Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[CH:11][N+:10]([O-])=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[Si]([C:18]#[N:19])(C)C.C(Cl)(=O)C.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[C:1]1([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([C:18]#[N:19])[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C[Si](C)(C)C#N
Reactant: [O-][n+]1ccc(-c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)Cl
Product: N#Cc1cc(-c2ccccc2)ccn1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 4-phenylpyridine N-oxide (5 g) in DCM (50 mL) was added at RT trimethylsilylcyanide (11 mL), followed by acetyl chloride (3.1 mL) over 10 min. The reaction mixture was stirred overnight at RT. A solution of aq. 10% Na2CO3 was added and the mixture was extracted with EA. The combined org. phases were washed with brine, dried (Na2SO4) and evaporated off. Filtration over a plug of silica gel (Hept/EA 1/1) gave the desired compound (450 mg).
Reaction SMILES: [CH2:1]([C:3]1[N:4]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:5]2[CH2:6][CH2:7][CH2:8][C:9](=[O:12])[C:10]=2[CH:11]=1)[CH3:2].[H-].[Na+].C1(S(OC)=O)C=CC=CC=1.O>O1CCCC1.C(O)(=O)C>[CH2:1]([C:3]1[N:4]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:5]2[C:10]([CH:11]=1)=[C:9]([OH:12])[CH:8]=[CH:7][CH:6]=2)[CH3:2]
Reactant: CCc1cc2c(n1Cc1ccccc1-c1ccccc1)CCCC2=O
Agent: COS(=O)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Solvent: C1CCOC1
Product: CCc1cc2c(O)cccc2n1Cc1ccccc1-c1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 39.3 %

Procedure:
2-Ethyl-1,5,6,7-tetrahydro-1-(2-phenyl-phenylmethyl)-4H-indol-4-one (2.17 g, 0.0066 mol) dissolved in 10 mL of tetrahydrofuran was added to a slurry of sodium hydride (0.58 g) in 3 mL of tetrahydrofuran and the mixture was stirred for 15 min at room temperature. Methyl benzene sulfinate (1.13 g) was added and the solution stirred overnight. The reaction mixture was poured into water, the pH adjusted to 6 with acetic acid and extracted with toluene. The organic layer was separated, washed with water and brine, dried with sodium sulfate, concentrated, taken up in toluene (80 mL) and heated at reflux for 1.5 h. After cooling, the mixture was concentrated, dissolved in ether (100 mL), washed with saturated sodium bicarbonate solution, dried over sodium sulfate, concentrated and purified by flash chromatography on silica eluting with 10:1 hexane/ethyl acetate to afford 0.85 g of subtitled material.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([O:22][CH2:23][CH2:24][CH3:25])=[C:8]([C:10]2[NH:15][C:14](=[O:16])[C:13]([C:17]3[NH:21][N:20]=[N:19][N:18]=3)=[CH:12][N:11]=2)[CH:9]=1)([O-])=O.[H][H]>COCCO>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([O:22][CH2:23][CH2:24][CH3:25])=[C:8]([C:10]2[NH:15][C:14](=[O:16])[C:13]([C:17]3[NH:21][N:20]=[N:19][N:18]=3)=[CH:12][N:11]=2)[CH:9]=1
Reactant: [H][H]
Reactant: CCCOc1ccc([N+](=O)[O-])cc1-c1ncc(-c2nnn[nH]2)c(=O)[nH]1
Solvent: COCCO
Product: CCCOc1ccc(N)cc1-c1ncc(-c2nnn[nH]2)c(=O)[nH]1
Reaction time: 19 h
Yield: 78.9 %

