Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]=[C:2]([OH:14])[C@@H:3]([C@H:5]([C@@H:7]([C@@H:9]([C:11]([O-:13])=[O:12])[OH:10])O)[OH:6])[OH:4].[K+].[CH3:16][O-].[Na+]>>[CH3:16][O:13][C:11]([C@@H:9]([OH:10])[C@H:7]1[O:14][C:2](=[O:1])[C@H:3]([OH:4])[C@H:5]1[OH:6])=[O:12]
Reactant: O=C([O-])[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(=O)O
Reactant: C[O-]
Agent: [K+]
Agent: [Na+]
Product: COC(=O)[C@@H](O)[C@H]1OC(=O)[C@H](O)[C@H]1O

Procedure:
Monopotassium D-glucarate and sodium methoxide solution (NaOMe) (0.5 M in methanol) were commercial products. Methyl D-glucarate 1,4-lactone was prepared as previously described (Kiely, 1994). Some carbohydrate diacids and diamines or polyamines were prepared as needed. Other commercial chemicals and solvents were used without further purification. Solutions were concentrated in vacuo (15-20 mbar) using a rotary evaporator and water bath at 30° C. pH was estimated using pHydrion paper produced by Micro Essential Laboratory (Brooklyn, N.Y., USA).
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([C:9]([N:11]2[CH2:16][CH2:15][N:14]([C:17]3[C:22]([CH3:23])=[CH:21][C:20]([CH3:24])=[C:19]([CH3:25])[N:18]=3)[CH2:13][CH2:12]2)=[O:10])=[CH:4][CH:3]=1.[CH3:26][CH:27]1[NH:31][C:30](=[O:32])[CH2:29][CH2:28]1>>[CH3:26][CH:27]1[N:31]([C:2]2[CH:3]=[CH:4][C:5]([C:9]([N:11]3[CH2:16][CH2:15][N:14]([C:17]4[C:22]([CH3:23])=[CH:21][C:20]([CH3:24])=[C:19]([CH3:25])[N:18]=4)[CH2:13][CH2:12]3)=[O:10])=[C:6]([CH3:8])[N:7]=2)[C:30](=[O:32])[CH2:29][CH2:28]1
Reactant: CC1CCC(=O)N1
Reactant: Cc1cc(C)c(N2CCN(C(=O)c3ccc(Br)nc3C)CC2)nc1C
Product: Cc1cc(C)c(N2CCN(C(=O)c3ccc(N4C(=O)CCC4C)nc3C)CC2)nc1C
Yield: 85.8 %

Procedure:
Using (6-bromo-2-methylpyridin-3-yl)[4-(3,5,6-trimethylpyridin-2-yl)piperazin-1-yl]methanone (145 mg) described in Preparation Example 248 and 5-methylpyrrolidin-2-one (54 mg) and by the reaction and treatment in the same manner as in Example 262, the title compound (130 mg) was obtained.
Reaction SMILES: [CH:1]1([C:4]2[CH:5]=[CH:6][C:7]([C:15]([OH:17])=O)=[N:8][C:9]=2[O:10][CH2:11][CH:12]2[CH2:14][CH2:13]2)[CH2:3][CH2:2]1.Cl.[NH2:19][C:20]([C:23]1[N:27]=[C:26]([NH2:28])[O:25][N:24]=1)([CH3:22])[CH3:21]>>[NH2:28][C:26]1[O:25][N:24]=[C:23]([C:20]([NH:19][C:15]([C:7]2[CH:6]=[CH:5][C:4]([CH:1]3[CH2:2][CH2:3]3)=[C:9]([O:10][CH2:11][CH:12]3[CH2:13][CH2:14]3)[N:8]=2)=[O:17])([CH3:22])[CH3:21])[N:27]=1
Reactant: O=C(O)c1ccc(C2CC2)c(OCC2CC2)n1
Reactant: CC(C)(N)c1noc(N)n1
Agent: Cl
Product: CC(C)(NC(=O)c1ccc(C2CC2)c(OCC2CC2)n1)c1noc(N)n1

