Hydrazine → tert-butyl 8-(2,2-difluoroethyl)-10-(4-methyl-1H-pyrazol-5-yl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

tert-Butyl 8-(2,2-difluoroethyl)-10-propanoyl-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (225 mg, 0.598 mmol) and DMF-DMA (1.0 mL, 7.53 mmol) were heated in a sealed vial at 105° C. overnight. The reaction mixture was concentrated and then diluted with methanol (1 mL). Hydrazine (60 μL, 1.9 mmol) was added in 3 aliquots every hour over 3 hours and then the reaction mixture was stirred for an additional 1 hour. The reaction mixture was diluted with methanol, microfiltered and purified by preparative LCMS (10-99% ACN/Water, HCl modifier) to give tert-butyl 8-(2,2-difluoroethyl)-10-(4-methyl-1H-pyrazol-5-yl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (80 mg, 0.2 mmol, 33.42%) as a yellow oil. ESI-MS m/z calc. 400.2. found 401.5 (M+1)+; Retention time: 1.36 minutes (3 min run).

1. concentrationThe reaction mixture was concentrated
2. additiondiluted with methanol (1 mL)
3. custommicrofiltered and purified by preparative LCMS (10-99% ACN/Water, HCl modifier)

ORD 기록

ord-3529d86c7efd47109734e8419a357d54

출처 데이터셋

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09181273B2