6-Oxo-2-azaspiro[3.3]heptane-2-carboxy...

Butyl-5, 5-dichloro-6-oxo-2-azaspiro [3.3] heptane-2-carboxylic acid tert-butyl ester (1.65 g, 5.89 mmol, 1.0 eq)Zinc powder (0.85 g, 15.0 mmol, 2.6 eq)Ammonium chloride (1.2 g, 22.0 mmol, 3.8 eq) was added to methanol (30 mL) and reacted at room temperature for 18 h under nitrogen. After completion of the reaction, water (40 mL) was added, EA (30 mL x 2) was extracted, dried, , PE: EA (v / v) = 5: 1 column chromatography to give 0.8 g of product as a white solid in 66.0percent yield.Step 3: Preparation tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate [0219] A solution of tert-butyl 5, 5-dichloro-6-oxo-2-azaspiro[3.3]heptane-2- carboxylate (1 g, 3.5 mmol) in dioxane (20 mL) was added drop wise to a suspension of zinc powder (0.7 g, 10.71 mmol) in acetic acid (20 mL) at 0 °C and the reaction mixture was stirred at room temperature for 15 h. Then the reaction mixture was filtered through celite, filtrate was basified with 33percent sodium hydroxide solution and extracted with ethyl acetate (50 mL x 2). The combined organic extract was washed with brine (50 mL), dried over anhydrous sodium sulfate and evaporated. The crude material was purified by combiflash purifier using 30percent ethyl acetate in hexane to afford the title compound tert-butyl 6-oxo-2- azaspiro[3.3]heptane-2-carboxylate (0.42 g, 58 percent yield) as a pale yellow solid. 1H NMR (400 MHz, CDC1Under nitrogen, 9-[(3aR, 4R, 6R, 6aR)-2, 2-dimethyl-6-[[(propan-2-yl)amino]methyl]-tetrahydro-2H-furo[3, 4- d][1, 3]dioxol-4-yl]-9H-indole-6-amine (I-6, 4.12 g, 11.8 mmol), 6-oxo-2-azaspiro[3.3] tert-butyl heptane-2-carboxylate(IX-3, 2.50g, 11.8mmol)Titanium tetraisopropoxideThe mixture (50 mL) was stirred at 25 C for 16 hours.It was then diluted with methanol (45 mL).Cool to 0 C, Add to the above solution in batchesSodium borohydride (4.50 g, 118 mmol), The resulting reaction solution was stirred at room temperature for 30 minutes.Carefully add 0.1N aqueous sodium hydroxide solution (50 mL) and filter.The filtrate was extracted with ethyl acetate (100 mL×3).Combine the organic phase, Dry with sodium sulfate and filter.The filtrate was concentrated in vacuo.The residue was purified by silica gel column chromatography (eluent:0-10% methanol in ethyl acetate) gave 1.61 g (yield: 25%) of 6-([[(3aR, 4R, 6R, 6aR)-6-(6-amino-9H-indole-9-) -2, 2-dimethyl-tetrahydro-2H-furo[3, 4-d][1, 3]dioxol-4-yl]methyl](propan-2-yl) Amino)-2-azaspiro[3.3]heptane-2-carboxylic acid tert-butyl ester (IX-4), It is a white solid.To a stirred solution of To a solution of 1 (10 g, 0.048mol) in MeOH (100 mL) was added methylamine alcohol solution (9.8 g, 0.095 mol) at 25 °C. The reaction mixture was stirred at the same temperature for 15 hrs, then NaBLE (3.6 g, 0.095 mol) was added in small portions, the mixture was stirred at 25 °C for 2 hours, at that moment TLC monitored the reaction showed that it had gone to completely. So it was poured into ammonium chloride aqueous (100 mL), then it was concentrated, then extracted with EtOAc (3 x 100 mL), the combined organic phases were washed with saturates brine, the organic layers was concentrated under reduced pressure, the residue was purified by column chromatography to give 2 (9.5 g, yield: 88percent) as an colourless oil. MS: m/z [M+H]+ 227.3.

Molecular Weight:211.26
XLogP3:0.5
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:211.12084340
Monoisotopic Mass:211.12084340
Topological Polar Surface Area:46.6
Heavy Atom Count:15
Complexity:300
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes