10 with aqueous solution of sodium hydroxide. Extracted the aqueous layer with diisopropyl ether, separated the organic layer and concentrated under reduced pressure below 40° C. to get the compound (2R,3R)-3-(3-methoxyphenyl)-N,N,2-trimethylpentan-1-amine of Formula-VII.
Reaction SMILES: [OH-:1].[Na+].C(O[C:6]([C:8]1[CH:12]=[C:11]([C:13]2[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][N:14]=2)[N:10]([C:21]2[N:22]=[N:23][C:24](Cl)=[CH:25][CH:26]=2)[N:9]=1)=[O:7])C.[O:28]1[CH2:32]CCC1>CO>[CH3:32][O:28][C:24]1[N:23]=[N:22][C:21]([N:10]2[C:11]([C:13]3[CH:18]=[C:17]([O:19][CH3:20])[CH:16]=[CH:15][N:14]=3)=[CH:12][C:8]([C:6]([OH:7])=[O:1])=[N:9]2)=[CH:26][CH:25]=1
Reactant: [OH-]
Reactant: C1CCOC1
Reactant: CCOC(=O)c1cc(-c2cc(OC)ccn2)n(-c2ccc(Cl)nn2)n1
Agent: [Na+]
Solvent: CO
Product: COc1ccnc(-c2cc(C(=O)O)nn2-c2ccc(OC)nn2)c1
Reaction time: 1 h
Yield: 34 %

Procedure:
Aqueous 1N sodium hydroxide (14 mL) was added to the above-obtained 1-(6-chloro-3-pyridazinyl)-5-(4-methoxy-2-pyridyl)pyrazole-3-carboxylic acid ethyl ester (2.01 g) in a mixture of methanol (40 mL) and tetrahydrofuran (40 mL) at room temperature, followed by stirring for 1 hour. The reaction solvent was removed under reduced pressure, and water was added to the residue, and the mixture was washed with chloroform. The aqueous layer was partitioned between acetic acid (20 mL) and a methanol-chloroform (1:5) solvent mixture. The organic layer was dried over sodium sulfate anhydrate, followed by filtration. The solvent was removed under reduced pressure, and the residue was dissolved in methanol (14 mL). In an argon atmosphere, sodium methoxide (0.332 g) was added to the resultant solution at room temperature, followed by stirring for 3 hours. The mixture was refluxed under heat for 2 hours, and then cooled in air. The reaction mixture was partitioned by use of acetic acid (10 mL), water, and methanol-chloroform (1:10) solvent mixture. The organic layer was dried over sodium sulfate anhydrate, followed by filtration. The solvent was removed under reduced pressure, to thereby give the title compound as a solid (0.626 g, 34%).
Reaction SMILES: ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[F:13][C:14]([F:32])([F:31])[C:15]1[CH:20]=[CH:19][C:18]([C@@H:21]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:24][CH2:23][NH:22]2)=[CH:17][CH:16]=1.C([N:36]([CH:39]([CH3:41])[CH3:40])CC)(C)C.C1(N)CC1>C(Cl)Cl.O>[CH:39]1([NH:36][C:5]([N:22]2[CH2:23][CH2:24][C:25]3[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=3)[C@H:21]2[C:18]2[CH:17]=[CH:16][C:15]([C:14]([F:13])([F:31])[F:32])=[CH:20][CH:19]=2)=[O:11])[CH2:41][CH2:40]1
Reactant: FC(F)(F)c1ccc([C@H]2NCCc3ccccc32)cc1
Reactant: CCN(C(C)C)C(C)C
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Agent: NC1CC1
Solvent: ClCCl
Solvent: O
Product: O=C(NC1CC1)N1CCc2ccccc2[C@H]1c1ccc(C(F)(F)F)cc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a stirred solution of triphosgene (0.05 mL, 0.4 mmol) in DCM (1 mL) at 0° C. was added a mixture of (R)-1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (0.200 g, 0.7 mmol) and diisopropylethylamine (0.1 mL, 0.8 mmol) in DCM (1 mL). After stirring at 0° C. in 30 min, cyclopropylamine (0.04 mL, 0.7 mmol) was added and the mixture was continued to stir at RT for 24 h. H2O was added and layers were separated. The organic extracts were dried over MgSO4, concentrated and purified by ISCO (20% EtOAc/hexanes) to give the white solid title compound. MS (ESI, positive ion) m/z: 361 (M+1).
Reaction SMILES: ClC1C=CC=C([N+]([O-])=[O:9])C=1C.Cl[C:13]1[C:18]2[C:19](=[O:24])[NH:20][S:21](=[O:23])(=[O:22])[C:17]=2[CH:16]=[CH:15][CH:14]=1>>[OH:9][C:13]1[C:18]2[C:19](=[O:24])[NH:20][S:21](=[O:23])(=[O:22])[C:17]=2[CH:16]=[CH:15][CH:14]=1
Reactant: Cc1c(Cl)cccc1[N+](=O)[O-]
Reactant: O=C1NS(=O)(=O)c2cccc(Cl)c21
Product: O=C1NS(=O)(=O)c2cccc(O)c21

