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 1854933Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1854933
[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

Komponenten

5

Edukt 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

Produkt 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-cyclopropylacrylonitrileAusbeute 17 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

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 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]+, 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).

Aufarbeitung

  1. customInto a 10 mL sealed tube
  2. concentrationconcentrated under vacuum
  3. additionThe residue was diluted with 10 mL 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)

Quellen und Nachweise

ORD-Eintrag
ord-6bb55a4a78504ab9a630e7e4749e2864
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08962831B2

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