Procedure:
The title compound was synthesized in analogy to Example 1, using 5-cyclopropyl-6-cyclopropylmethyloxy-pyridine-2-carboxylic acid (Example 42a) and 3-(1-amino-1-methyl-ethyl)-[1,2,4]oxadiazol-5-ylamine hydrochloride (1:1) (Example 296b) as starting materials, LC-MS (UV peak area/ESI) 98%, 358.1879 (M+H)+.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([C:10]2[CH:15]=[C:14]([S:16]([CH3:19])(=[O:18])=[O:17])[CH:13]=[CH:12][C:11]=2[O:20][CH:21]([CH3:23])[CH3:22])=[O:9])[CH2:4][CH2:3]1.[N+:24]([C:27]1[CH:32]=[CH:31][C:30](O)=[CH:29][CH:28]=1)([O-:26])=[O:25].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>O1CCCC1>[CH:21]([O:20][C:11]1[CH:12]=[CH:13][C:14]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:15][C:10]=1[C:8]([N:5]1[CH2:4][CH2:3][CH:2]([O:1][C:30]2[CH:31]=[CH:32][C:27]([N+:24]([O-:26])=[O:25])=[CH:28][CH:29]=2)[CH2:7][CH2:6]1)=[O:9])([CH3:23])[CH3:22]
Reactant: CC(C)Oc1ccc(S(C)(=O)=O)cc1C(=O)N1CCC(O)CC1
Reactant: O=[N+]([O-])c1ccc(O)cc1
Agent: CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)Oc1ccc(S(C)(=O)=O)cc1C(=O)N1CCC(Oc2ccc([N+](=O)[O-])cc2)CC1
Temperature: 50 °C
Reaction time: 16 h
Yield: 27 %

Procedure:
To a solution of 0.15 mmol (4-hydroxy-piperidin-1-yl)-(2-isopropoxy-5-methanesulfonyl-phenyl)-methanone (Example 3(a)) in 3 ml tetrahydrofuran were added successively 0.18 mmol 4-nitrophenol, 0.18 mmol triphenylphosphine and 0.18 mmol di-tert-butyl azodicarboxylate. The reaction mixture was stirred at 50° C. for 16 h and was then cooled to room temperature and concentrated in vacuo. The crude material was purified by reversed phase HPLC (acetonitrile/water) to afford the title compound as a white crystalline solid (yield 27%). MS (m/e): 463.4 (M+H+, 100%).
Reaction SMILES: [C:1](Cl)(=[O:5])[C:2]([CH3:4])=[CH2:3].[OH:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][N:14]1[C:26]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[C:20]2[C:15]1=[CH:16][CH:17]=[CH:18][CH:19]=2.C(N(CC)CC)C>ClCCl>[C:1]([O:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][N:14]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=2[C:21]2[C:26]1=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:5])[C:2]([CH3:4])=[CH2:3]
Reactant: C=C(C)C(=O)Cl
Reactant: OCCCCCCn1c2ccccc2c2ccccc21
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C=C(C)C(=O)OCCCCCCn1c2ccccc2c2ccccc21
Temperature: 25 °C
Reaction time: 3 h
Yield: 70 %

Procedure:
A solution of 30 mmol of methacryloyl chloride in 10 ml of dichloromethane was added dropwise to a solution of 25 mmol of N-(6-hydroxyhexyl)-carbazole and 30 mmol of triethylamine in 100 ml of dry dichloromethane. Thereafter, the reaction mixture was stirred for 3 hours at room temperature and then worked up by washing it with 2N sodium hydroxide solution and water. After the reaction mixture had been evaporated down, the 6-(N-carbazolyl)-hexyl methacrylate formed was isolated by column chromatography over silica gel (eluent: dichloromethane). The 6-(N-carbazolyl)-hexyl methacrylate thus obtained in 70% yield was in the form of a colorless oil and had the following characteristic data:
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:23]([CH:25]2[CH2:27][CH2:26]2)O)[N:12]=[N:13][C:14]=1[O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O>ClCCl>[CH2:16]([O:15][C:14]1[N:13]=[N:12][C:11]([CH:23]=[C:25]2[CH2:27][CH2:26]2)=[CH:10][C:9]=1[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: OC(c1cc(OCc2ccccc2)c(OCc2ccccc2)nn1)C1CC1
Agent: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C(=C1CC1)c1cc(OCc2ccccc2)c(OCc2ccccc2)nn1
Temperature: 2.5 °C
Reaction time: 3 h
Yield: 55.6 %

