Azzindani/Open_Reaction_Data huggingface dataset:
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[O:24][C:25]1[C:26]([O:28][C@H:29]([C@H:32]([CH2:34][OH:35])[OH:33])[C:30]=1[OH:31])=[O:27])(=O)C.C(=O)([O-])[O-].[K+].[K+]>CO.O>[C@@H:6]1([O:24][C:25]2[C:26]([O:28][C@H:29]([C@H:32]([CH2:34][OH:35])[OH:33])[C:30]=2[OH:31])=[O:27])[O:7][C@H:8]([CH2:19][OH:20])[C@@H:9]([OH:15])[C@H:10]([OH:11])[C@H:5]1[OH:4]
Reactant: CC(=O)OC[C@H]1O[C@@H](OC2=C(O)[C@@H]([C@@H](O)CO)OC2=O)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: O=C1O[C@H]([C@@H](O)CO)C(O)=C1O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O
Reaction time: 0.5 h
Yield: 100 %

Procedure:
After dissolving 2-O-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)ascorbic acid (300 mg, 0.6 mmol) in methanol (10 ml), a solution of potassium carbonate (600 mg) in water (9 ml) was added and the mixture was stirred for 30 minutes. The reaction solution was neutralized with IR-120(H+), the resin was filtered off, and washing was performed with methanol and a 50% methanol aqueous solution. The filtrate and washing solution were combined and concentrated, and then water was added and the mixture was lyophilized to obtain 2-O-(β-D-glucopyranosyl)ascorbic acid as amorphous crystals (190 mg; 100% yield).
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].I[CH2:26][CH3:27]>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH:10]([CH2:26][CH3:27])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCI
Reactant: O=C1CCN(Cc2ccccc2)CC1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CCC1CN(Cc2ccccc2)CCC1=O
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 11.7 %

Procedure:
To a −78° C. solution of 1-benzyl-piperidin-4-one (3.79 g, 20 mmol) in anhydrous THF (20 mL) was added lithium hexamethyldisilazide (21 mL, 21 mmol of a 1.0 M solution in THF). After being stirred at −78° C. for 30 min, a solution of iodoethane (1.7 mL, 21 mmol) in THF (5 mL) was added to the reaction mixture. The resultant solution was stirred at 25° C. for 2 h and quenched with water. The aqueous layer was extracted with CH2Cl2. The organic extracts were combined, washed with brine and dried over MgSO4. The solution was filtered and concentrated in vacuo to give the crude product. The crude material was purified by flash column chromatography (hexane/EtOAc) to provide 0.51 g (11.5% yield) of 1-benzyl-3-ethyl-piperidin-4-one, which was converted into 1-benzyl-3-ethyl-piperidin-4-ylamine (3) using the same procedure as in Scheme 1-1. ((±)-cis:(±)-trans=1:1) LCMS m/z: 219 (M+H)+. This material was used without further purification.
Reaction SMILES: Cl[C:2]1[C:3]2[S:22][CH2:21][CH2:20][C:4]=2[N:5]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)[N:7]=1.[C:23]1([NH2:29])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>O>[CH:23]1([NH:29][C:2]2[C:3]3[S:22][CH2:21][CH2:20][C:4]=3[N:5]=[C:6]([N:8]3[CH2:13][CH2:12][N:11]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[CH2:10][CH2:9]3)[N:7]=2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1
Reactant: Clc1nc(N2CCN(c3ccccc3)CC2)nc2c1SCC2
Reactant: Nc1ccccc1
Solvent: O
Product: c1ccc(N2CCN(c3nc4c(c(NC5CCCCC5)n3)SCC4)CC2)cc1
Yield: 51 %