Procedure:
A mixture of 2-(5-nitro-2-n-propoxyphenyl)-5-(5-1H-tetrazolyl)pyrimidine-4(3H)-one (5.0 g.) and 10% paladium-on-carbon (4.0 g.) in 2-methoxyethanol (900 ml.) was shaken in an atmosphere of hydrogen at an initial pressure of 3.5 kg./cm2 for 19 hours. The mixture was filtered and the filtrate evaporated to dryness to give the title compound (3.6 g., 79%), m.p. 250°-253° (decomp). Recrystallization from 2-methoxyethanol gave analytical material, m.p. 261°-262°.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:21]([NH:22][C:23]2[CH:28]=[CH:27][C:26](I)=[CH:25][C:24]=2[CH3:30])=[C:20]([F:31])[C:8]2[N:9]=[C:10]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[NH:11][C:7]=2[CH:6]=1)=[O:4].[CH3:32][N:33](C=O)C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[C-]#N.[C-]#N.[Zn+2]>[CH3:1][O:2][C:3]([C:5]1[C:21]([NH:22][C:23]2[CH:28]=[CH:27][C:26]([C:32]#[N:33])=[CH:25][C:24]=2[CH3:30])=[C:20]([F:31])[C:8]2[N:9]=[C:10]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[NH:11][C:7]=2[CH:6]=1)=[O:4]
Reactant: CN(C)C=O
Reactant: COC(=O)c1cc2[nH]c(COCC[Si](C)(C)C)nc2c(F)c1Nc1ccc(I)cc1C
Agent: [Fe+2]
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Product: COC(=O)c1cc2[nH]c(COCC[Si](C)(C)C)nc2c(F)c1Nc1ccc(C#N)cc1C
Temperature: 120 °C
Yield: 77 %

Procedure:
To a stirred solution of a 1:1 mixture of N1:N3 isomers of 7-fluoro-6-(4-iodo-2-methyl-phenylamino)-(2-trimethylsilanyl-ethoxymethyl)-benzoimidazole-5-carboxylic acid methyl ester 10jj (0.060 g, 0.108 mmol) in 1 mL DMF at room temperature under N2 is added dppf (2 mg, 0.004 mmol) followed by Pd2 dba3 (2 mg, 0.002 mmol) and Zn(CN)2 (8 mg, 0.065 mmol) (Tetrahedron Lett. 1999, 40, 8193-8195). The reaction mixture is heated to 120° C. for 45 minutes. The reaction mixture is cooled to room temperature and quenched by the addition of 5 mL of a 4:1:5 mixture of sat NH4Cl:conc NH4OH:water. The aqueous layer is extracted with ethyl acetate. The combined organic extracts are washed with water (3×), brine, and dried (MgSO4) and concentrated under reduced pressure. Purification by flash column chromatography eluted with 1:1 hexanes:ethyl acetate provides 38 mg (77%) of desired product as a 1:1 mixture of N1 and N3 isomers: APCI MS (+) m/z 455 (M+1) detected.
Reaction SMILES: [CH:1]1[CH:6]=[N:5][CH:4]=[C:3]([C:7]2[CH2:11][CH2:10][CH2:9][N:8]=2)[CH:2]=1>CO.[Pd]>[CH:1]1[CH:6]=[N:5][CH:4]=[C:3]([CH:7]2[NH:8][CH2:9][CH2:10][CH2:11]2)[CH:2]=1
Reactant: c1cncc(C2=NCCC2)c1
Agent: [Pd]
Solvent: CO
Product: c1cncc(C2CCCN2)c1
Yield: 84.6 %