Procedure:
(5,6-bis(Benzyloxy)pyridazin-3-yl)(cyclopropyl)methanol (Intermediate 64, 0.34 g, 0.94 mmol) was dissolved in dichloromethane (10.2 ml) and cooled at 0-5° C. under nitrogen atmosphere. Triethylamine (0.474 g, 4.70 mmol) and methanesulfonylchloride (0.162 g, 1.401 mmol) were added to the reaction and it was allowed to stir at room temperature for 3 hours. Upon completion the reaction was quenched by pouring into saturated aqueous sodium bicarbonate solution (25 ml) and the product was extracted into ethyl acetate (2×50 ml). The combined organics were separated, washed with brine, dried (Na2SO4) and concentrated in vacuo. The crude compound was purified by column chromatography (silica, 0-10% ethyl acetate in n-hexane) to afford 3,4-bis(benzyloxy)-6-(cyclopropylidenemethyl)pyridazine (0.18 g, 56% yield).
Reaction SMILES: [N:1]([C@H:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][C@@H:5]1[OH:17])=[N+]=[N-].[H][H]>CO.[OH-].[Pd+2].[OH-]>[NH2:1][C@@H:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])[CH2:6][C@H:5]1[OH:17]
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)N1CC[C@H](N=[N+]=[N-])[C@@H](O)C1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CC[C@@H](N)[C@H](O)C1
Reaction time: 72 h

Procedure:
(3S*,4S*)-tert-butyl 4-azido-3-hydroxypiperidine-1-carboxylate from example C1 (47 g, 194 mmol) is dissolved in methanol (1200 mL) under nitrogen. Palladium hydroxide (20% on carbon; 4.7 g) is added. The atmosphere is changed to hydrogen and the stirred reaction mixture is hydrogenated at room temperature and 70 psi for 72 hours. The mixture is filtered through celite. The filtrate is evaporated. The residue is recrystallized from CH2Cl2 with a small amount of MeOH to obtain the title compound as a white solid.
Reaction SMILES: [OH:1][CH2:2][C:3]([CH3:22])([CH3:21])[CH2:4][CH2:5][CH2:6][C:7](=[O:20])[CH2:8][CH2:9][CH2:10][CH2:11][C:12]([CH3:19])([CH3:18])[C:13]([O:15][CH2:16][CH3:17])=[O:14].[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=[O:24].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>CN(C=O)C.S(=O)(=O)(O)O.O>[CH2:16]([O:15][C:13](=[O:14])[C:12]([CH3:19])([CH3:18])[CH2:11][CH2:10][CH2:9][CH2:8][C:7](=[O:20])[CH2:6][CH2:5][CH2:4][C:3]([CH3:21])([CH3:22])[C:2]([OH:24])=[O:1])[CH3:17]
Reactant: CCOC(=O)C(C)(C)CCCCC(=O)CCCC(C)(C)CO
Reactant: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: O=S(=O)(O)O
Agent: c1cc[nH+]cc1
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)C(C)(C)CCCCC(=O)CCCC(C)(C)C(=O)O
Temperature: 25 °C
Reaction time: 46 h
Yield: 81.9 %

