Trifluoroacetic acid → 1-(benzo[d]oxazol-2-yl)-N-(4-(3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)cyclopropanecarboxamide

HRID 2241360노트

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HRID 2241360 반응식
COC1C=CC(C[N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]5([C:30]6[O:31][C:32]7[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=7[N:34]=6)[CH2:29][CH2:28]5)=[O:26])=[CH:20][C:19]=4[F:39])=[C:11]3[C:10]([N:40]3[CH2:45][CH2:44][CH:43]([N:46]([CH3:48])[CH3:47])[CH2:42][CH2:41]3)=[N:9]2)=CC=1.C(O)(C(F)(F)F)=O>>[O:31]1[C:32]2[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=2[N:34]=[C:30]1[C:27]1([C:25]([NH:24][C:21]2[CH:22]=[CH:23][C:18]([O:17][C:16]3[CH:15]=[CH:14][N:13]=[C:12]4[NH:8][N:9]=[C:10]([N:40]5[CH2:41][CH2:42][CH:43]([N:46]([CH3:47])[CH3:48])[CH2:44][CH2:45]5)[C:11]=34)=[C:19]([F:39])[CH:20]=2)=[O:26])[CH2:28][CH2:29]1

참가 물질

3

반응물 2

HCID 6422Trifluoroacetic acidHCID 685161541-(benzo[d]oxazol-2-yl)-N-(4-(3-(4-(dimethylamino)piperidin-1-yl)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)cyclopropanecarboxamide

생성물 1

HCID 593043211-(benzo[d]oxazol-2-yl)-N-(4-(3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)cyclopropanecarboxamide수율 50%

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온도
50 °C

실험 절차

To a flask containing N-(4-(1-(4-methoxybenzyl)-3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-1-(benzo[d]oxazol-2-yl)cyclopropanecarboxamide (6.6 mg, 0.01 mmol) at room temperature under a drying tube was added TFA (2 mL). The reaction was warmed to 50° C. overnight. The reaction was cooled to room temperature and was concentrated. The residue was dissolved in 10 mL dichloromethane and stirred rapidly with 10 mL 10% sodium carbonate solution. The layers were separated and the organics dried (MgSO4). The crude product was concentrated and the crude material was loaded onto a Biotage 12S column with dichloromethane. The column was eluted with a step gradient of dichloromethane (150 mL) and 94.5/5/0.5 dichloromethane/MeOH, concentrated ammonium hydroxide to provide the desires product as a yellow glass (2.7 mg, 50% yield). 1H NMR (400 MHz, CDCl3) δ 12.17 (br s, 1H), 9.92 (br s, 1H), 8.24 (d, 1H), 7.90 (m, 1H), 7.73 (m, 1H), 7.48 (m, 2H), 7.38 (m, 2H), 7.30 (m, 1H), 6.21 (d, 1H), 4.11 (m, 2H), 2.91 (m, 2H), 2.40 (m, 1H), 2.34 (s, 6H), 2.08 (m, 2H), 1.96 (br m, 2H), 1.90 (m, 2H), 1.74 (br m, 2H). LCMS (APCI+): m/z 556 (M+1) detected.

후처리

  1. temperatureThe reaction was cooled to room temperature
  2. concentrationwas concentrated
  3. dissolutionThe residue was dissolved in 10 mL dichloromethane
  4. customThe layers were separated
  5. dry with materialthe organics dried (MgSO4)
  6. concentrationThe crude product was concentrated
  7. washThe column was eluted with a step gradient of dichloromethane (150 mL) and 94.5/5/0.5 dichloromethane/MeOH, concentrated ammonium hydroxide

출처 및 근거

ORD 기록
ord-430fb36ede244a7d9710106c5802ea80
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07723330B2

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