Hydrochloric Acid → 1-(4'-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)cyclopropanecarboxylic acid

HRID 1930140ノート

反応式

HRID 1930140 の反応式
[OH-].[K+].[C:3]([C:6]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([C:27]([O:29]C)=[O:28])[CH2:26][CH2:25]4)=[CH:20][C:19]=3[Cl:31])=[CH:14][CH:13]=2)[C:9]([CH3:32])=[N:8][C:7]=1[CH3:33])(=[O:5])[NH2:4].Cl>C(O)(C)(C)C>[C:3]([C:6]1[N:11]=[C:10]([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([C:27]([OH:29])=[O:28])[CH2:25][CH2:26]4)=[CH:20][C:19]=3[Cl:31])=[CH:16][CH:17]=2)[C:9]([CH3:32])=[N:8][C:7]=1[CH3:33])(=[O:5])[NH2:4]

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 59627667Methyl 1-(4'-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)cyclopropanecarboxylate2 回

生成物 1

HCID 498461431-(4'-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)cyclopropanecarboxylic acid収率 22.96%

試薬・触媒・溶媒 1

HCID 6386tert-Butanol溶媒

反応条件

温度
45 °C

実験手順

Powdered potassium hydroxide (52.1 mg, 0.93 mmol) was added in one portion to methyl 1-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)cyclopropanecarboxylate (Intermediate 10-1; 135 mg, 0.31 mmol) in tert-butanol (5 mL) at 45° C. The resulting solution was stirred at 45° C. for 30 minutes. 2N HCl (1 mL) was added and the mixture was evaporated to remove the organic solvent. The suspension was collected by filtration, washed with water and dried under vacuum to afford crude product. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 0.1% TFA) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 1-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)cyclopropanecarboxylic acid (30.0 mg, 22.96%) as a white solid.

後処理

  1. customthe mixture was evaporated
  2. customto remove the organic solvent
  3. filtrationThe suspension was collected by filtration
  4. washwashed with water
  5. customdried under vacuum
  6. customto afford crude product
  7. customThe crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length)
  8. additionFractions containing the desired compound
  9. customwere evaporated to dryness

出典と根拠

ORDレコード
ord-a4dfce23b0654f29a978f9afeb86d735
出典データセット
uspto-grants-2012_05
特許番号
US08188092B2

反応ノート

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