Procedure:
Myosmine (32 g, 0.219 mol) was dissolved in 150 ml of methanol and hydrogenated at atmospheric pressure with 1.3 g of 10% palladium on carbon as catalyst. After 5 hours the mixture was filtered and the filtrate was concentrated to get a brown solid (32 g, 94.9% purity by GC). It was further purified by vacuum distillation at 0.1 mm Hg to get pure nornicotine (27.46 g, 84.7% yield, 97.5% purity by GC). 1H NMR (CDCl3): δ 1.66-2.72 (2H,m), 3.0 (2H,m), 4.13 (1H,t), 7.24 (1H,m), 7.69 (1H, dt), 8.46 (1H,dd), and 8.59 (1H,d). 13C-NMR (CDCl3): δ 148.4, 148.1, 140.16, 134.1, 123.3, 60.0, 46.8, 34.2, and 25.4. IR: 3291, 2960, 1641, 1578 Cm−1.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH:9]([C:11]1[C:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)=[C:19]([C:27](O)=[O:28])[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([F:30])[CH:17]=2)[N:12]=1)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:31]([NH:34][NH2:35])(=[O:33])[CH3:32].Cl.CN(C)CCCN=C=NCC.N1C2C(=NC=CC=2)N(O)N=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CN(C=O)C>[C:31]([NH:34][NH:35][C:27]([C:19]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([F:30])[CH:17]=2)[N:12]=[C:11]([CH:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH3:10])[C:20]=1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1)=[O:28])(=[O:33])[CH3:32]
Reactant: CC(=O)NN
Reactant: CC(NC(=O)OC(C)(C)C)c1nc2ccc(F)cc2c(C(=O)O)c1-c1ccccn1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C([O-])O
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(=O)NNC(=O)c1c(-c2ccccn2)c(C(C)NC(=O)OC(C)(C)C)nc2ccc(F)cc12
Temperature: 25 °C
Reaction time: 15 h

Procedure:
A solution of 2-(1-(tert-butoxycarbonylamino)ethyl)-6-fluoro-3-(pyridin-2-yl)quinoline-4-carboxylic acid (2.011 g, 4.89 mmol) and acetic hydrazide (0.543 g, 7.33 mmol) in DCM (10.99 mL) and DMF (1.222 mL) was treated 0° C. with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC.HCl) (2.81 g, 14.66 mmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (HOAt) (1.995 g, 14.66 mmol), and sodium bicarbonate (1.232 g, 14.66 mmol) successively at 0° C. Then the reaction was stirred at rt. After 15 h, the reaction was partitioned between DCM (100 mL) and 1.0 M aq LiCl (100 mL). The separated aq layer was extracted with DCM (1×100 mL) and the combined organic extracts were washed with 1.0 M aq LiCl (100 mL), dried over MgSO4 and concentrated in vacuo. The crude material was purified by silica gel column chromatography eluting with a gradient of 0% to 50% EtOAc in hexane, to provide tert-butyl 1-(4-(2-acetylhydrazinecarbonyl)-6-fluoro-3-(pyridin-2-yl)quinolin-2-yl)ethylcarbamate as off-white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 10.44 (1H, s), 9.81 (1H, s), 8.69 (1H, d, J=4.7 Hz), 8.37 (1H, dd, J=10.4, 2.7 Hz), 8.16 (1H, dd, J=9.2, 5.5 Hz), 7.93 (1H, td, J=7.7, 1.8 Hz), 7.77 (1H, td, J=8.8, 2.7 Hz), 7.56 (1H, d, J=7.6 Hz), 7.47 (1H, dd, J=7.0, 5.3 Hz), 7.02 (1H, d, J=7.6 Hz), 4.70-4.82 (1H, m), 1.87 (3H, s), 1.31 (9H, s), 1.22 (3H, d, J=6.7 Hz); LC-MS (ESI) m/z 468.1 [M+H]+.
Reaction SMILES: CS(O[CH2:6][CH2:7][NH:8][C:9]1[C:13]([C:14]2[N:18]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=3)[C:17](=[O:29])[O:16][N:15]=2)=[N:12][O:11][N:10]=1)(=O)=O.[N-:30]=[N+:31]=[N-:32].[Na+].O>CN(C)C=O>[N:30]([CH2:6][CH2:7][NH:8][C:9]1[C:13]([C:14]2[N:18]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=3)[C:17](=[O:29])[O:16][N:15]=2)=[N:12][O:11][N:10]=1)=[N+:31]=[N-:32]
Reactant: CS(=O)(=O)OCCNc1nonc1-c1noc(=O)n1-c1cccc(C(F)(F)F)c1
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: [N-]=[N+]=NCCNc1nonc1-c1noc(=O)n1-c1cccc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 6 h
Yield: 94.7 %