Procedure:
A mixture of ethyl 12-hydroxy-2,2,11,11-tetramethyl-7-oxo-dodecanoate (3.26 g, 10 mmol) and pyridinium dichromate (14.0 g, 36 mmol) in DMF (45 mL) was stirred at room temperature for 46 h. The solution was diluted with 48% aqueous sulfuric acid (30 mL) and water (300 mL). The product was extracted with ethyl acetate (5×100 mL). The combined organic layers were washed with saturated NaCl solution (5×100 mL), dried over MgSO4, and concentrated to give the crude product (3.19 g) as a green oil. The crude product (3.1 g) was subjected to column chromatography on silica gel eluting with hexanes/ethyl acetate (3:1, then 2:1) to give pure 2,2,11,11-tetramethyl-7-oxo-dodecanedioic acid 1-ethyl ester (2.69 g, 82%) as a pale yellow oil. 1H NMR (300 MHz, CDCl3/TMS): δ (ppm): 11.30 (br. s, 1 H), 4.10 (q, 2 H, J=7.2 Hz), 2.39 (t, 4 H, J=7.2 Hz), 1.56-1.48 (m, 8 H), 1.24 (t, 5H, J=7.2 Hz), 1.20 (s, 6 H), 1.15 (s, 6 H). 13C NMR (75 MHz, CDCl3/TMS): δ (ppm): 210.9, 184.4, 178.1, 60.4, 43.1, 42.7, 42.2, 40.5, 39.8, 25.3, 25.0, 24.7, 24.3, 19.3, 14.4. HRMS (LSIMS, gly): Calcd. for C18H33O5 (MH+): 329.2328, found: 329.2330.
Reaction SMILES: [CH2:1]1[C@@H:11]2[C@H:5]([CH:6]=[CH:7][C:8]3[C:9]4[N:10]2[C:12]2[CH:21]=[CH:20][N:19]=[CH:18][C:13]=2[C:14]=4[CH2:15][CH2:16][CH:17]=3)[CH2:4][CH2:3][CH2:2]1.[I-].[K+].C(N(CC)CC)C.Cl[CH2:32][CH2:33][C:34]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:35]>CN(C=O)C>[CH2:1]1[CH:11]2[CH:5]([CH:6]=[CH:7][C:8]3[C:9]4[N:10]2[C:12]2[CH:21]=[CH:20][N:19]=[CH:18][C:13]=2[C:14]=4[CH2:15][CH2:16][CH:17]=3)[CH2:4][CH:3]([CH2:32][CH2:33][C:34]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[O:35])[CH2:2]1
Reactant: O=C(CCCl)c1ccccc1
Reactant: C1=C[C@@H]2CCCC[C@H]2n2c3c(c4cnccc42)CCC=C13
Agent: [I-]
Agent: [K+]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: O=C(CCC1CCC2C(C=CC3=CCCc4c3n2c2ccncc42)C1)c1ccccc1
Temperature: 60 °C
Yield: 82.4 %

Procedure:
5.5 grams of (±)-trans-1,2,3,4,4a,8,9,14a-octahydropyrido[4',3':2,3]indolo[1,7-ab][1]benzazepine, 3.6 grams of potassium iodide, 6.5 ml of triethylamine and 4.2 grams of β-chloropropiophenone were suspended in 100 ml DMF and heated to 60° C for 2 hours. The mixture was permitted to cool to room temperature, poured into 200 ml. of water and extracted with benzene. The benzene layer was washed with water, dried over potassium carbonate, filtered and evaporated to dryness in vacuo. The resulting oil was taken up in ether and converted to the hydrochloride salt as in Example 7, thus yielding 6.7 grams of the title compound, hydrochloride salt, m.p. 279° C (dec).
Reaction SMILES: [C:1]([CH2:4]P(=O)(OCC)OCC)(=[O:3])[NH2:2].CC(C)([O-])C.[K+].[CH2:19]([O:22][C:23]([N:25]1[CH2:29][C@H:28]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[CH2:27][C@H:26]1[CH2:38][CH2:39][N:40]1[CH:44]=[C:43]([CH:45]=O)[N:42]=[CH:41]1)=[O:24])[CH:20]=[CH2:21]>O1CCCC1.C(OCC)(=O)C.O>[CH2:19]([O:22][C:23]([N:25]1[CH2:29][C@H:28]([O:30][Si:31]([C:34]([CH3:36])([CH3:37])[CH3:35])([CH3:33])[CH3:32])[CH2:27][C@H:26]1[CH2:38][CH2:39][N:40]1[CH:44]=[C:43]([CH:45]=[CH:4][C:1](=[O:3])[NH2:2])[N:42]=[CH:41]1)=[O:24])[CH:20]=[CH2:21]
Reactant: C=CCOC(=O)N1C[C@H](O[Si](C)(C)C(C)(C)C)C[C@H]1CCn1cnc(C=O)c1
Reactant: CCOP(=O)(CC(N)=O)OCC
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: C=CCOC(=O)N1C[C@H](O[Si](C)(C)C(C)(C)C)C[C@H]1CCn1cnc(C=CC(N)=O)c1
Reaction time: 1 h
Yield: 52.5 %

