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

HRID 1986096ノート

反応式

HRID 1986096 の反応式
[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

参加物

6

反応物 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 回HCID 690653125-Bromo-N-(2,4-difluorophenyl)-2-fluoronicotinamide

生成物 1

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

試薬・触媒・溶媒 1

HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
110 °C

実験手順

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)+.

後処理

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

出典と根拠

ORDレコード
ord-255cfb3dbb544e94b2841f9bbb086698
出典データセット
uspto-grants-2009_06
特許番号
US07547782B2

反応ノート

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