Procedure:
0.300 g (0.90 mmol) of 4-chloro-2-(4-phenylpiperazin-1-yl)-6,7-dihydrothieno[3,2-d]pyrimidine (V) and 3 mL of phenylamine are combined, then reacted for 0.3 hours at 130° C. in the microwave. Then the reaction mixture is combined with water and extracted with ethyl acetate. The organic phase is dried and evaporated to dryness. The residue is triturated with diethyl ether and suction filtered. 0.18 g of product I (51%) is obtained (m.p. 174° C.-175° C.). 1H-NMR (400 MHz, DMSO): 8.59 (1H, s); 7.63 (2H, d); 7.31 (2H, t); 7.22 (2H, t); 7.03 (1H, t); 6.99 (2H, d); 6.80 (1H, t); 3.83-3.73 (4H, m); 3.31 (2H, t); 3.23 (4H, m); 3.12 (2H, t).
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[Br:12][C:13]1[CH:14]=[C:15]([C:19]([N:21]2[C:29]3[C:24](=[CH:25][C:26]([F:30])=[CH:27][CH:28]=3)[CH2:23][CH2:22]2)=[O:20])[CH:16]=[N:17][CH:18]=1>C(Cl)Cl>[Br:12][C:13]1[CH:18]=[N+:17]([O-:9])[CH:16]=[C:15]([C:19]([N:21]2[C:29]3[C:24](=[CH:25][C:26]([F:30])=[CH:27][CH:28]=3)[CH2:23][CH2:22]2)=[O:20])[CH:14]=1
Reactant: O=C(c1cncc(Br)c1)N1CCc2cc(F)ccc21
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: O=C(c1cc(Br)c[n+]([O-])c1)N1CCc2cc(F)ccc21
Temperature: 25 °C
Reaction time: 4 h

Procedure:
0.19 g (1.1 mmol) m-chloroperbenzoic acid were added to 0.32 g (0.98 mmol) (5-bromo-pyridin-3-yl)-(5-fluoro-2,3-dihydro-indol-1-yl)-methanone in 5.0 mL DCM and the mixture was stirred for 4 h at RT. In addition, a further 95 mg (0.55 mmol) m-chloroperbenzoic acid were added to the reaction mixture and it was stirred for 48 h at RT. Then the reaction mixture was diluted with DCM and extracted with 1N aqueous sodium hydroxide solution. The organic phase was dried on sodium sulphate, evaporated down and dried under HV.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:18]=[CH:17][C:16]2[C:15](=O)[CH2:14][CH2:13][CH2:12][C:11]=2[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH2:21]([O:28][NH2:29])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>N1C=CC=CC=1>[CH2:21]([O:28][NH:29][CH:15]1[CH2:14][CH2:13][CH2:12][C:11]2[N:10]=[C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:18]=[CH:17][C:16]1=2)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: NOCc1ccccc1
Reactant: O=C1CCCc2nc(OCc3ccccc3)ccc21
Agent: Cl
Solvent: c1ccncc1
Product: c1ccc(CONC2CCCc3nc(OCc4ccccc4)ccc32)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 94.8 %

Procedure:
To the mixture of 2-benzyloxy-7,8-dihydro-6H-quinolin-5-one (37.8 g, 149 mmoL) in pyridine (300 mL) was added O-benzylhydroxylamine hydrochloride (26.2 g, 164 mmoL) and the resulting mixture was stirred at room temperature for 24 h. The reaction was concentrated, diluted with methylene chloride and washed with saturated sodium bicarbonate (×2) and brine (×2). The methylene chloride layer was dried, filtered and concentrated. Purification by column chromatography on silica gel with 5% ethyl acetate in hexane provided the desired product (51.0 g, 96%) as an offwhite solid.
Reaction SMILES: C[O-].[Na+].[SH:4][CH2:5][CH2:6][OH:7].Cl[CH2:9][C:10]#[C:11][CH2:12][C:13]#[C:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].O>CO>[CH2:6]([OH:7])[CH2:5][S:4][CH2:9][C:10]#[C:11][CH2:12][C:13]#[C:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: CCCCCCCCC#CCC#CCCl
Reactant: OCCS
Agent: C[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CCCCCCCCC#CCC#CCSCCO
Reaction time: 0.5 h
Yield: 61 %