Procedure:
2-[(4-{5-Oxo-4-[3-(trifluoromethyl)phenyl]-4,5-dihydro-1,2,4-oxadiazol-3-yl}-1,2,5-oxadiazol-3-yl)amino]ethyl methanesulfonate (1.2 g, 2.9 mmol) was dissolved in N,N-dimethylformamide (2.7 mL). After sodium azide (280 mg, 4.3 mmol) was added in one portion, the temperature was brought to 65° C. and the reaction stirred for 6 hours. After cooling back to room temperature, water (10 mL) was added to quench the reaction. The product was extracted with ethyl acetate (3×10 mL) and the combined organic layers were dried over sodium sulfate. The solvent was removed in vacuo to give the desired product (1.05 g, 96%). LCMS calculated for C13H10F3N6O3 (M-N2+H)+: m/z=355.0. 1H NMR (400 MHz, DMSO-d6): δ 8.09 (s, 1H), 7.93 (m, 2H), 7.79 (t, J=8.2 Hz, 1H), 6.75 (t, J=5.8 Hz, 1H), 3.52 (t, J=5.7 Hz, 2H), 3.44 (q, J=5.5 Hz, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]2[NH:9][C:8](=[O:13])[C:7]3[S:14][CH:15]=[CH:16][C:6]=3[C:5]=2[C:4]=1[C:17]1[CH:22]=[CH:21][C:20]([C@@H:23]([CH3:33])[CH2:24][NH:25]C(=O)OC(C)(C)C)=[CH:19][CH:18]=1>C(O)(C(F)(F)F)=O>[NH2:25][CH2:24][C@@H:23]([C:20]1[CH:19]=[CH:18][C:17]([C:4]2[C:5]3[C:6]4[CH:16]=[CH:15][S:14][C:7]=4[C:8](=[O:13])[NH:9][C:10]=3[CH:11]=[CH:12][C:3]=2[O:2][CH3:1])=[CH:22][CH:21]=1)[CH3:33]
Reactant: COc1ccc2[nH]c(=O)c3sccc3c2c1-c1ccc([C@@H](C)CNC(=O)OC(C)(C)C)cc1
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc2[nH]c(=O)c3sccc3c2c1-c1ccc([C@@H](C)CN)cc1
Yield: 81.3 %

Procedure:
Following General Procedure C (R)-tert-butyl 2-(4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl)propylcarbamate (2.5 g, 5.4 mmol) was reacted with TFA (10 mL) to afford the desired product (1.6 g, 81%) as an off-white solid: ESI MS m/z 365 [C21H20N2O2S+H]+
Reaction SMILES: [H][H].[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[N:13][O:14][C:15]=2[C:16]2[CH:21]=[C:20]([O:22][CH3:23])[C:19]([O:24][CH3:25])=[C:18]([O:26][CH3:27])[CH:17]=2)=[CH:7][C:6]=1[N+:28]([O-])=O.C1COCC1.[ClH:36]>CO.[Pd]>[ClH:36].[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[N:13][O:14][C:15]=2[C:16]2[CH:17]=[C:18]([O:26][CH3:27])[C:19]([O:24][CH3:25])=[C:20]([O:22][CH3:23])[CH:21]=2)=[CH:7][C:6]=1[NH2:28]
Reactant: COc1ccc(-c2cnoc2-c2cc(OC)c(OC)c(OC)c2)cc1[N+](=O)[O-]
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: C1CCOC1
Solvent: CO
Product: COc1ccc(-c2cnoc2-c2cc(OC)c(OC)c(OC)c2)cc1N

