N-bromobutanimide → 3-[3-(2-chloro-4-pyrimidinyl)-7-fluoroimidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluoro-phenyl)benzamide

HRID 419578ノート

反応式

HRID 419578 の反応式
[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([C:11]2[CH:12]=[C:13]([CH:25]=[CH:26][CH:27]=2)[C:14]([NH:16][C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])=[O:15])=O)[CH:5]=[CH:4][N:3]=1.C1C(=O)N(Br)C(=O)C1.[F:36][C:37]1[CH:42]=[CH:41][N:40]=[C:39]([NH2:43])[CH:38]=1>C(Cl)Cl.CCOC(C)=O.C([O-])(O)=O.[Na+]>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[N:40]3[CH:41]=[CH:42][C:37]([F:36])=[CH:38][C:39]3=[N:43][C:9]=2[C:11]2[CH:12]=[C:13]([CH:25]=[CH:26][CH:27]=2)[C:14]([NH:16][C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])=[O:15])[CH:5]=[CH:4][N:3]=1

参加物

7

反応物 3

HCID 67184N-bromobutanimideHCID 183278082-Amino-4-fluoropyridineHCID 598602583-[(2-Chloro-4-pyrimidinyl)acetyl]-N-(2,6-difluorophenyl)benzamide

生成物 1

HCID 594529173-[3-(2-chloro-4-pyrimidinyl)-7-fluoroimidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluoro-phenyl)benzamide収率 55%

試薬・触媒・溶媒 3

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
75 °C

実験手順

To a stirred solution of 3-[(2-chloro-4-pyrimidinyl)acetyl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1, step B) (0.6 g, 1.49 mmol) in DCM (15 mL) at rt under N2 was added NBS (0.278 g, 1.56 mmol). The reaction was stirred approximately 60 min, then concentrated under vacuum to a foam like solid. The solid was dissolved in dioxane (15 mL) and 4-fluoro-2-pyridinamine (0.5 g, 4.46 mmol) was added. The reaction was stirred under N2, heated to 75° C., and stirred for approximately 18 h, then cooled to rt. The reaction was diluted with EtOAc and half-saturated aqueous NaHCO3. The organic layer was separated and washed with brine. The combined aqueous layers were extracted with EtOAc (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography to give the title compound of step B (0.391 g, 0.81 mmol, 55%) as a light yellow solid. MS (ESI): 480 [M+H]+.

後処理

  1. concentrationconcentrated under vacuum to a foam like solid
  2. dissolutionThe solid was dissolved in dioxane (15 mL)
  3. stirringThe reaction was stirred under N2
  4. stirringstirred for approximately 18 h
  5. temperaturecooled to rt
  6. customThe organic layer was separated
  7. washwashed with brine
  8. extractionThe combined aqueous layers were extracted with EtOAc (3×)
  9. dry with materialThe combined organic layers were dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under vacuum
  12. customThe residue was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-997da2507171408cb055d348193c7452
出典データセット
uspto-grants-2012_01
特許番号
US08093239B2

反応ノート

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