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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
ノート
印刷プレビュー

反応式

HRID 1931643 の反応式
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]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 1231532,4,5-TrifluorophenolHCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2 回

生成物 1

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

試薬・触媒・溶媒

2
HCID 3283Diethyl Ether溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-64032aa69c4a4c91a9a1f3c64b5fd771
出典データセット
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08188098B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート