1-ETHYLOXYCARBONYL-5-BOC-3-AMINO-4,6-DIHYDRO-PYRROLO[3,4-C]PYRAZOLE

A solution of ethyl chlorocarbonate (8.9 ml, 93 mmol) in THF (250 ml) was added slowly to a mixture of 3-amino-4, 6-dihydro-lH-pyrrolo [3, 4-C] ole-5-carboxylic acid tert-butyl ester (20 g, 89 mmol) and DIISOPROPYLETHYLAMINE (DIEA, 92 ml, 528 mmol) in THF (500 ml) at 0-5°C. The reaction was kept at the same temperature for two hours then allowed to reach room temperature and stirred overnight. The obtained mixture was evaporated to dryness under vacuum. The resulting residue was extracted with ethyl acetate and water. The organic phase was separated, dried over sodium sulfate and evaporated to dryness. The mixture was purified by flash-chromatography (eluent : ethyl ACETATE/EYCLOHEXANE 4/6 to 7/3) to give 19 g (72percent yield) of the title compound as a white solid. 1H-NMR (400 MHZ, DMSO-S6) ppm: 10. 06 (S, broad signal, 2H), 4. 4-4. 05 (M, 6H), 1.27 (t, 3H) 1 (2, 9H).EXAMPLE 27 To a solution of tert-butyl 3-cyano-4-oxopyrrolidine-1-carboxylate 1 (40.00 g, 0.18 mol) and ethyldiisopropylamine (DIEA) (138.00 g, 1.06 mol) in dry THF (700 mL) was added dropwise a solution of ethyl chlorocarbonate (20.20 g, 0.19 mol) in dry THF (250 mL) over a period of 1 h at 0-5 °C. The reaction mixture was stirred for 12 h at room temperature and concentrated under reduced pressure. The residue was treated with ethyl acetate (500 mL), washed successively with water and saturated saline, dried over anhydrous MgSOSynthesis of compound 9b Ethyl chloroformate (4.5 ml, 46.5 mmol) was dissolved in tetrahydrofuran (100 ml), with ice bath, compound 8b (10 g, 44.5 mmol) and DIPEA (46 ml, 264 mmol) were dissolved in tetrahydrofuran (250 ml), at 0-5 °C add the drops into reaction solution, then rise to the room temperature for reaction of 16 hours, then vacuum evaporate the reaction solution and dissolve the residue with ethyl acetate, and wash the organic phase with water, dry the organic phase with sodium sulfate, vacuum evaporate the solvent with lower pressure, purify the residue with silica gel layer chromatography (ethyl acetate: petroleum ester=1:3), to give the white solid(compound 9b : 8.0 g, 60.7percent yield). Step 1. 5-(tert-butyl) 1-ethyl 3-amino-4, 6-dihydropyrrolo[3, 4-c]pyrazole-1, 5-dicarboxylate(6) 24.8 g (0.11 mol) of the general formula (16) was added to 200 mL of THF, DIEA 18.3 mL (0.11 mol) was added with stirring under ice-salt bath, And 10.5 mL (0.11 mol) of ethyl chloroformate diluted with THF was added dropwise thereto. The temperature was controlled to 0 ° C or lower, Reaction 5-6 h, TLC monitoring. Post-treatment, concentration under reduced pressure, extraction with methylene chloride, Washed with saturated NaCl, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to give the compound of formula (17) as a pale yellow solid, 30.0 g.To a solution of tert-butyl 3-amino-4, 6-dihydropyrrolo[3, 4-c]pyrazole-5(lH)-carboxylate (2.600 g, 11.607 mmol) in THF (30 ml) was added DIPEA (11.8 ml, 69.6 mmol) at 0°C. Ethyl chloroformate (1.11 ml, 11.72 mmol) was added dropwise to the reaction mixture at 0°C. The reaction mixture was stirred at 0°C for 10 min and then at rt for 2 h. The reaction mixture was poured into water (60 ml) and extracted with EtOAc (3 x 60 ml). The combined organic layer was dried over Na5) 33.1 g (0.16 mol) of the general formula (14) was added to 200 mL of anhydrous ethanol, 22.4 g (0.16 mol) of ethyl hydrazinecarboxylate hydrochloride was added in portions, and the reaction was carried out at 60 ° C for 4 to 5 hours. The reaction was monitored by TLC.The filtrate was concentrated under reduced pressure to give 40.3 g of a white solid of general formula (17).

Molecular Weight:296.32
XLogP3:0.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Rotatable Bond Count:4
Exact Mass:296.14845513
Monoisotopic Mass:296.14845513
Topological Polar Surface Area:99.7
Heavy Atom Count:21
Complexity:423
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes