Potassium Carbonate → HCID 178493017, Verbindung

HRID 1014431Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1014431
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]2[C:13]3[CH:38]=[CH:37][N:36](S(C4C=CC(C)=CC=4)(=O)=O)[C:14]=3[N:15]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:30][CH2:29][N:28]([CH:31]([CH3:33])[CH3:32])[CH2:27][CH2:26]4)=[CH:21][C:20]=3[O:34][CH3:35])[N:17]=2)[C:3]=1[C:4]([NH2:6])=[O:5].C([O-])([O-])=O.[K+].[K+]>CO.O1CCCC1>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]2[N:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:26][CH2:27][N:28]([CH:31]([CH3:33])[CH3:32])[CH2:29][CH2:30]4)=[CH:21][C:20]=3[O:34][CH3:35])[NH:15][C:14]3=[N:36][CH:37]=[CH:38][C:13]=23)[C:3]=1[C:4]([NH2:6])=[O:5]

Komponenten

5

Edukt 2

HCID 11430Potassium CarbonateHCID 594420752-fluoro-6-({2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide

Produkt 1

HCID 178493017HCID 178493017, VerbindungAusbeute 92,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

To a suspension of the 2-fluoro-6-({2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)benzamide (15.7 g, 23.4 mmol) in methanol (250 mL) and tetrahydrofuran (125 ml) was added K2CO3 (32.3g 234 mmol in 125 ml of water), The reaction mixture was stirred at 85° C. for 6 hours. The organic layer was subsequently washed with water and brine, dried over sodium sulfate, filtered, stripped onto celite, and purified by chromatography on SiO2 (400 g SiO2, 0% to 10% MeOH/CH2CL2 with 0.1% added NH3) to afford the 2-fluoro-6-[(2-{[4-[4-(1-methylethyl)-1-piperazinyl]-2-(methyloxy)phenyl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]benzamide (11.2 g, 92%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.01 (d, J=6.59 Hz, 6 H), 2.59 (d, J=3.85 Hz, 4 H), 2.67 (m, J=6.41 Hz, 1 H), 3.10 (br. s., 4 H), 3.81 (s, 3H), 6.22 (s., 1 H), 6.47 (d, J=8.79 Hz, 1 H), 6.63 (d, J=1.28 Hz, 1 H), 6.89-6.98 (m, 2 H), 7.36-7.46 (m, 2 H), 7.90 (d, J=8.61 Hz, 1 H), 8.02 (s., 1 H), 8.10 (s, 1 H), 8.50 (d, J=8.42 Hz, 1 H), 10.47 (s, 1 H), 11.31 (s., 1 H). MS(ESI): m/z 519 (M+1)+.

Aufarbeitung

  1. washThe organic layer was subsequently washed with water and brine
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. custompurified by chromatography on SiO2 (400 g SiO2, 0% to 10% MeOH/CH2CL2 with 0.1% added NH3)

Quellen und Nachweise

ORD-Eintrag
ord-5733a79047c64f4c883f1824e9f930f5
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07981903B2

Notizen zur Reaktion

Wird geladen…