Procedure:
1.06 ml of a 30% solution of sodium methoxide in methanol were added dropwise, at room temperature, to a solution of 374 μl of 2-mercaptoethanol in 5 ml of anhydrous methanol, under an inert atmosphere. The mixture was maintained under stirring for 30 min and then added to a solution of 1.2 g of 1-chloro-2,5-tetradecadiyne in 6 ml of methanol, under an inert atmosphere. The mixture was maintained under stirring for 15 hours at room temperature and then the reaction medium was poured over 100 ml of acid water (98 ml of water+2 ml concentrated H2SO4) and then extracted 3 times with ethyl ether. The combined organic phases were washed 3 times with water and then with a saturated aqueous solution of NaCl before being dried (Na2SO4), filtered and concentrated under vacuum in a rotary evaporator. The oil thus obtained crystallized on cooling. It was purified by recrystallization from a heptane/pentane mixture and then from a heptane/pentane/diisopropyl ether mixture. 3-Thia-5,8-heptadecadiyn-1-ol was thus isolated in the form of pale yellow flakes with a yield of 61%.
Reaction SMILES: [C:1]([OH:9])(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].ClCC(OC(=O)CCl)=O.[C:19]([O:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:25][CH:24]=1)(=[O:21])[CH3:20]>ClCC(Cl)(Cl)Cl>[C:19]([O:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][C:32]([C:1](=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7])=[CH:31][CH:30]=2)=[CH:25][CH:24]=1)(=[O:21])[CH3:20]
Reactant: CCCCCCC(=O)O
Reactant: CC(=O)Oc1ccc(-c2ccccc2)cc1
Agent: ClCC(Cl)(Cl)Cl
Agent: O=C(CCl)OC(=O)CCl
Product: CCCCCCC(=O)c1ccc(-c2ccc(OC(C)=O)cc2)cc1
Temperature: 100 °C
Reaction time: 10 h
Yield: 74 %

Procedure:
In 50 ml of tetrachloroethane were dissolved 6.51 g (0.05 mole) of heptanoic acid and 9.83 g (0.0575 mole) of monochloroacetic anhydride. To the resulting solution were added 12.74 g (0.06 mole) of 4-acetoxybiphenyl and 0.8 g of boron trifluoride-diethyl ether complex and the resulting mixture was then stirred at 100° C. for 10 hours. After completion of the reaction, the reaction solution was cooled and washed with 5% aqueous sodium carbonate solution and water in this order. The organic layer was concentrated under reduced pressure to obtain 12.0 g of 4-acetoxy-4'-heptanoylbiphenyl.
Reaction SMILES: Cl[CH2:2][Si:3]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Na].[NH:17]1[CH:21]=[CH:20][N:19]=[CH:18]1.O>CN(C)C=O>[CH3:13][C:12]([CH3:15])([O:11][Si:3]([CH2:2][N:17]1[CH:21]=[CH:20][N:19]=[CH:18]1)([CH3:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH3:14]
Reactant: c1c[nH]cn1
Reactant: CC(C)(C)O[Si](C)(CCl)c1ccccc1
Agent: [Na]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)O[Si](C)(Cn1ccnc1)c1ccccc1
Reaction time: 3 h
Yield: 92.3 %

Procedure:
A mixture of 3.6 g (0.015 mol) of chloromethyl(1,1-dimethylethoxy)methyl(phenyl)silane and 1.3 g (0.015 mol) of imidazole sodium salt in 10 ml of dimethylformamide was stirred at 50° for 3 hours, allowed to stand at room temperature for 72 hours, poured into water, and extracted with ether. The ether extracts were washed three times with water and once with brine, dried over magnesium sulfate, and evaporated to leave 3.8 g of an oil. Impurities were removed by Kugelrohr distillation at 90° (airbath)/0.05 mm to leave 2.9 g (71%) of the title compound as a pale yellow oil: nD20 15291; ir (neat) 3105, 3070, 3045, 2970, 1590, 1500, 1425, 1360, 1250, 1235, 1185, 1110, 1055, 1020, 900, 805, 740, 700, 660 cm-1 ; nmr (CDCl3): 0.6 (3H, s), 1.3 (9H, s), 3.6 (2H, s), 6.8 (1H, s), 7.0 (1H, s) and 7.3-7.7 (6H, m).
Reaction SMILES: [C:1]([NH:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].C([Li])CCC.CON(C)[C:22](=[O:30])[C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1.O>O1CCCC1>[F:29][C:26]1[CH:27]=[CH:28][C:23]([C:22]([C:13]2[CH:12]=[N:11][CH:10]=[CH:9][C:8]=2[NH:7][C:1](=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3])=[O:30])=[CH:24][CH:25]=1
Reactant: CC(C)(C)C(=O)Nc1ccncc1
Reactant: CON(C)C(=O)c1ccc(F)cc1
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)C(=O)Nc1ccncc1C(=O)c1ccc(F)cc1
Temperature: 0 °C
Reaction time: 5 h
Yield: 85.4 %

Procedure:
To a solution of 4-pivaloylaminopyridine (7.0 g, 39 mmol) in tetrahydrofuran (100 ml) was added n-butyllithium (39.3 ml, 98 mmol, 2.5 M solution in tetrahydrofuran) at −78° C. under a N2 atmosphere. The reaction mixture was stirred at 0° C. for 5 h, re-cooled to −78° C. and quenched with a solution of N-methoxy-N-methyl-4-fluorobenzamide (7.9 g, 43 mmol) in 100 ml tetrahydrofuran. The reaction mixture was warmed to room temperature and poured into water. The product was extracted into ethyl acetate. The organic layers were washed with brine, dried over sodium sulfate and evaporated to dryness. The residue was purified by flash chromatography (10% ethyl acetate/hexanes gradient) to afford N-[3-(4-fluorobenzoyl)pyridin-4-yl]-2,2-dimethylpropanamide (10 g).
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[C:4]([NH:17][CH2:18][CH:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:3]=1.[CH3:32][S-:33].[Na+]>CN(C)C=O.O>[C:20]1([CH:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:18][NH:17][C:4]2[N:3]=[C:2]([S:33][CH3:32])[N:10]=[C:9]3[C:5]=2[N:6]=[CH:7][N:8]3[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: C[S-]
Reactant: Clc1nc(NCC(c2ccccc2)c2ccccc2)c2ncn(C3CCCCO3)c2n1
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CSc1nc(NCC(c2ccccc2)c2ccccc2)c2ncn(C3CCCCO3)c2n1
Temperature: 100 °C
Reaction time: 72 h
Yield: 99.8 %

Procedure:
A solution of 2-chloro-N-(2,2-diphenylethyl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (Preparation 2) (49.7 g, 0.11 mol) in dry N,N-dimethylformamide (200 ml) was treated with sodium thiomethoxide (10 g, 0.14 mol) and the resulting mixture heated under an atmosphere of nitrogen at 100° C. for 90 minutes. The mixture was stirred at room temperature for 72 hours and then reheated at 100° C. for a further 2 hours. The reaction mixture was cooled and diluted with water (1000 ml). A suspension was formed which was extracted with diethyl ether (×2). The combined organic layers were washed sequentially with water and brine, dried over anhydrous magnesium sulphate, filtered and the solvent removed under reduced pressure. The residue was azeotroped with diethyl ether followed by pentane to afford the title compound as a foam (48.9 g).
Reaction SMILES: [C:1]([C:3]1[S:4][C:5]([CH3:8])=[CH:6][CH:7]=1)#[CH:2].C(NC(C)C)(C)C.I[C:17]1[CH:22]=[CH:21][C:20](/[C:23](/[C:40]2[CH:45]=[CH:44][C:43]([C:46]([F:49])([F:48])[F:47])=[CH:42][CH:41]=2)=[CH:24]\[CH2:25][O:26][C:27]2[CH:38]=[CH:37][C:30]([O:31][CH2:32][C:33]([O:35][CH3:36])=[O:34])=[C:29]([CH3:39])[CH:28]=2)=[CH:19][CH:18]=1>O1CCCC1.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:39][C:29]1[CH:28]=[C:27]([O:26][CH2:25]/[CH:24]=[C:23](\[C:20]2[CH:19]=[CH:18][C:17]([C:2]#[C:1][C:3]3[S:4][C:5]([CH3:8])=[CH:6][CH:7]=3)=[CH:22][CH:21]=2)/[C:40]2[CH:45]=[CH:44][C:43]([C:46]([F:49])([F:48])[F:47])=[CH:42][CH:41]=2)[CH:38]=[CH:37][C:30]=1[O:31][CH2:32][C:33]([O:35][CH3:36])=[O:34]
Reactant: COC(=O)COc1ccc(OC/C=C(\c2ccc(I)cc2)c2ccc(C(F)(F)F)cc2)cc1C
Reactant: C#Cc1ccc(C)s1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: COC(=O)COc1ccc(OC/C=C(\c2ccc(C#Cc3ccc(C)s3)cc2)c2ccc(C(F)(F)F)cc2)cc1C
Temperature: 25 °C
Reaction time: 19 h

