Trifluoroacetic acid → N-[(1R,6R)-6-Amino-2,2-difluorocyclohexyl]-4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophene-2-carboxamide

HRID 1842609노트

반응식

HRID 1842609 반응식
C(OC(=O)[NH:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][C:10]([F:15])([F:14])[C@@H:9]1[NH:16][C:17]([C:19]1[S:20][C:21]([CH3:37])=[C:22]([C:24]2[CH:25]=[N:26][N:27]3[CH:32]=[C:31]([O:33][CH:34]([F:36])[F:35])[CH:30]=[N:29][C:28]=23)[CH:23]=1)=[O:18])(C)(C)C.FC(F)(F)C(O)=O>ClCCl.[OH-].[Na+]>[NH2:7][C@H:8]1[C@@H:9]([NH:16][C:17]([C:19]2[S:20][C:21]([CH3:37])=[C:22]([C:24]3[CH:25]=[N:26][N:27]4[CH:32]=[C:31]([O:33][CH:34]([F:35])[F:36])[CH:30]=[N:29][C:28]=34)[CH:23]=2)=[O:18])[C:10]([F:14])([F:15])[CH2:11][CH2:12][CH2:13]1

참가 물질

5

반응물 2

HCID 6422Trifluoroacetic acidHCID 89750994tert-Butyl{(1R,2R)-2-[({4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophen-2-yl}carbonyl)amino]-3,3-difluorocyclohexyl}carbamate

생성물 1

HCID 86692126N-[(1R,6R)-6-Amino-2,2-difluorocyclohexyl]-4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophene-2-carboxamide수율 50.4%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 14798Sodium Hydroxide용매

실험 절차

tert-Butyl{(1R,2R)-2-[({4-[6-(difluoromethoxy)pyrazolo[1,5-a]pyrimidin-3-yl]-5-methylthiophen-2-yl}carbonyl)amino]-3,3-difluorocyclohexyl}carbamate (0.900 g, 1.61 mmol) was dissolved in dichloromethane (8 mL) and trifluoroacetic acid (1.50 mL, 19.5 mmol) added. The reaction was stirred at room temperature for 16 h. After deprotection was complete, the mixture was diluted with 1N NaOH. The aqueous layer was extracted 3× with dichloromethane. The organic layers were combined, dried with sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (0-16% MeOH/DCM) to give the title compound (0.371 g, 0.811 mmol). LRMS (APCI) calc'd for (C19H19F4N5O2S) [M+H]+, 458.1; found 458.0. 1H NMR (CDCl3, 500 MHz) δ 8.66 (d, J=2.5, 1H), 8.48 (d, J=2.5, 1H), 8.26 (s, 1H), 7.92 (s, 1H), 7.06 (d, J=8.8, 1H), 6.61 (t, J=71.5, 1H), 4.45 (m, 1H), 3.32 (m, 1H), 2.57 (s, 3H), 2.17 (m, J=8.6, 1H), 1.47-1.92 (m, 5H).

후처리

  1. extractionThe aqueous layer was extracted 3× with dichloromethane
  2. dry with materialdried with sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by column chromatography (0-16% MeOH/DCM)

출처 및 근거

ORD 기록
ord-fc013c79a300418a9e14d410be896551
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946237B2

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