Procedure:
To a solution of diethyl carbamoylmethylphosphonate (12.7 g) and potassium tert-butoxide (13.9 g) in tetrahydrofuran (400 ml) were added a solution of (2R,4R)-1-allyloxycarbonyl-4-tert-butyldimethylsilyloxy-2-{2-(4-formylimidazol-1-yl)ethyl}pyrrolidine (24 g) in tetrahydrofuran (50 ml) at 45° C. After stirring for 1 hour, to the reaction mixture were added water (3 ml). Evaporation of the solvent gave a residue, which was dissolved in a mixture of ethyl acetate (500 ml) and water (50 ml). The organic layer was separated, washed in turn with water (50 ml×2) and brine (50 ml×2), and dried over magnesium sulfate. Evaporation of the solvent gave an oil, which was chromatographed on silica gel (500 ml) eluting with a mixture of dichloromethane and methanol (10:1) to give (2R,4R)-1-allyloxycarbonyl-4-tert-butyl-dimethylsilyloxy-2-[2-{4-(2-carbamoylethenyl)imidazol-1-yl}ethyl]pyrrolidine (13.87 g).
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[Cl:8][C:9]1[C:24]([Cl:25])=[CH:23][C:12]2[C:13](=O)[CH2:14][C:15]3[CH:21]=[CH:20][CH:19]=[CH:18][C:16]=3[S:17][C:11]=2[CH:10]=1.O>C1C=CC=CC=1.[Ti](Cl)(Cl)(Cl)Cl>[Cl:8][C:9]1[C:24]([Cl:25])=[CH:23][C:12]2[C:13]([N:5]3[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]3)=[CH:14][C:15]3[CH:21]=[CH:20][CH:19]=[CH:18][C:16]=3[S:17][C:11]=2[CH:10]=1
Reactant: CN1CCNCC1
Reactant: O=C1Cc2ccccc2Sc2cc(Cl)c(Cl)cc21
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: O
Solvent: c1ccccc1
Product: CN1CCN(C2=Cc3ccccc3Sc3cc(Cl)c(Cl)cc32)CC1
Reaction time: 28 h

Procedure:
1-Methylpiperazine (15.0 g), followed by titanium tetrachloride (3.1 g) in benzene (45 ml), was added to a warm solution of 7,8-dichlorodibenzo(b,f)thiepine-10(11H)-one (8.85 g) (its preparation is described in Example 8) in benzene (75 ml). The mixture was refluxed while stirring for 28 hours, cooled and decomposed with water (100 ml). The resultant precipitate was filtered and washed with benzene and water. The benzene layer in the filtrate was separated, washed with water, dried over magnesium sulfate and taken down. The enamine base, obtained in nearly quantitative yield, was purified by crystallization from ethanol, m.p. 157°-159° C. Neutralization with maleic acid in ethanol yields the maleate, C23H22Cl2N2O4S, which is crystallized from ethanol; m.p. 229°-232° C.
Reaction SMILES: [CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:19]2[O:23][N:22]=[C:21]([CH2:24]OS(C3C=CC(C)=CC=3)(=O)=O)[N:20]=2)[CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:36]1([NH2:39])[CH2:38][CH2:37]1>>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:19]2[O:23][N:22]=[C:21]([CH2:24][NH:39][CH:36]3[CH2:38][CH2:37]3)[N:20]=2)[CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:16])[CH3:17])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Cc1ccc(S(=O)(=O)OCc2noc([C@H](CCCC3CCCCC3)CC(=O)OC(C)(C)C)n2)cc1
Reactant: NC1CC1
Product: CC(C)(C)OC(=O)C[C@@H](CCCC1CCCCC1)c1nc(CNC2CC2)no1