Procedure:
2-Ethynyl-5-methylthiophene (161 mg, 1.32 mmol) and diisopropylamine (0.43 mL, 3.10 mmol) were added to a solution of methyl (Z)-[4-[3-(4-iodophenyl)-3-(4-trifluoromethylphenyl)allyloxy]-2-methylphenoxy]acetate (384 mg, 0.659 mmol; example 4) in tetrahydrofuran (10 mL). The mixture was degassed and copper(I) iodide (10 mg, 0.053 mmol) and bis(triphenylphosphine)palladium(II) dichloride (23 mg, 0.033 mmol) were added. The reaction mixture was stirred at ambient temperature for 19 h and subsequently evaporated in vacuo. The residue was purified by flash column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 15:1-12:1) yielding methyl (E)-[2-methyl-4-[3-[4-[(5-methylthiophen-2-yl)ethynyl]phenyl]-3-(4-trifluoromethylphenyl)allyloxy]phenoxy]acetate as brown oil.
Reaction SMILES: ClC(Cl)(OC(=O)[O:6][C:7]([Cl:10])(Cl)Cl)Cl.[Cl:13][C:14]1[CH:15]=[C:16]([CH:21]2[CH:25]([CH:26]([O:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=3)[CH3:27])[CH2:24][NH:23][CH2:22]2)[CH:17]=[CH:18][C:19]=1[Cl:20].N1C=CC=CC=1>C(Cl)Cl>[Cl:13][C:14]1[CH:15]=[C:16]([CH:21]2[CH:25]([CH:26]([O:28][C:29]3[CH:30]=[CH:31][C:32]([C:35]([F:37])([F:38])[F:36])=[CH:33][CH:34]=3)[CH3:27])[CH2:24][N:23]([C:7]([Cl:10])=[O:6])[CH2:22]2)[CH:17]=[CH:18][C:19]=1[Cl:20]
Reactant: CC(Oc1ccc(C(F)(F)F)cc1)C1CNCC1c1ccc(Cl)c(Cl)c1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(Oc1ccc(C(F)(F)F)cc1)C1CN(C(=O)Cl)CC1c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Yield: 126.8 %

Procedure:
To a stirred solution of carbonic acid ditrichloromethyl ester (triphosgene) (29 mg, 0.098 mmol) in CH2Cl2 (2 mL) at −78° C., was added a solution of (3RS,4SR)-3-(3,4-dichloro-phenyl)-4-[(RS)-1-(4-trifluoromethyl-phenoxy)-ethyl]-pyrrolidine (intermediate XV-B-1) (100 mg, 0.25 mmol) and pyridine (0.043 mL, 0.54 mmol) in CH2Cl2 (2 mL) over 30 minutes. The temperature was raised to RT, and stirring was continued over night. The organic phase was washed with H2O, dried over Na2SO4. Concentration under vacuo yielded 58 mg (50%) of the title compound as a light yellow solid.
Reaction SMILES: I([O-])(=O)(=O)=[O:2].[Na+].[CH3:7][CH:8]([C@@H:17]1[C@:34]2([CH3:35])[C@H:20]([C:21]3[C@H:31]([CH2:32][CH2:33]2)[C@:29]2([CH3:30])[C:24]([CH2:25][C@@H:26]([O:41][C:42]([O:44][CH3:45])=[O:43])[CH2:27][C@@H:28]2[O:36][C:37]([O:39][CH3:40])=[O:38])=[CH:23][CH:22]=3)[CH2:19][CH2:18]1)[CH2:9][S:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>O1CCCC1.C(OCC)C>[CH3:7][CH:8]([C@@H:17]1[C@:34]2([CH3:35])[C@H:20]([C:21]3[C@H:31]([CH2:32][CH2:33]2)[C@:29]2([CH3:30])[C:24]([CH2:25][C@@H:26]([O:41][C:42]([O:44][CH3:45])=[O:43])[CH2:27][C@@H:28]2[O:36][C:37]([O:39][CH3:40])=[O:38])=[CH:23][CH:22]=3)[CH2:19][CH2:18]1)[CH2:9][S:10]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:2]
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: COC(=O)O[C@@H]1CC2=CC=C3[C@@H]4CC[C@H](C(C)CSc5ccccc5)[C@@]4(C)CC[C@@H]3[C@@]2(C)[C@@H](OC(=O)OC)C1
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: COC(=O)O[C@@H]1CC2=CC=C3[C@@H]4CC[C@H](C(C)CS(=O)c5ccccc5)[C@@]4(C)CC[C@@H]3[C@@]2(C)[C@@H](OC(=O)OC)C1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 68.7 %

