Hydrochloric Acid → HCID 90229263、化合物

HRID 1505789ノート

反応式

HRID 1505789 の反応式
CC(C)([O-])C.[K+].[CH:7]([O:10][CH2:11][CH2:12][OH:13])([CH3:9])[CH3:8].[Cl:14][C:15]1[CH:23]=[CH:22][C:21](F)=[CH:20][C:16]=1[C:17]([OH:19])=[O:18].Cl>CN1C(=O)CCC1.O>[Cl:14][C:15]1[CH:23]=[CH:22][C:21]([O:13][CH2:12][CH2:11][O:10][CH:7]([CH3:9])[CH3:8])=[CH:20][C:16]=1[C:17]([OH:19])=[O:18]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 7996IsopropylethanediolHCID 3028882-Chloro-5-fluorobenzoic acidHCID 23665647Potassium tert-butoxide

生成物 1

HCID 90229263HCID 90229263、化合物

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

Under argon atmosphere, potassium tert-butoxide (168 mg) was added to a solution of 2-isopropoxyethanol (172 μL) in NMP (1.5 mL). The mixture was stirred at room temperature for 10 minutes, 2-chloro-5-fluorobenzoic acid (87 mg) was added, and it was then stirred at 130° C. for 4 hours. The reaction mixture was cooled on ice bath, water was added, and it was then acidified with 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was separated, washed with brine, and dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain crude 2-chloro-5-[2-(propan-2-yloxy)ethoxy]benzoic acid. This was dissolved in DMF (2 mL), HATU (61 mg), N,N-diisopropylethylamine (29 μL) and 6-amino-N-(3-chloro-2-methylphenyl)-2-(methoxymethyl)-1H-benzimidazole-4-carboxamide (50 mg) were added in this order, and it was stirred at room temperature for 12 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 N-(3-chloro-2-methylphenyl)-6-[({2-chloro-5-[2-(propan-2-yl oxy)ethoxy]phenyl}carbonyl)amino]-2-(methoxymethyl)-1H-benz imidazole-4-carboxamide (41 mg) as white powder. 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 (28 mg) as white powder.

後処理

  1. stirringit was then stirred at 130° C. for 4 hours
  2. temperatureThe reaction mixture was cooled on ice bath
  3. extractionextracted with ethyl acetate
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-0bd9d134a90242e1a2869574fe534247
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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