Trifluoroacetic acid methylene chloride → HCID 178488236, Verbindung

HRID 897753

Reaktionsgleichung

Reaktionsgleichung von HRID 897753
FC(F)(F)C(O)=O.ClCCl.[NH2:11][C:12]1[N:17]=[CH:16][N:15]=[C:14]2[N:18]([C@H:38]3[CH2:43][CH2:42][C@H:41]([N:44]4[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]4)[CH2:40][CH2:39]3)[N:19]=[C:20]([C:21]3[C:26]([F:27])=[CH:25][C:24]([NH:28]C(=O)OC(C)(C)C)=[C:23]([O:36][CH3:37])[CH:22]=3)[C:13]=12>ClCCl>[NH2:28][C:24]1[C:23]([O:36][CH3:37])=[CH:22][C:21]([C:20]2[C:13]3[C:14](=[N:15][CH:16]=[N:17][C:12]=3[NH2:11])[N:18]([C@H:38]3[CH2:43][CH2:42][C@H:41]([N:44]4[CH2:45][CH2:46][N:47]([CH3:50])[CH2:48][CH2:49]4)[CH2:40][CH2:39]3)[N:19]=2)=[C:26]([F:27])[CH:25]=1

Komponenten

4

Edukt 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 178488238HCID 178488238, Verbindung

Produkt 1

HCID 178488236HCID 178488236, VerbindungAusbeute 87,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of trifluoroacetic acid/dichloromethane (20:80, 7 mL) was added to a solution of trans-tert-butyl N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-5-fluoro-2-methoxyphenyl)carbamate (250 mg, 0.451 mmol) in dichloromethane (4.0 mL) at 0° C. After 15 minutes, the ice-bath was removed and the reaction mixture was stirred at room temperature for 4 hours. Solvent was then evaporated and the residue was dissolved in dichloromethane. Saturated sodium bicarbonate was added to adjust the pH to 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 give trans-3-(4-amino-2-fluoro-5-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (179 mg, 87%). 1H NMR (CDCl3) δ 1.56 (m, 2H), 2.15 (m, 7H), 2.31 (s, 3H), 2.51 (m, 4H), 2.67 (m, 4H), 3.88 (s, 3H), 4.16 (bs, 2H), 4.74 (m, 1H), 5.64 (bs, 2H), 6.56 (d, J=10.84 Hz, 1H), 6.88 (d, J=6.55 Hz, 1H), 8.33 (s, 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+=455.2, Rt=0.63 min.

Aufarbeitung

  1. customthe ice-bath was removed
  2. customSolvent was then evaporated
  3. dissolutionthe residue was dissolved in dichloromethane
  4. additionSaturated sodium bicarbonate was added
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with dichloromethane
  7. washThe combined organic layer was washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated

Quellen und Nachweise

ORD-Eintrag
ord-6ae497e7ac624396a3c6a3235feb9918
Quelldatensatz
uspto-grants-2005_07
Patentnummer
US06921763B2

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