Diisopropylethylamine → 6-{[(2-bromo-6-fluorophenyl) carbonyl]amino}-N-(3-chloro-2-m ethylphenyl)-2-(methoxymethyl)-1H-benzimidazole-4-carboxamide

HRID 1505788ノート

反応式

HRID 1505788 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([C:14]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=2[CH3:24])=[O:15])[C:5]2[N:9]=[C:8]([CH2:10][O:11][CH3:12])[NH:7][C:6]=2[CH:13]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[Br:58][C:59]1[CH:67]=[CH:66][CH:65]=[C:64]([F:68])[C:60]=1[C:61](O)=[O:62].C(=O)(O)[O-].[Na+]>CN(C=O)C>[Br:58][C:59]1[CH:67]=[CH:66][CH:65]=[C:64]([F:68])[C:60]=1[C:61]([NH:1][C:2]1[CH:3]=[C:4]([C:14]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=2[CH3:24])=[O:15])[C:5]2[N:9]=[C:8]([CH2:10][O:11][CH3:12])[NH:7][C:6]=2[CH:13]=1)=[O:62]

参加物

7

反応物 5

HCID 81531DiisopropylethylamineHCID 3026212-Bromo-6-fluorobenzoic acidHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 902293686-amino-N-(3-chloro-2-methylphenyl)-2-(methoxymethyl)-1H-benzimidazole-4-carboxamide

生成物 1

HCID 715321486-{[(2-bromo-6-fluorophenyl) carbonyl]amino}-N-(3-chloro-2-m ethylphenyl)-2-(methoxymethyl)-1H-benzimidazole-4-carboxamide収率 58.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 6-amino-N-(3-chloro-2-methylphenyl)-2-(methoxymethyl)-1H-benzimidazole-4-carboxamide (50 mg) in DMF (1.5 mL), were added HBTU (66 mg), N,N-diisopropylethylamine (30 μL) and 2-bromo-6-fluorobenzoic acid (38 mg) in turn, and the mixture was stirred at room temperature for 24 hours. The reaction mixture was poured into saturated aqueous sodium bicarbonate, and extracted with ethyl acetate. The organic layer was separated, washed sequentially with water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified on column chromatography to obtain 6-{[(2-bromo-6-fluorophenyl) carbonyl]amino}-N-(3-chloro-2-m ethylphenyl)-2-(methoxymethyl)-1H-benzimidazole-4-carboxamide (46 mg). This was dissolved in ethyl acetate (2 mL), and treated with 4N hydrogen chloride/ethyl acetate (1.2 Eq). The precipitate was collected by filtration, and dried to obtain the titled compound (24 mg) as white powder.

後処理

  1. extractionextracted with ethyl acetate
  2. customThe organic layer was separated
  3. washwashed sequentially with water and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified on column chromatography

出典と根拠

ORDレコード
ord-4a731dc1f1b94665aec5fb6a9b6dd627
出典データセット
uspto-grants-2015_12
特許番号
US09216968B2

反応ノート

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