Cesium carbonate → 5-{3-[1-(4-Amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-6-cyano-2-methoxyphenyl}-N,N-dimethylpyridine-2-carboxamide

HRID 1499899Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1499899
C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:7][C:8]1[C:16]2[C:11](=[N:12][CH:13]=[N:14][C:15]=2[NH2:17])[NH:10][N:9]=1.[Cl:18][C:19]1[C:20]([C:41]#[N:42])=[C:21]([C:30]2[CH:31]=[CH:32][C:33]([C:36]([N:38]([CH3:40])[CH3:39])=[O:37])=[N:34][CH:35]=2)[C:22]([O:28][CH3:29])=[C:23]([CH:25](Cl)[CH3:26])[CH:24]=1>CN(C)C=O.CCOC(C)=O>[NH2:17][C:15]1[N:14]=[CH:13][N:12]=[C:11]2[N:10]([CH:25]([C:23]3[C:22]([O:28][CH3:29])=[C:21]([C:30]4[CH:31]=[CH:32][C:33]([C:36]([N:38]([CH3:39])[CH3:40])=[O:37])=[N:34][CH:35]=4)[C:20]([C:41]#[N:42])=[C:19]([Cl:18])[CH:24]=3)[CH3:26])[N:9]=[C:8]([CH3:7])[C:16]=12

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 866778215-[3-chloro-5-(1-chloroethyl)-2-cyano-6-methoxyphenyl]-N,N-dimethylpyridine-2-carboxamideHCID 178434474HCID 178434474, Verbindung

Produkt 1

HCID 866778225-{3-[1-(4-Amino-3-methyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl]-5-chloro-6-cyano-2-methoxyphenyl}-N,N-dimethylpyridine-2-carboxamideAusbeute 84,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Cesium carbonate (3000 mg, 10 mmol) was added to a mixture of 3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (1100 mg, 7.1 mmol) and 5-[3-chloro-5-(1-chloroethyl)-2-cyano-6-methoxyphenyl]-N,N-dimethylpyridine-2-carboxamide (1.8 g, 4.8 mmol) in N,N-dimethylformamide (50 mL). The reaction was stirred at 80° C. for 3 hrs and was allowed to cool to room temperature. The reaction was diluted with EtOAc, washed with water, brine, dried over Na2SO4, filtered and concentrated to give the crude product. This was purified by FCC on silica gel eluting (hexanes/10% EtOH in EtOAc, 0-100%) gradient to give the title compound as light yellow oil (2.0 g, 80%). LCMS calculated for C24H24ClN8O2 (M+H)+: m/z=491.1; found: 491.2. NMR (400 MHz, CD3OD) δ 8.74 (d, J=1.4 Hz, 1H), 8.15 (d, J=2.2 Hz, 1H), 8.13 (s, 1H), 7.77 (d, J=8.1 Hz, 1H), 7.74 (s, 1H), 6.43 (q, J=7.0 Hz, 1H), 3.32 (s, 3H), 3.16 (s, 3H), 3.07 (s, 3H), 2.64 (s, 3H), 1.89 (d, J=7.1 Hz, 3H).

Aufarbeitung

  1. temperatureto cool to room temperature
  2. washwashed with water, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude product
  7. customThis was purified by FCC on silica gel eluting (hexanes/10% EtOH in EtOAc, 0-100%) gradient

Quellen und Nachweise

ORD-Eintrag
ord-6b0b39951278498e94a402c05b61c23c
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09199982B2

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