Sodium hydride → tert-butyl 4-(5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

HRID 387556

반응식

HRID 387556 반응식
[H-].[Na+].[Br:3][C:4]1[CH:9]=[N:8][C:7]2[N:10]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[N:11]=[CH:12][C:6]=2[C:5]=1O.FC(F)(F)S(N(C1C=CC=CC=1)S(C(F)(F)F)(=O)=O)(=O)=O.[N:44]1([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1.[Cl-].[NH4+]>CN(C)C=O>[Br:3][C:4]1[C:5]([N:47]2[CH2:46][CH2:45][N:44]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:49][CH2:48]2)=[C:6]2[CH:12]=[N:11][N:10]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[C:7]2=[N:8][CH:9]=1

참가 물질

7

반응물 5

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 142176Phenyl triflimideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 178490902HCID 178490902, 화합물

생성물 1

HCID 68760849tert-butyl 4-(5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate수율 82%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

반응 조건

온도
40 °C

실험 절차

NaH (0.144 g, 3.59 mmol) in DMF (5 mL) was added dropwise to a solution of 5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-ol (1.00 g, 2.99 mmol) in dimethylformamide (“DMF”) (10 mL). The reaction mixture was warmed to 40° C. and stirred for 30 minutes. After cooling to room temperature, 1,1,1-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (1.28 g, 3.59 mmol) was added and stirred at room temperature for 1 hour. tert-Butyl piperazine-1-carboxylate (1.23 g, 6.58 mmol) was then added. The mixture was warmed to 80° C. and stirred for 1 hour. The reaction was then cooled to room temperature, and a saturated ammonium chloride solution (30 mL) was added. The reaction mixture was extracted with ethyl acetate (2×20 mL) and dried over sodium sulfate, filtered and concentrated. The resulting residue was purified by column chromatography (hexane:ethyl acetate, 5:1) to give tert-butyl 4-(5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (1.23 g, 82%) as a solid. MS ESI (+) m/z 504.3 detected. 1H NMR (400 Hz, DMSO-d6) δ 8.42 (s, 1H), 8.28 (s, 1H), 7.17 (d, J=8.8 Hz, 2H), 6.82 (d, J=8.8 Hz, 2H), 5.48 (s, 2H), 3.66 (s, 3H), 3.49 (m, 8H), 1.40 (s, 9H).

후처리

  1. temperatureAfter cooling to room temperature
  2. stirringstirred at room temperature for 1 hour
  3. temperatureThe mixture was warmed to 80° C.
  4. stirringstirred for 1 hour
  5. temperatureThe reaction was then cooled to room temperature
  6. extractionThe reaction mixture was extracted with ethyl acetate (2×20 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by column chromatography (hexane:ethyl acetate, 5:1)

출처 및 근거

ORD 기록
ord-109c929bb6d34a279b1dba6de1a8e077
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08372842B2

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