Piperidine → (R)-2-(3-(4-amino-3-(4-(2,3-difluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-3-cyclopropylacrylonitrile

HRID 1850987노트

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HRID 1850987 반응식
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:26]3[CH2:31][CH2:30][CH2:29][N:28]([C:32](=[O:36])[CH2:33][C:34]#[N:35])[CH2:27]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:19]=4[F:25])=[CH:13][CH:12]=3)[C:3]=12.[CH:37]1([CH:40]=O)[CH2:39][CH2:38]1.N1CCCCC1>CO>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:26]3[CH2:31][CH2:30][CH2:29][N:28]([C:32]([C:33](=[CH:40][CH:37]4[CH2:39][CH2:38]4)[C:34]#[N:35])=[O:36])[CH2:27]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:19]=4[F:25])=[CH:13][CH:12]=3)[C:3]=12

참가 물질

5

반응물 3

HCID 8082PiperidineHCID 123114CyclopropanecarboxaldehydeHCID 867144883-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-oxopropanenitrile

생성물 1

HCID 86714489(R)-2-(3-(4-amino-3-(4-(2,3-difluorophenoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-3-cyclopropylacrylonitrile수율 17%

시약·촉매·용매 1

HCID 887Methanol용매

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온도
25 °C

실험 절차

Into a 10 mL sealed tube, was placed a solution of 3-[(3R)-3-[4-amino-3-[4-(2,3-difluorophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-oxopropanenitrile (150 mg, 0.31 mmol, 1.00 equiv) in methanol (5 mL), cyclopropanecarbaldehyde (64 mg, 0.91 mmol, 3.0 equiv), and piperidine (78 mg). The resulting solution was stirred for 12 h at 25° C. and then concentrated under vacuum. The residue was diluted with 10 mL of dichloromethane and the resulting mixture was washed with saturated aqueous ammonium chloride, water and brine and dried over anhydrous sodium sulfate and concentrated. The residue was loaded onto a silica gel column and elution with dichloromethane/methanol (20/1) gave 28.5 mg (17%) of the title compound as a white solid. LC-MS: (ES, m/z): 542 [M+H]1, H-NMR (300 MHz, CDCl3, ppm): δ 8.54 (s, 1H); δ7.68 (d, 2H); δ7.20 (d, 2H); δ7.16 (d, 2H); δ6.95 (m, 1H); δ6.55 (d, 1H); δ5.52 (s, 2H); δ6.98 (m, 1H); δ4.76 (m, 1H); δ4.34 (m, 1H); δ3.82 (m, 1H); δ3.23 (m, 1H); δ2.01˜δ2.42 (m, 4H); δ1.88 (m, 1H); δ0.85˜δ1.21 (m, 4H).

후처리

  1. customInto a 10 mL sealed tube
  2. concentrationconcentrated under vacuum
  3. additionThe residue was diluted with 10 mL of dichloromethane
  4. washthe resulting mixture was washed with saturated aqueous ammonium chloride, water and brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. washThe residue was loaded onto a silica gel column and elution with dichloromethane/methanol (20/1)

출처 및 근거

ORD 기록
ord-622f489c8d3e4cb19c4173dcbaa8ca2e
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08957080B2

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