Formic Acid → 6-Chloro-2-ethyl-5-(methylamino)-1-(4-{2-[({[(4-methylphenyl)sulfonyl]amino}carbonyl)amino]ethyl}phenyl)-1H-benzimidazole

HRID 50457ノート

反応式

HRID 50457 の反応式
[C:1](OC(=O)C)(=O)C.C(O)=O.[Cl:11][C:12]1[C:13]([NH:45]S(C)(=O)=O)=[CH:14][C:15]2[N:19]=[C:18]([CH2:20][CH3:21])[N:17]([C:22]3[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][NH:30][C:31]([NH:33][S:34]([C:37]4[CH:42]=[CH:41][C:40]([CH3:43])=[CH:39][CH:38]=4)(=[O:36])=[O:35])=[O:32])=[CH:24][CH:23]=3)[C:16]=2[CH:44]=1>C1COCC1>[Cl:11][C:12]1[C:13]([NH:45][CH3:1])=[CH:14][C:15]2[N:19]=[C:18]([CH2:20][CH3:21])[N:17]([C:22]3[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][NH:30][C:31]([NH:33][S:34]([C:37]4[CH:38]=[CH:39][C:40]([CH3:43])=[CH:41][CH:42]=4)(=[O:36])=[O:35])=[O:32])=[CH:24][CH:23]=3)[C:16]=2[CH:44]=1

参加物

5

反応物 3

HCID 284Formic AcidHCID 7918Acetic AnhydrideHCID 21875777HCID 21875777、化合物

生成物 1

HCID 218758116-Chloro-2-ethyl-5-(methylamino)-1-(4-{2-[({[(4-methylphenyl)sulfonyl]amino}carbonyl)amino]ethyl}phenyl)-1H-benzimidazole収率 67%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
60 °C

実験手順

A solution of acetic anhydride (0.14 ml) in THF (5 ml) was added formic acid (0.06 ml, 1.65 mmol) at 0° C. under nitrogen and the mixture was stirred at 60° C. for 2 h. Then the mixture was recooled to 0° C. and was added 6-Chloro-1-[4-(2-chloroethyl)phenyl]-2-ethyl-1H-benzimidazol-5-ylamine (Example 110, step 6, 100 mg, 0.3 mmol) in THF (2 ml). The mixture was stirred at room temperature for 2 h. The volatile component was removed under reduced pressure, and the residue was dissolved with ethyl acetate (100 ml). The organic layer was washed with 2N aqueous NaOH (50 ml), brine (50 ml), then dried (Na2SO4). After removal of solvent, the crude product was purified by flash column chromatography eluting with hexane/ethyl acetate (1:10) to afford 68 mg (67%) of the title compound as pale yellow solids.

後処理

  1. customwas recooled to 0° C.
  2. stirringThe mixture was stirred at room temperature for 2 h
  3. customThe volatile component was removed under reduced pressure
  4. dissolutionthe residue was dissolved with ethyl acetate (100 ml)
  5. washThe organic layer was washed with 2N aqueous NaOH (50 ml), brine (50 ml)
  6. dry with materialdried (Na2SO4)
  7. customAfter removal of solvent
  8. customthe crude product was purified by flash column chromatography
  9. washeluting with hexane/ethyl acetate (1:10)

出典と根拠

ORDレコード
ord-d0e53ee7a6bb46009e2cbc7a5aebdd8c
出典データセット
uspto-grants-2004_03
特許番号
US06710054B2

反応ノート

読み込み中…