Procedure:
A 200-mL round-bottom flask equipped with T-bore stopcock connected to a balloon with hydrogen was charged with 4 (4.44 g, 11.5 mmol) and THF (40 mL), and a mixture was stirred to dissolve a substrate. Methanol (22 mL), solution of HCl in methanol (1M, 22 mL) and palladium, 10 wt % on activated carbon (532 mg, 12 wt %) were added to the flask, the system was evacuated and stirred under atmosphere of hydrogen for 2 hours. TLC indicated completion of reaction (Hexane/EtOAc, 2:1, developed two times). Catalyst was filtered out and washed with methanol (15 mL×3). Filtrate was diluted with 2-propanol (20 mL) and concentrated under reduced pressure to ˜20 mL volume. A resulted suspension was diluted with EtOAc (20 mL), a solid was filtered out, washed with EtOAc (20×2) and dried to give crude amine hydrochloride 5 as a yellow solid, 3.3 g (80%), LC purity 97.1%. The solid was refluxed in ethanol (50 mL) for 15 min to dissolve colored impurities. A cooled suspension was filtered out, washed with EtOAc (20×2) and vacuum-dried to obtain a creamy-colored solid, 2.9 g (70%), LC purity 99.1%.
Reaction SMILES: C1(O)C=CC=CC=1.C=O.C1C=[C:18]2[C:13]([CH:14]=[C:15]([C:20]([O-:22])=O)[CH:16]=[CH:17]2)=CC=1.[CH:23]1[CH:32]=[C:31]2[C:26]([CH:27]=C(C([O-])=O)C=C2)=[CH:25][CH:24]=1.[Pb+2]>>[CH2:27]([O:22][CH2:20][C:15]1[CH:14]=[CH:13][CH:18]=[CH:17][CH:16]=1)[C:26]1[CH:31]=[CH:32][CH:23]=[CH:24][CH:25]=1
Reactant: O=C([O-])c1ccc2ccccc2c1
Agent: C=O
Agent: [Pb+2]
Solvent: Oc1ccccc1
Product: c1ccc(COCc2ccccc2)cc1
Temperature: 130 °C

Procedure:
A benzyl ether-type phenolic resin was prepared in a known method by the condensation reaction of 470 kg of phenol and 479 kg of 47% formalin in the presence of lead naphthenate as the catalyst followed by the removal of the unreacted phenol and formaldehyde as well as water and the like volatile matter under reduced pressure with heating up to a maximum temperature of 130° C. The thus obtained phenolic resin was solid at room temperature and had a softening point of 60° C.
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][OH:14].[N].[C:16](Cl)(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>N1C=CC=CC=1>[C:16]([O:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][Br:1])(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: OCCCCCCCCCCCCBr
Agent: [N]
Solvent: c1ccncc1
Product: O=C(OCCCCCCCCCCCCBr)c1ccccc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 65 %

