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

HRID 1986096노트

반응식

HRID 1986096 반응식
[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

참가 물질

6

반응물 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 salt2회HCID 690653125-Bromo-N-(2,4-difluorophenyl)-2-fluoronicotinamide

생성물 1

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

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
110 °C

실험 절차

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)+.

후처리

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

출처 및 근거

ORD 기록
ord-255cfb3dbb544e94b2841f9bbb086698
출처 데이터셋
uspto-grants-2009_06
특허 번호
US07547782B2

반응 노트

불러오는 중…