1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-cyclopentyl-3-(4-(7-(4-(1-methylpiperidin-4-yl)phenyl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile

HRID 1853040Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1853040
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]3[N:19]=[C:18]([C:20]4[CH:21]=[N:22][NH:23][CH:24]=4)[N:17]4[CH:25]=[CH:26][N:27]=[C:16]4[CH:15]=3)=[CH:10][CH:9]=2)[CH2:4][CH2:3]1.[CH:28]1([CH:33]=[CH:34][C:35]#[N:36])[CH2:32][CH2:31][CH2:30][CH2:29]1.N1CCCN2CCCCCC=12>CN(C=O)C>[CH:28]1([CH:33]([N:23]2[CH:24]=[C:20]([C:18]3[N:17]4[CH:25]=[CH:26][N:27]=[C:16]4[CH:15]=[C:14]([C:11]4[CH:12]=[CH:13][C:8]([CH:5]5[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]5)=[CH:9][CH:10]=4)[N:19]=3)[CH:21]=[N:22]2)[CH2:34][C:35]#[N:36])[CH2:32][CH2:31][CH2:30][CH2:29]1

Komponenten

5

Edukt 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 534011163-Cyclopentylprop-2-enenitrile2×HCID 674561367-(4-(1-methylpiperidin-4-yl)phenyl)-5-(1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine

Produkt 1

HCID 674556573-cyclopentyl-3-(4-(7-(4-(1-methylpiperidin-4-yl)phenyl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrileAusbeute 55,19 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

7-(4-(1-Methylpiperidin-4-yl)phenyl)-5-(1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidine (0.130 g, 0.363 mmol) and 3-cyclopentylacrylonitrile (Table 1, compound g; 0.220 g, 1.81 mmol) were suspended in DMF (10 mL) and 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine (0.2169 mL, 1.451 mmol) added in one portion. The reaction mixture was stirred at ambient temperature for 66 hours. The reaction mixture was partitioned between saturated aqueous 1 N NaOH and EtOAc. The organics were washed with brine, dried over MgSO4 and concentrated under reduced pressure to afford the crude material, which was purified by flash column chromatography (eluant: 2-6% (9:1, MeOH:NH4OH)/DCM) to furnish 3-cyclopentyl-3-(4-(7-(4-(1-methylpiperidin-4-yl)phenyl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile (0.096 g, 0.200 mmol, 55.19% yield). MS (apci) m/z=480.3 (M+H).

Aufarbeitung

  1. customThe reaction mixture was partitioned between saturated aqueous 1 N NaOH and EtOAc
  2. washThe organics were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customto afford the crude material, which
  6. customwas purified by flash column chromatography (eluant: 2-6% (9:1, MeOH:NH4OH)/DCM)

Quellen und Nachweise

ORD-Eintrag
ord-b1c9477b76254143b17d951226c4209c
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08962596B2

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