Procedure:
Starting from the 2-chloro-6-nitro toluene, the preparation of the starting compound, 4-chloro-1,2-benzoisothiazol-3(2H)-one-1,1-dioxide, was carried out by one of the following processes:
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:11]=[C:10]([C:12]2[CH:17]=[C:16](Br)[CH:15]=[CH:14][C:13]=2[F:19])[O:9][N:8]=1.[N:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+]>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.COCCOC>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:11]=[C:10]([C:12]2[CH:17]=[C:16]([C:23]3[CH:24]=[CH:25][N:20]=[CH:21][CH:22]=3)[CH:15]=[CH:14][C:13]=2[F:19])[O:9][N:8]=1
Reactant: OB(O)c1ccncc1
Reactant: Fc1ccc(Br)cc1-c1nc(-c2ccccn2)no1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: Fc1ccc(-c2ccncc2)cc1-c1nc(-c2ccccn2)no1
Yield: 4.1 %

Procedure:
In a similar fashion, 3-(2-pyridyl)-5-(5-bromo-2-fluorophenyl)-1,2,4-oxadiazole (100 mg, 0.312 mmole), 4-pyridylboronic acid (76.7 mg, 0.6265 mmol) and Pd(PPh3)4 (36.1 mg, 0.03123 mmol) in a solution of 2M sodium carbonate (4 mL) and ethylene glycol dimethyl ether (4 mL) was heated overnight at 105° C. Standard work up, afforded 4.1 mg (4%) of 3-(2-pyridyl)-5-[2-fluoro-5-(4-pyridyl)phenyl]-1,2,4-oxadiazole.
Reaction SMILES: [Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[N:10]=2)[N:5]=[CH:4][C:3]=1[NH2:14].[F:15][B-:16]([F:19])([F:18])[F:17].[N:20]#[O+]>C1COCC1>[F:15][B-:16]([F:19])([F:18])[F:17].[Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[N:10]=2)[N:5]=[CH:4][C:3]=1[N+:14]#[N:20]
Reactant: N#[O+]
Reactant: COc1ccc2ncc(N)c(Br)c2n1
Agent: F[B-](F)(F)F
Solvent: C1CCOC1
Product: COc1ccc2ncc([N+]#N)c(Br)c2n1
Reaction time: 1 h
Yield: 89.8 %

Procedure:
A solution of 4-bromo-6-methoxy-[1,5]naphthyridin-3-ylamine (25.2 g, 99.2 mmole) in dry THF (400 mL) was maintained at −5° C. while nitrosonium tetrafluoroborate (12.9 g, 110 mmole) was added portionwise over 30 min (approximately 2 g portions). The reaction was continued for an additional 1 hr at −5° C., at which time TLC* and LC/MS indicated that the reaction was complete. The orange solid was collected by suction filtration, washed with ice-cold THF and dried under vacuum to provide the title compound (31.42 g, 90%).
Reaction SMILES: Cl.[NH2:2][CH:3]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:4]([O:6][CH3:7])=[O:5].F[C:15]1[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][C:16]=1[N+:25]([O-:27])=[O:26].CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:7][O:6][C:4](=[O:5])[CH:3]([NH:2][C:15]1[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][C:16]=1[N+:25]([O-:27])=[O:26])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: COC(=O)c1ccc(F)c([N+](=O)[O-])c1
Reactant: COC(=O)C(N)c1ccccc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1ccc(NC(C(=O)OC)c2ccccc2)c([N+](=O)[O-])c1