Procedure:
Method as for preparation 5 using tert-butyl(3R)-6-cyclohexyl-3-[3-({[(4-methylphenyl)sulfonyl]oxy}methyl)-1,2,4-oxadiazol-5-yl]hexanoate (preparation 177) (500 mg, 0.99 mmol) and cyclopropylamine (210 μl, 2.96 mmol) as starting materials.
Reaction SMILES: COC1C=CC(C[N:8]([C@@H:12]([C@H:27]([O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:13][CH2:14][C:15](=O)[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=2)C(=O)[O-])=CC=1.C(O)(C(F)(F)F)=O.C([BH3-])#N.[Na+]>C(Cl)Cl>[Si:35]([O:34][C@H:27]([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C@H:12]1[CH2:13][CH2:14][C@@H:15]([CH2:16][C:17]2[CH:18]=[CH:19][C:20]([N+:23]([O-:25])=[O:24])=[CH:21][CH:22]=2)[NH:8]1)([C:38]([CH3:40])([CH3:41])[CH3:39])([CH3:36])[CH3:37].[Si:35]([O:34][C@H:27]([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C@H:12]1[CH2:13][CH2:14][C@H:15]([CH2:16][C:17]2[CH:18]=[CH:19][C:20]([N+:23]([O-:25])=[O:24])=[CH:21][CH:22]=2)[NH:8]1)([C:38]([CH3:40])([CH3:41])[CH3:39])([CH3:36])[CH3:37]
Reactant: COc1ccc(CN(C(=O)[O-])[C@H](CCC(=O)Cc2ccc([N+](=O)[O-])cc2)[C@H](O[Si](C)(C)C(C)(C)C)c2ccccc2)cc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(C)[Si](C)(C)O[C@H](c1ccccc1)[C@H]1CC[C@@H](Cc2ccc([N+](=O)[O-])cc2)N1
Product: CC(C)(C)[Si](C)(C)O[C@H](c1ccccc1)[C@H]1CC[C@H](Cc2ccc([N+](=O)[O-])cc2)N1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 26 %

