Acetic Acid → 3-{4-[(2-furylmethyl)amino]-3-methoxyphenyl}-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine

HRID 432418Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 432418
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[N:14][C:15]=3[NH2:17])[N:10]([CH:18]3[CH2:23][CH2:22][N:21]([CH:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:20][CH2:19]3)[N:9]=2)=[CH:4][C:3]=1[O:31][CH3:32].[O:33]1[CH:37]=[CH:36][CH:35]=[C:34]1[CH:38]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.C(=O)(O)[O-].[Na+]>ClCCCl>[O:33]1[CH:37]=[CH:36][CH:35]=[C:34]1[CH2:38][NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[N:12][CH:13]=[N:14][C:15]=3[NH2:17])[N:10]([CH:18]3[CH2:23][CH2:22][N:21]([CH:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[CH2:20][CH2:19]3)[N:9]=2)=[CH:4][C:3]=1[O:31][CH3:32]

Komponenten

7

Edukt 5

HCID 176Acetic AcidHCID 7362FurfuralHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 223469753-(4-amino-3-methoxyphenyl)-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Produkt 1

HCID 223473653-{4-[(2-furylmethyl)amino]-3-methoxyphenyl}-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amineAusbeute 48,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 111,2-DichloroethaneLösungsmittel

Versuchsvorschrift

3-(4-Amino-3-methoxyphenyl)-1-[1-(1-methylpiperidin-4-yl)-piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (100 mg, 0.229 mmol), 2-furaldehyde (0.027 mL, 0.321 mmol), sodium triacetoxyborohydride (193 mg, 0.916 mmol) and glacial acetic acid (55 mg, 0.916 mmol) were mixed with 1,2-dichloroethane (5 mL). The reaction mixture was stirred at room temperature overnight. Saturated sodium bicarbonate solution was added to adjust the pH to about 8. The layers were separated and 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/ammonium hydroxide (95:5:0.2) as mobile phase to give 3-{4-[(2-furylmethyl)amino]-3-methoxyphenyl}-1-[1-(1-methylpiperidin-4-yl)piperidin-4-yl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (57 mg, 48%). 1H NMR (DMSO-d6) 6 1.45 (m, 2H), 1.71 (m, 2H), 1.87 (m, 4H), 2.14 (s, 3H), 2.28 (m, 5H), 2.80 (m, 2H), 3.01 (m, 2H), 3.86 (s, 1H), 4.37 (d, J=3.13, 1H), 6.76 (d, J=8.62, 1H), 7.07 (m, 2H), 7.57 (s, 1H), 8.19 (s, 1H). LCMS (Finigan-Column: Pecosphere, C18, 3 um, 33×4.6 mm. Eluents: 0% B/A to 100% B/A in 4 min. (B: acetonitrile, A: 50 mM ammonia acetate buffer, pH 4.5), 3.0 mL/min.): MH+ 517.3, Rt=2.28 min.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-6f29c3d69f684d338c89890646c93369
Quelldatensatz
uspto-grants-2003_12
Patentnummer
US06660744B1

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