Procedure:
In a 100 mL two-neck flask under a static head of nitrogen 12-bromo-dodecanol (5.0 g, 18.9 mmol) is weighed, pyridine (25 mL) is added and the whole is brought to 0° C. with an external bath of ice and salt. Benzoyl chloride is dripped slowly and, when adding is finished, the ice bath is removed and the whole is left stirring at room temperature. After 18 hours ethyl acetate (100 mL) and distilled water (100 mL) are added. The organic phase is washed 3 times with distilled water (3×50 mL) and anhydrified on anhydrous sodium sulphate. It is filtered under a vacuum and the solvent is eliminated in the Rotovapor and in the high vacuum pump. The product is purified with column chromatography on silica gel with an eluant mixture of petroleum ether/ethylic ether 5/1. 4.5 g of 12-bromododecyl benzoate are isolated as a colourless oil with a yield of 65%.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([Br:19])[CH:18]=[C:13]3[C:12](I)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Mg]Cl)(C)C.[C:26]([O:30][C:31](=[O:51])[N:32]([C:42]1[CH:47]=[CH:46][C:45]([CH:48]=[O:49])=[C:44]([F:50])[N:43]=1)[CH2:33][C:34]1[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=1)([CH3:29])([CH3:28])[CH3:27].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[C:26]([O:30][C:31](=[O:51])[N:32]([C:42]1[CH:47]=[CH:46][C:45]([CH:48]([C:12]2[C:13]3[C:14](=[N:15][CH:16]=[C:17]([Br:19])[CH:18]=3)[N:10]([S:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)(=[O:9])=[O:8])[CH:11]=2)[OH:49])=[C:44]([F:50])[N:43]=1)[CH2:33][C:34]1[CH:35]=[CH:36][C:37]([O:40][CH3:41])=[CH:38][CH:39]=1)([CH3:29])([CH3:27])[CH3:28]
Reactant: COc1ccc(CN(C(=O)OC(C)(C)C)c2ccc(C=O)c(F)n2)cc1
Reactant: O=S(=O)(c1ccccc1)n1cc(I)c2cc(Br)cnc21
Agent: CC(C)[Mg]Cl
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Solvent: C1CCOC1
Product: COc1ccc(CN(C(=O)OC(C)(C)C)c2ccc(C(O)c3cn(S(=O)(=O)c4ccccc4)c4ncc(Br)cc34)c(F)n2)cc1
Temperature: 5 °C
Yield: 88.1 %

Procedure:
To a solution of 1-benzenesulfonyl-5-bromo-3-iodo-1H-pyrrolo[2,3-b]pyridine (165, 1.00 g, 2.16 mmol) in 7 mL of tetrahydrofuran at −50° C. under nitrogen, isopropylmagnesium chloride (1.18 mL, 2.35 mmol) was added slowly. The reaction was warmed to 5° C. over 70 minutes, then cooled to −45° C. and (6-fluoro-5-formyl-pyridin-2-yl)-(4-methoxy-benzyl)-carbamic acid tert-butyl ester (83, 0.678 g, 1.88 mmol) in 3.0 mL of tetrahydrofuran was added. The reaction was allowed to warm to room temperature over 2-3 hours. The reaction was mixed with aqueous 1 N citric acid and extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography eluting with ethyl acetate and hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound as a white solid (166, 1.155 g). MS (ESI) [M+H]+=696.4 and 698.3.
Reaction SMILES: [CH3:1][C:2]1([CH3:29])[O:6][C:5](=[O:7])/[C:4](=[CH:8]/[C:9]([O:11][Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)=[O:10])/[O:3]1.C(O)(=O)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C>[CH3:1][C:2]1([CH3:29])[O:3][C:4](=[CH:8][C:9]([OH:11])=[O:10])[C:5](=[O:7])[O:6]1
Reactant: CC1(C)OC(=O)/C(=C/C(=O)O[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)O1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CC1(C)OC(=O)C(=CC(=O)O)O1
Reaction time: 0.25 h
Yield: 85.2 %

