Acetic Acid → 1-[1-(1-methyl-4-piperidyl)tetrahydro-1H-3-pyrrolyl]-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 432292Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 432292
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[N:20][C:21]=3[NH2:23])[N:16]([CH:24]3[CH2:28][CH2:27][NH:26][CH2:25]3)[N:15]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:29][N:30]1[CH2:35][CH2:34][C:33](=O)[CH2:32][CH2:31]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.C(=O)(O)[O-].[Na+]>ClCCCl>[CH3:29][N:30]1[CH2:35][CH2:34][CH:33]([N:26]2[CH2:27][CH2:28][CH:24]([N:16]3[C:17]4=[N:18][CH:19]=[N:20][C:21]([NH2:23])=[C:22]4[C:14]([C:11]4[CH:10]=[CH:9][C:8]([O:1][C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)=[CH:13][CH:12]=4)=[N:15]3)[CH2:25]2)[CH2:32][CH2:31]1

Komponenten

7

Edukt 5

HCID 176Acetic AcidHCID 740491-Methyl-4-piperidoneHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 22346899HCID 22346899, Verbindung

Produkt 1

HCID 223470641-[1-(1-methyl-4-piperidyl)tetrahydro-1H-3-pyrrolyl]-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amineAusbeute 78,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 111,2-DichloroethaneLösungsmittel

Versuchsvorschrift

3-(4-Phenoxyphenyl)-1-tetrahydro-1H-3-pyrrolyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (150 mg, 0.403 mmol), 1-methyl-4-piperidone (0.099 mL, 0.806 mmol), sodium triacetoxyborohydride (113 mg, 0.537 mmol) and glacial acetic acid (48 mg, 0.806 mmol) were mixed with 1,2-dichloroethane (4 mL). The reaction mixture was stirred at room temperature for 6 hours and saturated sodium bicarbonate solution was added to adjust the pH to about 9. The aqueous layer was extracted with dichloromethane. The combined organic layer was washed with brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (85:15) as mobile phase to give 1-[1-(1-methyl-4-piperidyl)tetrahydro-1H-3-pyrrolyl]-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (148 mg, 78%). 1H NMR (DMSO-d6) δ 1.42 (m, 2H), 1.81 (m, 2H), 1.92 (m, 2H), 2.15 (m, 1H), 2.26 (m, 2, 3H), 2.28 (m, 2H), 2.75 (m, 4H), 2.86 (m, 1H), 3.22 (m, 1H), 5.36 (m, 1H), 7.16 (m, 5H), 7.44 (m, 2H), 7.67 (m, 2H), 8.24 (s, 1H). LCMS (Micromass-Column: Pecosphere, C18, 3 um, 33×4.6 mm. Eluents: 0% B/A to 100% B/A in 4.5 min.(B: acetonitrile, A: 50 mM ammonia acetate buffer, PH 4.5), 3.5 mL/min.): MH+ =470.4, Rt=2.01.

Aufarbeitung

  1. extractionThe aqueous layer was extracted with dichloromethane
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-7f95f2e0154e4784beafdc543d73ddd7
Quelldatensatz
uspto-grants-2003_12
Patentnummer
US06660744B1

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