Procedure:
To a solution of 20 mg of sodium metaperiodate in 2 ml of tetrahydrofuran was added dropwise an ice-cooled solution of 41 mg of 20-methyl-1α,3β-bis(methoxycarbonyloxy)-21-phenylthiopregna-5,7-diene in 1 ml of diethyl ether. The resulting mixture was stirred with ice cooling for 30 minutes, then the insoluble matter was filtered off and washed with diethyl ether, and the filtrate and washings were combined, washed in sequence with an aqueous solution of sodium thiosulfate, water, an aqueous solution of sodium hydrogen carbonate and an aqueous solution of sodium chloride, then dried and concentrated. The residue was purified by silica gel column chromatography to give 29 mg of 20-methyl-1α,3β-bis(methoxycarbonyloxy)-21-phenylsulfinylpregna-5,7 -diene.
Reaction SMILES: [C:1]([C:5]1[CH:20]=[CH:19][CH:18]=[CH:17][C:6]=1[O:7][C:8]1[C:13]([N+:14]([O-])=O)=[CH:12][CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2]>CO.C(OCC)(=O)C.[Pd]>[C:1]([C:5]1[CH:20]=[CH:19][CH:18]=[CH:17][C:6]=1[O:7][C:8]1[C:13]([NH2:14])=[CH:12][CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1ccccc1Oc1ncccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CO
Product: CC(C)(C)c1ccccc1Oc1ncccc1N
Reaction time: 8 h
Yield: 112.1 %

Procedure:
1a (7.2 g, 26.5 mmol) was dissolved in a 1:1 mixture of methanol and ethyl acetate (160 mL). Palladium on charcoal (10%, 360 mg, 0.33 mmol) was added, and the mixture was stirred overnight under hydrogen atmosphere. The reaction mixture was filtered over Celite® and concentrated to afford 7.2 g (100%) of 1b as a white powder. [M+H]+=243.3.
Reaction SMILES: [CH2:1]([O:3][CH2:4][CH2:5][N:6]=[C:7]=[O:8])[CH3:2].[F:9][C:10]1[C:11](=[O:17])[NH:12][C:13](=[O:16])[NH:14][CH:15]=1>CN(C)C(=O)C.C(OCC)(=O)C>[CH2:1]([O:3][CH2:4][CH2:5][NH:6][C:7]([N:14]1[CH:15]=[C:10]([F:9])[C:11](=[O:17])[NH:12][C:13]1=[O:16])=[O:8])[CH3:2]
Reactant: CCOCCN=C=O
Reactant: O=c1[nH]cc(F)c(=O)[nH]1
Solvent: CCOC(C)=O
Solvent: CC(=O)N(C)C
Product: CCOCCNC(=O)n1cc(F)c(=O)[nH]c1=O
Reaction time: 3 h