Procedure:
A solution of pure (Z)-2,2 dimethyl-5-(t-butyldiphenylsilyloxy-carbonylmethylene)-1,3-dioxolan-4-one (2.80 g, 6.82 mmol) in tetrahydrofuran (40 ml) was treated at 22° C. with acetic acid (2 ml) followed by 6.8 ml of a 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran. After 15 minutes at 22° C., the reaction mixture was diluted with ethyl acetate, washed with water, brine and dried (magnesium sulfate). The solvent was concentrated under reduced pressure and the residue was triturated with toluene to give 1.00 g (85% yield) of the title compound as a white crystalline material: mp 203–204° C. (dec.). IR (KBr) ν max (cm−1): 1805, 1707 and 1662. 1H NMR (400 MHz, CDCl3) δ: 1.78 (s, 6), 5.89 (s, 1). Anal. calcd for C7H8O5: C, 48.84; H, 4.68. Found: C, 48.84; H, 4.65.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:14][C:15]2[C:20]([C:21]3[S:22][CH:23]=[CH:24][CH:25]=3)=[C:19]([O:26][CH2:27][CH2:28][OH:29])[N:18]=[C:17]([C:30]3[N:35]=[CH:34][CH:33]=[CH:32][N:31]=3)[N:16]=2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Br:38][C:39]1[CH:40]=[N:41][C:42](Cl)=[N:43][CH:44]=1.Cl>O1CCCC1.CC(N(C)C)=O>[Br:38][C:39]1[CH:40]=[N:41][C:42]([O:29][CH2:28][CH2:27][O:26][C:19]2[N:18]=[C:17]([C:30]3[N:35]=[CH:34][CH:33]=[CH:32][N:31]=3)[N:16]=[C:15]([NH:14][S:11]([C:8]3[CH:7]=[CH:6][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:10][CH:9]=3)(=[O:12])=[O:13])[C:20]=2[C:21]2[S:22][CH:23]=[CH:24][CH:25]=2)=[N:43][CH:44]=1
Reactant: Clc1ncc(Br)cn1
Reactant: CC(C)(C)c1ccc(S(=O)(=O)Nc2nc(-c3ncccn3)nc(OCCO)c2-c2cccs2)cc1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)N(C)C
Product: CC(C)(C)c1ccc(S(=O)(=O)Nc2nc(-c3ncccn3)nc(OCCOc3ncc(Br)cn3)c2-c2cccs2)cc1
Reaction time: 0.33 h
Yield: 26.4 %

Procedure:
To a solution of 4-tert-butyl-N-{6-(2-hydroxyethoxy)-5-(2-thienyl)-2-(2-pyrimidinyl)-pyrimidin-4-yl}benzenesulfonamide (1790 mg) in tetrahydrofuran (20 ml) is added sodium hydride (60% dispersion, 413 mg) at room temperature, and thereto is added dimethylacetamide (4 ml), and the mixture is stirred for 20 minutes. To the reaction mixture is added 5-bromo-2-chloro-pyrimidine (952 mg), and the mixture is stirred at room temperature for 46 hours. The mixture is acidified with 10% hydrochloric acid, and extracted with ethyl acetate. The ethyl acetate layer is washed, dried, and evaporated under reduced pressure to remove the solvent. The residue is purified by silica gel column chromatography (solvent; chloroform:methanol=4:1) to give the title compound (617 mg) as a crystal.
Reaction SMILES: [CH3:1][C:2]1[C:18](=[O:19])[CH2:17][CH2:16][C@@:15]2([CH3:20])[C:3]=1[CH2:4][CH2:5][C@@H:6]1[C@@H:14]2[CH2:13][CH2:12][C@@:11]2([CH3:21])[C@H:7]1[CH2:8][CH2:9][C@@H:10]2[OH:22].OO.[O-:25]S([O-])=O.[Na+].[Na+].[Na+].[Cl-]>CO.[OH-].[Na+].O>[CH3:1][C@:2]12[O:25][C@:3]31[C@:15]([CH3:20])([CH2:16][CH2:17][C:18]2=[O:19])[C@@H:14]1[C@H:6]([C@H:7]2[C@@:11]([CH2:12][CH2:13]1)([CH3:21])[C@@H:10]([OH:22])[CH2:9][CH2:8]2)[CH2:5][CH2:4]3
Reactant: CC1=C2CC[C@H]3[C@@H]4CC[C@H](O)[C@@]4(C)CC[C@@H]3[C@@]2(C)CCC1=O
Reactant: O=S([O-])[O-]
Agent: OO
Agent: [Cl-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: C[C@]12CC[C@H]3[C@@H](CC[C@@]45O[C@]4(C)C(=O)CC[C@]35C)[C@@H]1CC[C@@H]2O
Temperature: 25 °C
Reaction time: 8 h
Yield: 25 %