Procedure:
Methyl 2-amino-2-phenylacetate hydrochloride (500 mg, 2.48 mmol, 1.00 equiv) in DMF (5 mL), methyl 4-fluoro-3-nitrobenzoate (1.0 g, 5.03 mmol, 2.00 equiv), and DIEA (1 g, 7.75 mmol, 3.13 equiv) were combined in a 50-mL round-bottom flask and allowed to react, with stifling, overnight at room temperature. The reaction was then quenched by the addition of 100 mL of water. The solids were collected by filtration, resulting in 0.9 g (crude) of methyl 4-(2-methoxy-2-oxo-1-phenylethylamino)-3-nitrobenzoate as a yellow solid.
Reaction SMILES: [CH2:1]([O:8][C:9]([C@@H:11]([NH:13][C:14]([C@@H:16]1[CH2:21][CH2:20][CH2:19][CH2:18][N:17]1C(OC(C)(C)C)=O)=[O:15])[CH3:12])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:29]>O1CCOCC1>[Cl-:29].[CH2:1]([O:8][C:9]([C@@H:11]([NH:13][C:14]([C@@H:16]1[CH2:21][CH2:20][CH2:19][CH2:18][NH2+:17]1)=[O:15])[CH3:12])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C[C@H](NC(=O)[C@@H]1CCCCN1C(=O)OC(C)(C)C)C(=O)OCc1ccccc1
Reactant: Cl
Solvent: C1COCCO1
Product: C[C@H](NC(=O)[C@@H]1CCCC[NH2+]1)C(=O)OCc1ccccc1
Product: [Cl-]
Temperature: 25 °C
Reaction time: 1 h

Procedure:
2.30 g (5.89 mmol) of the carbamate from example 20A are dissolved in 4N hydrochloric acid in dioxane (23 ml) and stirred at room temperature for 1 h. The solution is subsequently evaporated, taken up again in toluene and concentrated again. The residue is washed with diethyl ether with stirring and filtered off with suction. 1.70 g (88% of th.) of product are obtained, which is employed in the following reaction without further purification.
Reaction SMILES: [O:1]=[C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=[CH:4][NH:3]1.CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>O1CCCC1>[O:1]=[C:2]1[C:7]([C:8]([NH:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:10])=[CH:6][CH:5]=[CH:4][NH:3]1
Reactant: Nc1ccccc1
Reactant: O=C(O)c1ccc[nH]c1=O
Agent: CC(C)COC(=O)Cl
Solvent: CN1CCOCC1
Solvent: C1CCOC1
Product: O=C(Nc1ccccc1)c1ccc[nH]c1=O
Temperature: 0 °C
Reaction time: 6 h
Yield: 97.5 %

Procedure:
To a solution of 2-oxo-1,2-dihydropyridine-3-carboxylic acid (1.00 g, 7.18 mmol) in anhydrous tetrahydrofuran (40 mL) was added 4-methyl morpholine (1.01 g, 10.06 mmol). After cooling to 0° C., isobutyl chloroformate (1.27 g, 9.34 mmol) was added to the reaction mixture. The mixture was stirred at ambient temperature for 6 hours followed by the addition of aniline (0.87 g, 9.34 mmol). The resulting mixture was stirred at ambient temperature for 16 hours. The solvent was removed in vacuo. The residue was dissolved in ethyl acetate (100 mL), and washed with saturated aqueous sodium bicarbonate (2×50 mL) and brine (50 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford the title compound as a colorless solid (1.50 g, 97%): 1H NMR (300 MHz, DMSO-d6) δ 12.71 (br s, 1H), 12.14 (s, 1H), 8.46-8.38 (m, 1H), 7.80-7.52 (m, 1H), 7.65-7.62 (m, 2H), 7.35-7.29 (m, 2H), 7.10-6.95 (m, 1H), 6.58-6.45 (m, 1H); MS (ES+) m/z 215.2 (M+1).
Reaction SMILES: [C:1]([CH2:9][C:10]#[N:11])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:12]1(=O)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.C([O:21]CC)C>>[C:2]1([C:1]2[C:13]3[CH2:14][CH2:15][CH2:16][CH2:17][C:12]=3[NH:11][C:10](=[O:21])[CH:9]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1CCCCC1
Reactant: N#CCC(=O)c1ccccc1
Reactant: CCOCC
Product: O=c1cc(-c2ccccc2)c2c([nH]1)CCCC2
Temperature: 110 °C
Reaction time: 1.5 h