Procedure:
To a solution of MOZ protected ketone amine (from Step G, 34 g, 56 mmol) in DCM (350 ml) was added TFA (256 ml) and the resulting mixture stirred at room temperature for 1.5 h. The solution was evaporated under vacuum and residue partitioned between DCM and sat. NaHCO3. The organic layer was dried over MgSO4, filtered and evaported. The residue was dissolved in MeOH (750 ml) and cooled to 0° C. via ice/water bath. Sodium cyanoborohydride (21.2 g, 337 mmol) was then added and the resulting mixture was stirred overnight to allow to warm to room temperature. The mixture was quenched by addition of water and the organics removed under vacuum. The aqueous layer was then extracted with EtOAc (×2) and the combined EtOAc layers washed with sat. NaCl, dried over MgSO4, filtered and evaporated under vacuum. The residue was purified by column chromatography on silica (eluent: gradient rising from 100% Hexanes to 35% EtOAc in Hexanes) to give 16.4 g (63.4%) of the first isomer, (2R,5S)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-5-(4-nitrobenzyl)pyrrolidine, and 3.1 g (12%) of the second isomer (2R,5R)-2-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-5-(4-nitrobenzyl)pyrrolidine.
Reaction SMILES: CS(C)=O.[CH2:5]([N:12]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH:13]1[CH2:18][CH2:17][CH:16]([OH:19])[CH2:15][CH2:14]1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.CCN(CC)CC>C(Cl)Cl>[CH2:20]([N:12]([CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH:13]1[CH2:14][CH2:15][C:16](=[O:19])[CH2:17][CH2:18]1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: OC1CCC(N(Cc2ccccc2)Cc2ccccc2)CC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: O=C1CCC(N(Cc2ccccc2)Cc2ccccc2)CC1
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
To a solution of oxalylic acid (2.03 mL, 20.31 mmol) in DCM (80 mL) at −60° C. was added dropwise DMSO (3.46 mL, 48.8 mmol). After stirring for 5 min, a solution of 4-(dibenzylamino)cyclohexanol (6 g, 20.31 mmol) in DCM (40 mL) was added slowly. The mixture was stirred for 15 min and NEt3 (14.3 mL, 103 mmol) was added slowly. After stirring for 15 min the ice bath was removed and the mixture was stirred for additional 16 hr. The mixture was diluted with water (100 mL). The separated organic layer was washed with brine (1×˜75 mL), dried over Na2SO4, filtered off and concentrated in vacuo. The resulting residue was purified by column chromatography [SiO2, 120 g, EtOAc/hexane= 10/90 to 50/50] providing 4-(dibenzylamino)cyclohexanone as a white solid. Yield: 5.5 g. LCMS (m/z): 294.1 [M+H]+; Retention time=0.58 min.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[N:6][CH:7]=1.[C:12]1(C)C=CC=C[C:13]=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C=C>C(#N)C.C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:12]([C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[N:6][CH:7]=1)=[CH2:13]
Reactant: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Reactant: CC(=O)Nc1ccc(Br)cn1
Agent: [Pd+2]
Agent: C=C
Agent: CC(=O)[O-]
Solvent: CC#N
Solvent: CCN(CC)CC
Product: C=Cc1ccc(NC(C)=O)nc1
Temperature: 85 °C
Yield: 1924.4 %

Procedure:
A solution of of N-(5-bromo-pyridin-2-yl)-acetamide (prepared as described in Preparation One, 4.30 g, 20 mmol) in acetonitrile (15 ml) and triethylamine (5.04 ml) was treated with palladium acetate (45 mg, 0.2 mmol) and tri-o-tolylphosphine (203 mg, 0.66 mmol). The mixture was placed in a pressure reactor under 50 psig of ethylene pressure and heated at 85° C. for 66 hours. The reaction mixture was cooled, vented, and partitioned between phosphate buffer (0.1M, pH 6.6) and ethyl acetate. The aqueous phase was extracted with ethyl acetate twice more. The combined ethyl acetate extracts were washed with additional phosphate buffer, brine and dried over sodium sulfate. The extracts were filtered and evaporated to afford 2.06 g (63%) of the title product as a flaky crystalline residue. Recrystallization from ethyl acetate/cyclohexane gave colorless flakes. mp 120-121° C. 1H NMR (CDCl3): δ=8.55 (br, 1H); 8.24 (d, 1H); 8.15 (d, 1H); 7.76 (d of d, 1H); 6.64 (d of d, 1H); 5.73 (d, 1H); 5.28 (d, 1H); 2.19 (s, 3H). MS (CI): m/z=163 (M+H+).
Reaction SMILES: C1CO[C:8]23OCCO[C:3]2([C@:4]2([CH2:27][CH2:26][C@H:25]4[C@@H:15]([CH2:16]/[C:17](=[N:28]\[O:29][CH2:30][CH:31]=[CH2:32])/[CH:18]5[C@:23]4([CH3:24])[CH2:22][CH2:21][CH2:20][CH2:19]5)[C@@H:6]2[CH2:7]3)[CH3:5])[O:2]1.C([C@@H]1C2[C@](C)(CCC(=[O:53])C2)[C@@H]2[C@H]([C@H]3[C@@](CC2)(C)C(=O)CC3)C1)#N>>[CH2:30]([O:29]/[N:28]=[C:17]1\[CH2:16][C@@H:15]2[C@@H:25]([C@:23]3([CH3:24])[CH:18]\1[CH2:19][C:20](=[O:53])[CH2:21][CH2:22]3)[CH2:26][CH2:27][C@@:4]1([CH3:5])[C@H:6]2[CH2:7][CH2:8][C:3]1=[O:2])[CH:31]=[CH2:32]
Reactant: C[C@]12CCC(=O)CC1[C@@H](C#N)C[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Reactant: C=CCO/N=C1\C[C@@H]2[C@H](CC[C@@]3(C)[C@H]2CC24OCCOC23OCCO4)[C@@]2(C)CCCCC12
Product: C=CCO/N=C1\C[C@@H]2[C@H](CC[C@]3(C)C(=O)CC[C@@H]23)[C@@]2(C)CCC(=O)CC12
Yield: 70 %