Procedure:
To a stirred solution of 4-methyltestosterone (500 mg) in MeOH (60 ml) and NaOH 4N (2 ml) at 0° C., 30-32 wt. % H2O2 solution in water (2.0 ml) was added. The suspension was stirred at RT overnight. 10% aqueous Na2SO3 solution (5 ml) was cautiously added dropwise at 0° C. The mixture was saturated with NaCl and extracted three times with EtOAc. The combined organic extracts were dried over Na2SO4, filtered and evaporated to dryness. The crude product was purified by flash chromatography (SiO2, toluene/tert-butyl methyl ether 80/20) to give 4β-methyl-4α,5α-epoxy-17β-hydroxyandrostan-3-one (130 mg, 25%).
Reaction SMILES: [CH3:1][C:2]([CH3:19])([CH2:16][CH2:17][OH:18])[CH2:3][CH2:4][C:5]12[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]1[C:9](=[O:15])[NH:8][C:6]2=[O:7].C(N(CC)CC)C.[CH3:27][S:28](Cl)(=[O:30])=[O:29].C(=O)([O-])O.[Na+]>ClCCl>[CH3:1][C:2]([CH3:19])([CH2:16][CH2:17][O:18][S:28]([CH3:27])(=[O:30])=[O:29])[CH2:3][CH2:4][C:5]12[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]1[C:9](=[O:15])[NH:8][C:6]2=[O:7]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(CCO)CCC12C=CC=CC1C(=O)NC2=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(CCOS(C)(=O)=O)CCC12C=CC=CC1C(=O)NC2=O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 1.57 g (6.0 mmol) of 1-(3,3-dimethyl-5-hydroxypentyl)phthalimide and 0.92 ml (6.6 mmol) of triethylamine in 30 ml of dichloromethane was added, at 0C, 0.51 ml (6.6 mmol) of methanesulfonyl chloride. The mixture was stirred for 30 minutes at room temperature, to which was added a saturated aqueous solution of sodium hydrogencarbonate. The mixture was extracted with dichloromethane. The extract was dried, followed by distilling off the solvent to give 1-(3,3-dimethyl-5-methanesulfonyloxypentyl)phthalimide.
Reaction SMILES: C1COCC1.C[O:7][C:8](=O)[C:9]1[CH:18]=[C:17]([O:19][Si:20]([CH:27]([CH3:29])[CH3:28])([CH:24]([CH3:26])[CH3:25])[CH:21]([CH3:23])[CH3:22])[CH:16]=[C:11]([C:12](OC)=[O:13])[CH:10]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>O>[OH:13][CH2:12][C:11]1[CH:10]=[C:9]([CH2:8][OH:7])[CH:18]=[C:17]([O:19][Si:20]([CH:27]([CH3:29])[CH3:28])([CH:24]([CH3:25])[CH3:26])[CH:21]([CH3:23])[CH3:22])[CH:16]=1
Reactant: COC(=O)c1cc(O[Si](C(C)C)(C(C)C)C(C)C)cc(C(=O)OC)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)[Si](Oc1cc(CO)cc(CO)c1)(C(C)C)C(C)C
Temperature: 0 °C
Reaction time: 1 h
Yield: 74.2 %

Procedure:
To a 100 ml THF solution containing 21.53 g of 5-triisopropylsilanyloxyisophthalic acid dimethyl ester there was added 7.1 g of lithium aluminum hydride at 0° C. After stirring at 0° C. for 1 hour, the mixture was stirred at room temperature for 3 hours and 30 minutes. Water and 1N aqueous sodium hydroxide were added to the reaction mixture which was then filtered through celite. The filtrate was extracted with ethyl acetate. The organic layer was then washed with saturated brine and dried over anhydrous sodium sulfate. The desiccating agent was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate-heptane) to give the title compound (13.53 g) as a colorless solid.