trans-2-Phenyl-1-cyclopropanecarbonyl chloride → N1-{4-[4-Amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-trans-2-phenyl-1-cyclopropanecarboxamide

HRID 897961

Reaktionsgleichung

Reaktionsgleichung von HRID 897961
[C:1]1([C@@H:7]2[CH2:9][C@H:8]2[C:10](Cl)=[O:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:28]3[C:23](=[N:24][CH:25]=[N:26][C:27]=3[NH2:29])[N:22]([CH:30]3[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]3)[N:21]=2)=[CH:16][C:15]=1[O:37][CH3:38]>ClCCl.N1C=CC=CC=1>[NH2:29][C:27]1[N:26]=[CH:25][N:24]=[C:23]2[N:22]([CH:30]3[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]3)[N:21]=[C:20]([C:17]3[CH:18]=[CH:19][C:14]([NH:13][C:10]([C@@H:8]4[CH2:9][C@H:7]4[C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)=[O:11])=[C:15]([O:37][CH3:38])[CH:16]=3)[C:28]=12

Komponenten

5

Edukt 2

HCID 13656trans-2-Phenyl-1-cyclopropanecarbonyl chloride2×HCID 223470163-(4-amino-3-methoxyphenyl)-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Produkt 1

HCID 20817143N1-{4-[4-Amino-1-(1-methyl-4-piperidyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-trans-2-phenyl-1-cyclopropanecarboxamideAusbeute 89 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1049PyridineLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

trans-2-Phenyl-1-cyclopropanecarbonyl chloride (31 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 trans-2-Phenyl-1-cyclopropanecarbonyl chloride (15 mg, 0.083 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}-trans-2-phenyl-1-cyclopropanecarboxamide (75 mg, 89%). 1H NMR (CDCl3) δ 1.42 (m, 1H), 1.77 (m, 1H), 1.85 (m, 1H), 2.03 (m, 1H), 2.24 (m, 2H), 2.37 (s, 3H), 2.46 (m, 2H), 2.62 (m, 1H), 3.05 (m, 2H), 3.96 (s, 3H), 4.77 (m, 1H), 5.69 (s, 2H), 7.24 (m, 7H), 8.11 (s, 1H), 8.35 (m, 1H), 8.45 (d, J=8.38 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+=498.3, Rt=1.84 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-02bf7232514b4806ab66987232a69a8e
Quelldatensatz
uspto-grants-2005_07
Patentnummer
US06921763B2

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