4-(Trifluoromethyl)benzoyl chloride → N1-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-4-(trifluoromethoxy)benzamide

HRID 897963

Reaktionsgleichung

Reaktionsgleichung von HRID 897963
[F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](Cl)=[O:11])=[CH:6][CH:5]=1.[NH2:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2[C:30]3[C:25](=[N:26][CH:27]=[N:28][C:29]=3[NH2:31])[N:24]([CH:32]3[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]3)[N:23]=2)=[CH:18][C:17]=1[O:39][CH3:40].FC(F)(F)C1C=CC(C(Cl)=O)=CC=1>ClCCl.N1C=CC=CC=1>[NH2:31][C:29]1[N:28]=[CH:27][N:26]=[C:25]2[N:24]([CH:32]3[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]3)[N:23]=[C:22]([C:19]3[CH:20]=[CH:21][C:16]([NH:15][C:10](=[O:11])[C:7]4[CH:8]=[CH:9][C:4]([O:3][C:2]([F:14])([F:13])[F:1])=[CH:5][CH:6]=4)=[C:17]([O:39][CH3:40])[CH:18]=3)[C:30]=12

Komponenten

6

Edukt 3

HCID 676074-(Trifluoromethyl)benzoyl chlorideHCID 1421104-(Trifluoromethoxy)benzoyl ChlorideHCID 223470163-(4-amino-3-methoxyphenyl)-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Produkt 1

HCID 22346799N1-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-4-(trifluoromethoxy)benzamideAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1049PyridineLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

4-(Trifluoromethoxy)-1-benzenecarbonyl chloride (38 mg, 0.170 mmol) in dichloromethane (0.3 mL) was added to a solution of 3-(4-amino-3-methoxyphenyl)-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (60 mg, 0.17 mmol) in pyridine (1.2 mL) at 0° C. After 5 minutes, the ice-water bath was removed and the reaction mixture was stirred at room temperature for 1 hours then, more 4-(trifluoromethyl)-1-benzenecarbonyl chloride (19 mg, 0.085 mmol) was added. After 2 hours, the solvent was evaporated and the residue was purified by flash column chromatography using dichloromethane/methanol (95:5 to 70:30) as mobile phase to give N1-{4-[4-amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-4-(trifluoromethoxy)benzamide (70 mg, 76%). 1H NMR (CDCl3) δ 2.06 (d, J=11.79 Hz, 2H), 2.28 (m, 2H), 2.40 (s, 3H), 2.50 (m, 2H), 3.07 (d, J=10.8 Hz, 2H), 4.02 (s, 3H), 4.80 (m, 1H), 5.71 (s, 2H), 7.27 (m, 2H), 7.36 (d, J=8.20 Hz, 2H), 7.98 (d, J=6.20 Hz, 2H), 8.37 (s, 1H), 8.59 (s, 1), 8.67 (d, J=8.55 Hz, 1H). LCMS (Thermoquest AQA single Quad MS, Finnigan HPLC-Column: Genesis, C18, 3 um, 33×4.6 mm. Eluents: 30% B/A to 95% B/A in 4.5 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 0.8 mL/min.): MH+=542.3, Rt=1.98 min.

Aufarbeitung

  1. customthe ice-water bath was removed
  2. waitAfter 2 hours
  3. customthe solvent was evaporated
  4. customthe residue was purified by flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-93396f3371a44241ae8ab64e627dbc7e
Quelldatensatz
uspto-grants-2005_07
Patentnummer
US06921763B2

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