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Water → 4-[4-(2,4,5-Trifluoro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1931643
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HRID 1931643 반응식
C(=O)([O-])[O-].[K+].[K+].[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH:17]([N:20]2[C:24]3=[N:25][CH:26]=[N:27][C:28](Cl)=[C:23]3[CH:22]=[N:21]2)[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].[F:30][C:31]1[CH:36]=[C:35]([F:37])[C:34]([F:38])=[CH:33][C:32]=1[OH:39].O>CN(C)C=O.C(OCC)C>[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH:17]([N:20]2[C:24]3=[N:25][CH:26]=[N:27][C:28]([O:39][C:32]4[CH:33]=[C:34]([F:38])[C:35]([F:37])=[CH:36][C:31]=4[F:30])=[C:23]3[CH:22]=[N:21]2)[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]
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참가 물질

7

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 1231532,4,5-TrifluorophenolHCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2회

생성물 1

HCID 579648894-[4-(2,4,5-Trifluoro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester수율 50%

시약·촉매·용매

2
HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매

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온도
100 °C

실험 절차

Potassium carbonate (53 mg, 0.39 mmol) was added to a solution of 4-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 19; 100 mg, 0.3 mmol) and 2,4,5-trifluoro-phenol (available from Alfa Aesar, Ward Hill, Mass., USA; 57 mg, 0.39 mmol) in dimethylformamide (5 mL). The reaction mixture was heated at 100° C. in an oil bath overnight, then it was cooled to room temperature, and water and diethyl ether were added. The aqueous phase was extracted twice with diethyl ether and three times with hexane. The combined organic phases were evaporated and the resulting residue was purified by C18 reversed phase HPLC using a gradient of 20-100% acetonitrile/water to give 4-[4-(2,4,5-trifluoro-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (66 mg, 50%) as a white powder. 1H NMR (300 MHz, CDCl3) δ 1.49 (s, 9H), 1.95-2.06 (m, 2H), 2.18-2.34 (m, 2H), 2.90-3.06 (m, 2H), 4.26-4.38 (m, 2H), 4.90-5.02 (m, 1H), 7.09-7.21 (m, 2H), 8.16 (s, 1H), 8.49 (s, 1H). HRMS Calcd. for C21H23F3N5O3 (MH+): 450.1748. Found: 450.1745.

후처리

  1. temperatureit was cooled to room temperature
  2. extractionThe aqueous phase was extracted twice with diethyl ether and three times with hexane
  3. customThe combined organic phases were evaporated
  4. customthe resulting residue was purified by C18 reversed phase HPLC

출처 및 근거

ORD 기록
ord-64032aa69c4a4c91a9a1f3c64b5fd771
출처 데이터셋
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08188098B2

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