Sodium hydride → 4-[4-(4-Methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1931666노트

반응식

HRID 1931666 반응식
[H-].[Na+].[CH3:3][S:4]([C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)(=[O:6])=[O:5].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][CH:24]([N:27]2[C:31]3=[N:32][CH:33]=[N:34][C:35](Cl)=[C:30]3[CH:29]=[N:28]2)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15].[Cl-].[NH4+]>CN(C)C=O>[C:14]([O:18][C:19]([N:21]1[CH2:22][CH2:23][CH:24]([N:27]2[C:31]3=[N:32][CH:33]=[N:34][C:35]([O:13][C:10]4[CH:11]=[CH:12][C:7]([S:4]([CH3:3])(=[O:5])=[O:6])=[CH:8][CH:9]=4)=[C:30]3[CH:29]=[N:28]2)[CH2:25][CH2:26]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

참가 물질

6

반응물 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 1233504-(Methylsulfonyl)phenolHCID 57964905Tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-D]pyrimidin-1-YL)piperidine-1-carboxylate2회

생성물 1

HCID 532576834-[4-(4-Methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester수율 52.8%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

Sodium hydride (60% dispersion in mineral oil; 82 mg, 2.1 mmol) was added to a solution of 4-(methylsulfonyl)phenol (281 mg, 1.6 mmol) in dimethylformamide (9 mL) and the mixture was stirred at room temperature for 20 min. A solution of 4-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylic acid tert-butyl ester (Intermediate 19; 551 mg, 1.6 mmol) in dimethylformamide (5 mL) was added, and the reaction mixture was stirred at room temperature for 3.5 h. Saturated aqueous ammonium chloride solution was added and the mixture was extracted with ethyl acetate (3×90 mL). The organic layer was washed with water (3 times) and brine, dried (sodium sulfate), filtered, evaporated and purified on a flash silica column (40 mm×4″) eluting with 66-75% ethyl acetate/hexanes to give 4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (400 mg, 52%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 1.41 (s, 9H), 1.92-2.02 (m, 4H), 2.94-3.05 (m, 2H), 3.28-3.30 (m, methyl sulfone and water peak), 4.04-4.12 (m, 2H), 4.94-5.06 (m, 1H), 7.59-7.64 (m, 2H), 8.01-8.06 (m, 2H), 8.37 (s, 1H), 8.54 (s, 1H). Mass spectrum (ES) MH+=474.

후처리

  1. stirringthe reaction mixture was stirred at room temperature for 3.5 h
  2. extractionthe mixture was extracted with ethyl acetate (3×90 mL)
  3. washThe organic layer was washed with water (3 times) and brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified on a flash silica column (40 mm×4″)
  8. washeluting with 66-75% ethyl acetate/hexanes

출처 및 근거

ORD 기록
ord-740e5c5c830e4288903738142fcb1776
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188098B2

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