Procedure:
A mixture of benzoylacetonitrile (25 g), cyclohexanone (25 g) and 75% polyphosphoric acid (250 g) is stirred at 50° C. for 30 minutes and further at 110° C. for 1.5 hour. After cooling, the reaction mixture is poured into ice-water and thereto is added diethyl ether (300 ml). The mixture is stirred and the precipitated crystals are collected by filtration. The crystals are recrystallized from N,N-dimethylformamide-ethanol to give the desired compound (27 g), m.p. 285°-288° C.
Reaction SMILES: [CH3:1][C:2]([C@@H:18]1[C:24](=[O:25])[N:23]2[C@@H:19]1[CH2:20][C:21]([S:39][C:40]1[O:41][C:42]([CH3:45])=[N:43][N:44]=1)=[C:22]2[C:26]([O:28]CC1C=CC([N+]([O-])=O)=CC=1)=[O:27])([O:4]C(OCC1C=CC([N+]([O-])=O)=CC=1)=O)[CH3:3].C(O)C.P([O-])([O-])(O)=O.[K+:54].[K+]>O.O1CCOCC1.O.[Pt](=O)=O>[OH:4][C:2]([C@@H:18]1[C:24](=[O:25])[N:23]2[C@@H:19]1[CH2:20][C:21]([S:39][C:40]1[O:41][C:42]([CH3:45])=[N:43][N:44]=1)=[C:22]2[C:26]([O-:28])=[O:27])([CH3:3])[CH3:1].[K+:54]
Reactant: Cc1nnc(SC2=C(C(=O)OCc3ccc([N+](=O)[O-])cc3)N3C(=O)[C@@H](C(C)(C)OC(=O)OCc4ccc([N+](=O)[O-])cc4)[C@H]3C2)o1
Agent: O=[Pt]=O
Agent: O=P([O-])([O-])O
Agent: [K+]
Solvent: CCO
Solvent: O
Solvent: C1COCCO1
Product: Cc1nnc(SC2=C(C(=O)[O-])N3C(=O)[C@@H](C(C)(C)O)[C@H]3C2)o1
Temperature: 25 °C

Procedure:
A mixture of 4-nitrobenzyl (5R, 6R)-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-3-(5-methyl-1,3,4-oxadiazol-2-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (50 mg), platinum (IV) oxide monohydrate (50 mg), ethanol (0.5 ml) and 0.1M aqueous solution of dipotassium hydrogen phosphate (2.35 ml) in a mixture of water (2.5 ml) and dioxane (6 ml) was shaken under a hydrogen atmosphere (40 psi) at ambient temperature for an hour. After the catalyst was filtered off, the filtrate was evaporated to half of the original volume. The resultant aqueous solution was washed three times with diethyl ether and then evaporated in vacuo. The residue was dissolved in water (25 ml) and the resultant aqueous solution was chromatographed on nonionic adsorption resin "Diaion HP-20AG" eluting with water (100 ml) and 10% aqueous isopropyl alcohol (100 ml). The fractions, whose UV spectra showed λmax 292 nm, were combined and lyophilized to give potassium (5R, 6R)-6-(1-hydroxy-1-methylethyl)-3-(5-methyl-1,3,4-oxadiazol-2-ylthio)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (14.3 mg) as powder.
Reaction SMILES: [C:1]1([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:6]=[CH:5][C:4](CC([O-])=O)=[CH:3][CH:2]=1.[Na+].F[B-](F)(F)F.[C:23]1([C:29]2[CH:34]=[C:33]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH:32]=[C:31]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[O+]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[C:47](OC(=O)C)(=O)C>>[C:23]1([C:29]2[CH:47]=[C:31]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[CH:32]=[C:33]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:34]=2[C:14]2[CH:15]=[CH:16][C:11]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[CH:12][CH:13]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: O=C([O-])Cc1ccc(-c2ccccc2)cc1
Reactant: CC(=O)OC(C)=O
Reactant: c1ccc(-c2cc(-c3ccccc3)[o+]c(-c3ccccc3)c2)cc1
Agent: F[B-](F)(F)F
Agent: [Na+]
Product: c1ccc(-c2ccc(-c3c(-c4ccccc4)cc(-c4ccccc4)cc3-c3ccccc3)cc2)cc1

Procedure:
Sodium 4-biphenylacetate (25.0 g, 0.106 mmol.) was placed in a suspension of 2,4,6-triphenylpyrylium tetrafluoroborate (41.0 g, 0.106 mol.) in 80 mL of acetic anhydride under nitrogen atmosphere and refluxed for 24 hours. The crude product was extracted with a 7:3 ratio mixture of hexane/dichloromethane. The solvent was stripped, and the crude product sublimed 4 times to achieve 99% purity. The practical yield following sublimations was 20%.
Reaction SMILES: CS(O[CH2:6][C:7]1([CH2:11][N:12]2[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[N:13]2)[CH2:10][O:9][CH2:8]1)(=O)=O.C([O-])([O-])=O.[K+].[K+].[CH3:26][NH:27][CH3:28]>C(#N)C.C(Cl)Cl>[CH3:26][N:27]([CH3:28])[CH2:6][C:7]1([CH2:11][N:12]2[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[CH:14]=[N:13]2)[CH2:10][O:9][CH2:8]1
Reactant: CNC
Reactant: CS(=O)(=O)OCC1(Cn2cc([N+](=O)[O-])cn2)COC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: ClCCl
Product: CN(C)CC1(Cn2cc([N+](=O)[O-])cn2)COC1
Temperature: 70 °C
Yield: 15 %

Procedure:
(3-((4-nitro-1H-pyrazol-1-yl)methyl)oxetan-3-yl)methyl methanesulfonate (0.225 g, 0.935 mmol) was suspended in acetonitrile (6 mL) with K2CO3 (0.297 g, 2.15 mmol) and dimethylamine (2M in MeOH, 1.87 mL, 3.75 mmol) in a microwave vial and sealed under Nitrogen. This was heated at 70° C. for 36 h then diluted with DCM (20 mL), washed with water (20 mL) and brine (20 mL). The organics were dried over Na2SO4, filtered and the solvent removed under vacuum. The crude product was purified by prep HPLC to give N,N-dimethyl-1-(3-((4-nitro-1H-pyrazol-1-yl)methyl)oxetan-3-yl)methanamine as a white so lid (33 mg, 15% yield).
Reaction SMILES: [N+:1]([CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])#[C-:2].CC(C)([O-:12])C.[K+].C[O:16][C:17]1[CH2:34][CH2:33][C@@:32]2([CH3:35])[C:19](=[CH:20][CH2:21][C@@H:22]3[C@:31]2([OH:36])[CH2:30][CH2:29][C@@:27]2([CH3:28])[C@H:23]3[CH2:24][CH2:25][C:26]2=O)[CH:18]=1>O1CCCC1>[CH:2]([NH:1]/[C:3](=[C:26]1/[CH2:25][CH2:24][C@@H:23]2[C@:27]/1([CH3:28])[CH2:29][CH2:30][C@@:31]1([OH:36])[C@H:22]2[CH2:21][CH2:20][C:19]2[C@:32]1([CH3:35])[CH2:33][CH2:34][C:17](=[O:16])[CH:18]=2)/[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[O:12]
Reactant: COC1=CC2=CC[C@H]3[C@@H]4CCC(=O)[C@@]4(C)CC[C@]3(O)[C@@]2(C)CC1
Reactant: [C-]#[N+]CC(=O)OCC
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CCOC(=O)/C(NC=O)=C1\CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@@]3(O)CC[C@]12C
Temperature: 25 °C
Reaction time: 4 h