Procedure:
The title compound II-aw was prepared in 70% yield from 3,3:17,17-bis(ethylendioxy)-6(E)-allyloxyiminoandrostane by the procedure described above for the preparation of 6α-cyanoandrostane-3,17-dione (II-ac, Prepn. 3). The combined organic extracts were washed with H2O, dried over Na2SO4 and evaporated to dryness. 1H-NMR (300 MHz, acetone-d6, ppm from TMS): δ 5.99 (1H, m), 5.25 (1H, m), 5.14 (1H, m), 4.52 (2H, m), 4.42 (1H, dd), 2.68-1.15 (19H, m), 1.01 (3H, s), 0.88 (3H, s).
Reaction SMILES: [CH2:1]1[C:6](=[O:7])[S:5][CH2:4][C:2]1=[O:3].C(N(CC)CC)C.[CH:15]1([CH:27]([CH2:31][CH3:32])C(O)=O)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.CC1C=CC(S([O-])(=O)=O)=CC=1.C[N+]1(CCN=C=NC2CCCCC2)CC[O:48][CH2:47]C1>ClCCl.CN(C)C1C=CN=CC=1>[CH:15]1([CH2:27][CH2:31][CH2:32][C:47]([C:1]2[C:6](=[O:7])[S:5][CH2:4][C:2]=2[OH:3])=[O:48])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]1
Reactant: C[N+]1(CCN=C=NC2CCCCC2)CCOCC1
Reactant: CCC(C(=O)O)C1CCCCCCCCCCC1
Reactant: O=C1CSC(=O)C1
Agent: CN(C)c1ccncc1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(CCCC1CCCCCCCCCCC1)C1=C(O)CSC1=O
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 33.4 %

Procedure:
To a dry flask under N2 atmosphere at 0° C. is added 1.31 g (11.3 mmol) of thiotetronic acid in 40 mL of dry dichloromethane followed by 1.42 mL (10.2 mmol) of triethylamine and 0.38 g (3.1 mmol) of 4-dimethylaminopyridine. After stirring at 0° C. for 5 minutes, 2.6 g (10.2 mmol) of cyclododecylbutanoic acid is added, followed by 4.8 g (11.3 mmol) of 1-cyclohexyl-3-(2-morpholinoethyl) carbodiimide metho p-toluenesulfonate. After stirring for 10 minutes, the reaction mixture is allowed to warm to room temperature and is stirred overnight. The reaction mixture is quenched with 1N HCl. The layers are separated and the aqueous phase is washed once with dichloromethane. The combined organic layers are washed twice with aqueous sodium bicarbonate and twice with aqueous 2N HCl. The organic phase is then dried over MgSO4 and the dichloromethane evaporated. The residue is flash chromatographed on acidic silica gel using 8% ether/hexanes, dissolved in ether, washed with 1N HCl, dried and evaporated to give 1.2 g of a white solid: m.p. 62°-69° C.; IR; NMR (CDCl3) δ 1.2-1.4 (m, 10H), 1.5 (s, 4H), 1.65 (m, 2H), 2.9 (t, 2H, J=7 Hz), 3.96 (s, 2H); MS.