Diisopropylethylamine → (1,5-dimethyl-1H-pyrazol-3-yl)-{4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidin-1-yl}-methanone

HRID 1931755

반응식

HRID 1931755 반응식
FC(F)(F)C(O)=O.[CH3:8][S:9]([C:12]1[CH:33]=[CH:32][C:15]([O:16][C:17]2[N:22]=[CH:21][N:20]=[C:19]3[N:23]([CH:26]4[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]4)[N:24]=[CH:25][C:18]=23)=[CH:14][CH:13]=1)(=[O:11])=[O:10].[B-](F)(F)(F)F.CN(C(ON1C(=O)CCC1=O)=[N+](C)C)C.C(N(C(C)C)CC)(C)C.[CH3:63][N:64]1[C:68]([CH3:69])=[CH:67][C:66]([C:70](Cl)=[O:71])=[N:65]1>ClCCl>[CH3:63][N:64]1[C:68]([CH3:69])=[CH:67][C:66]([C:70]([N:29]2[CH2:28][CH2:27][CH:26]([N:23]3[C:19]4=[N:20][CH:21]=[N:22][C:17]([O:16][C:15]5[CH:14]=[CH:13][C:12]([S:9]([CH3:8])(=[O:11])=[O:10])=[CH:33][CH:32]=5)=[C:18]4[CH:25]=[N:24]3)[CH2:31][CH2:30]2)=[O:71])=[N:65]1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 27763641,5-Dimethyl-1H-Pyrazole-3-Carbonyl ChlorideHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 669153264-(4-methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt2회

생성물 1

HCID 57964929(1,5-dimethyl-1H-pyrazol-3-yl)-{4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidin-1-yl}-methanone수율 43.5%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

A mixture of 4-(4-methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 27; 63 mg, 0.13 mmol), TSTU (O—(N-succinimidyl)-1,1,3,3-tetramethyluronium tetrafluoroborate; 78 mg, 0.26 mmol), and diisopropylethylamine (0.14 mL, 0.8 mmol) in dichloromethane (4 mL) was shaken at room temperature for 3 h. 1,5-Dimethyl-1H-pyrazole-3-carbonyl chloride (available from Maybridge, Tintagel, Cornwall, UK; 23 mg, 0.16 mmol) was added and the mixture was shaken at room temperature overnight. The solution was diluted with dichloromethane (˜6 mL) and washed with water (2×5 mL), 1 M aqueous hydrochloric acid (5 mL), water (5 mL), saturated aqueous sodium bicarbonate (5 mL) and brine (5 mL). The organic layer was evaporated and the crude product was purified by HPLC to give (1,5-dimethyl-1H-pyrazol-3-yl)-{4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidin-1-yl}-methanone (28 mg, 43%) as a white solid. Mass spectrum (ES) MH+=496.

후처리

  1. stirringthe mixture was shaken at room temperature overnight
  2. washwashed with water (2×5 mL), 1 M aqueous hydrochloric acid (5 mL), water (5 mL), saturated aqueous sodium bicarbonate (5 mL) and brine (5 mL)
  3. customThe organic layer was evaporated
  4. customthe crude product was purified by HPLC

출처 및 근거

ORD 기록
ord-8f1b826f24484766a25fdc4e3483ccca
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188098B2

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