Procedure:
Ethyl isocyanoacetate (1.64 g) in dry tetrahydrofuran (8 ml) was added slowly to a stirred suspension of potassium tert. butoxide (1.71 g) in dry tetrahydrofuran (60 ml) so that the temperature did not rise above 5° C. A solution of 3-methoxy-9α-hydroxyandrosta-3,5-dien-17-one (3.22 g) in dry tetrahydrofuran (15 ml) was added dropwise at 0° C. and the mixture was stirred at room temperature for 4 hours. Most of tetrahydrofuran was removed under reduced pressure and the product was taken up in cold water, adjusted to pH 0.8 with 4N aqueous hydrochloric acid and extracted with chloroform. The combined chloroform extracts were dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the product dried under vacuum. Yield 3.55 g. NMR spectra showed predominantly the formation of the title compound together with small amounts of ethyl (20E)-20-formamido-9α-hydroxy-3-oxopregna-4,17(20)-dien-21-oate and tert. butyl (20Z)-20-formamide-9α-hydroxy- 3-oxopregna-4,17(20)-dien-21-oate. The compounds were isolated through chromatography and separately identified through spectral data.
Reaction SMILES: C([O-])(C)(C)C.[K+].Cl[CH2:8][C:9]([C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[CH2:16][CH:15]([NH:20][S:21]([C:24]1[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=1)(=[O:23])=[O:22])[CH2:14]2)=[O:10].[C:31]([O:39][CH2:40][CH3:41])(=[O:38])[CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34].C(O)(=O)C>CS(C)=O.O>[C:31]([CH:32]([CH2:8][C:9]([C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[CH2:16][CH:15]([NH:20][S:21]([C:24]1[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=1)(=[O:23])=[O:22])[CH2:14]2)=[O:10])[C:33]([O:35][CH2:36][CH3:37])=[O:34])([O:39][CH2:40][CH3:41])=[O:38]
Reactant: CCOC(=O)CC(=O)OCC
Reactant: Cc1ccc(S(=O)(=O)NC2Cc3ccc(C(=O)CCl)cc3C2)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: CC(=O)O
Solvent: O
Product: CCOC(=O)C(CC(=O)c1ccc2c(c1)CC(NS(=O)(=O)c1ccc(C)cc1)C2)C(=O)OCC
Reaction time: 8 h

Procedure:
10.6 g (0.095 mol) of potassium tert.-butanolate, followed by 23.0 g (0.063 mol) of (2-p-toluenesulphonamido-indan-5-yl) chloromethyl ketone, are added to 15.2 g (0.095 mol) of diethyl malonate in 25 ml of dimethyl sulphoxide. The mixture is allowed to stand overnight and is neutralised with glacial acetic acid, and water and petroleum ether are added. The reaction product which is precipitated is separated off and dissolved in ethyl acetate. The organic phase is washed with water, dried and evaporated, and the residue obtained is purified by chromatography over 600 g of silica gel using 98:2 ethylene chloride/ethanol.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(=O)(=O)(O)O.[CH3:19]O>>[CH3:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:3]=1[C:4]([O:6][CH3:19])=[O:5]
Reactant: Cc1ccc([N+](=O)[O-])cc1C(=O)O
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)c1cc([N+](=O)[O-])ccc1C
Yield: 74 %

Procedure:
2-methyl-5-nitrobenzoic acid (24 g) was dissolved in methanol (240 ml) and concentrated sulfuric acid (8 ml). The mixture was stirred at reflux overnight. Upon cooling the ester crystallized out. The material was isolated by filtration to afford methyl 2-methyl-5-nitrobenzoate as a white solid (19.0 g, 74% yield). A second crop of material (4.92 g, 19% yield) was isolated upon concentration and addition of water to the mother liquor.