Hydrochloric Acid → 2-(4-(1h-Pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorophenylamino)-5-bromo-n-(2,4-difluorophenyl)nicotinamide, dihydrochloride salt

HRID 1986096Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1986096
[ClH:1].[NH:2]1[C:6]2=[N:7][CH:8]=[CH:9][C:10]([O:11][C:12]3[CH:17]=[CH:16][C:15]([NH:18]C4C(C(NC5C=CC(F)=CC=5F)=O)=CN=CC=4)=[CH:14][C:13]=3[F:36])=[C:5]2[CH:4]=[CH:3]1.[Br:37][C:38]1[CH:39]=[N:40][C:41](F)=[C:42]([CH:54]=1)[C:43]([NH:45][C:46]1[CH:51]=[CH:50][C:49]([F:52])=[CH:48][C:47]=1[F:53])=[O:44].Cl.O1CCOCC1>CN1C(=O)CCC1>[ClH:1].[ClH:1].[NH:2]1[C:6]2=[N:7][CH:8]=[CH:9][C:10]([O:11][C:12]3[CH:17]=[CH:16][C:15]([NH:18][C:41]4[N:40]=[CH:39][C:38]([Br:37])=[CH:54][C:42]=4[C:43]([NH:45][C:46]4[CH:51]=[CH:50][C:49]([F:52])=[CH:48][C:47]=4[F:53])=[O:44])=[CH:14][C:13]=3[F:36])=[C:5]2[CH:4]=[CH:3]1

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 162230054-(4-(1h-Pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorophenylamino)-n-(2,4-difluorophenyl)nicotinamide, hydrochloride salt2×HCID 690653125-Bromo-N-(2,4-difluorophenyl)-2-fluoronicotinamide

Produkt 1

HCID 1317274872-(4-(1h-Pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorophenylamino)-5-bromo-n-(2,4-difluorophenyl)nicotinamide, dihydrochloride salt

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

To a solution of 4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluoroaniline (17 mg, 0.07 mmol, Compound C of Example 1) and 5-bromo-N-(2,4-difluorophenyl)-2-fluoronicotinamide (26 mg, 0.08 mmol) in 1 mL of NMP was added 4N HCl in 1,4-dioxane (0.05 mL, 0.20 mmol). The mixture was stirred at 110° C. for 4 d. After cooling, the mixture was purified on preparative (RP) HPLC to give fractions containing the desired product. The fractions were pooled and concentrated in vacuo and the residue was treated with 10 mL of 1N HCl and it was concentrated again to give the title compound (8.0 mg, 18% yield). 1H NMR (DMSO-d6) δ 10.66 (s, 1H), 10.62 (s, 1H), 8.55 (d, 2H, J=7.5 Hz), 8.06 (d, 1H, J=13.4 Hz), 7.35-7.62 (m, 5H), 7.16 (m, 1H), 6.62 (d, 1H, J=6.0 Hz), 6.43 (s, 1H); MS(ESI+) m/z 554.15, 556.14 (M+H)+.

Aufarbeitung

  1. temperatureAfter cooling
  2. customthe mixture was purified on preparative (RP) HPLC
  3. customto give fractions

Quellen und Nachweise

ORD-Eintrag
ord-255cfb3dbb544e94b2841f9bbb086698
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07547782B2

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