Procedure:
To the above solution of 2-ethoxyethyl isocyanate was added a solution of 5-fluorouracil (2.60 g.) in N,N-dimethylacetamide (20 ml.) at 80° and stirred for further 3 hours at the same temperature. The resultant mixture was diluted with ethyl acetate (200 ml.), washed with saturated sodium chloride aqueous solution (each 30 ml., 2 times), dried over magnesium sulfate, treated with activated charcoal, filtered and evaporated in vacuo. The residue was recrystallized from ethyl acetate to give 1-[N-(2-ethoxyethyl)carbamoyl]-5-fluorouracil (1.82 g.).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.[N+:9]([C:12]1[CH:17]=[CH:16][C:15]([S:18](Cl)(=[O:20])=[O:19])=[CH:14][CH:13]=1)([O-:11])=[O:10].C(O)(=O)C>N1C=CC=CC=1>[N+:9]([C:12]1[CH:13]=[CH:14][C:15]([S:18]([NH:1][C:2]2[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=2)(=[O:20])=[O:19])=[CH:16][CH:17]=1)([O-:11])=[O:10]
Reactant: Nc1cccc(O)c1
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Solvent: CC(=O)O
Product: O=[N+]([O-])c1ccc(S(=O)(=O)Nc2cccc(O)c2)cc1
Yield: 56.6 %

Procedure:
A mixture of 3-aminophenol (33 g, 0.3 mole) and p-nitrobenzenesulfonyl chloride (66 g, 0.3 mole) in pyridine (350 ml) was heated at 80° on a steam bath for 4 hours. The reaction mixture was poured on ice and acidified with acetic acid. The precipitated product was filtered and recrystallized from isopropanol and gave 50 g (49%) of product which was used in Part B.
Reaction SMILES: [C:1]([CH:3]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]1)#[N:2].[CH3:14][Si]([N-][Si](C)(C)C)(C)C.[Li+].IC>C1COCC1>[C:10]([O:9][C:7]([N:5]1[CH2:6][C:3]([C:1]#[N:2])([CH3:14])[CH2:4]1)=[O:8])([CH3:13])([CH3:12])[CH3:11]
Reactant: CC(C)(C)OC(=O)N1CC(C#N)C1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CI
Product: CC1(C#N)CN(C(=O)OC(C)(C)C)C1
Temperature: -76 °C
Reaction time: 0.5 h
Yield: 89.5 %

Procedure:
In a 100 mL 2-neck round-bottomed flask, tert-butyl 3-cyanoazetidine-1-carboxylate (1.5 g, 8.2 mmol) was dissolved in THF (30 mL). The colorless solution was cooled to −76° C. and lithium bis(trimethylsilyl)amide (1.0M solution in THF, 9.0 mL, 9.0 mmol) was added dropwise over 25 min. The yellow solution was stirred at −76° C. for 30 min then iodomethane (0.78 mL, 12.5 mmol) was slowly added. The reaction mixture was stirred at −76° C. for 30 min and then warmed to room temperature over 1 h. The reaction mixture was quenched with 10 mL of saturated NH4Cl and diluted with 10 mL of water then extracted with ˜100 ml EtOAc (2×). The combined organic layers were washed with ˜10 mL water and ˜10 mL brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over 40 g silica gel with EtOAc/hexanes, (gradient: 0-30% EtOAc). All fractions containing product were combined and concentrated to afford 1.44 g (89%) of 3-cyano-3-methyl-azetidine-1-carboxylic acid tert-butyl ester as a yellow solid.
Reaction SMILES: CS(C)=O.[H-].[Na+].[N+:7]([CH3:10])([O-:9])=[O:8].C([C:13]([O:15][CH2:16][CH3:17])=[O:14])#N>C(O)(=O)C>[N+:7]([CH2:10][C:13]([O:15][CH2:16][CH3:17])=[O:14])([O-:9])=[O:8]
Reactant: CCOC(=O)C#N
Reactant: C[N+](=O)[O-]
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CS(C)=O
Product: CCOC(=O)C[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 2 h
Yield: 83 %

Procedure:
To a 100 ml three-neck round bottom flask, equipped with an addition funnel, a thermometer and a condenser topped with a nitrogen gas inlet tube, was added 20 ml of dimethylsulfoxide, 0.196 g (0.00815 mole) sodium hydride and then 0.5 g (0.00815 mole) of nitromethane was added dropwise at ambient temperature to give a slurry. 1.6 ml (0.0163 mole) of ethyl cyanoformate was then added dropwise forming a homogeneous solution and was then stirred for 2 hours at ambient temperature. The solution was made acidic by adding 30 ml of 1 Normal acetic acid with stirring. The product was extracted with ethyl acetate and dried over magnesium sulfate. Ethyl nitroacetate was formed in 83% yield as determined by gas chromatography.