Potassium Hydroxide → HCID 49846225、化合物

HRID 1930160ノート

反応式

HRID 1930160 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[C:23]([F:24])=[CH:22][C:21]([CH:25]([CH3:30])[C:26]([O:28]C)=[O:27])=[CH:20][C:19]=3[F:31])=[CH:14][CH:13]=2)[C:9]([CH3:32])=[N:8][C:7]=1[CH3:33])(=[O:5])[NH2:4]>CC(O)(C)C>[C:3]([C:6]1[N:11]=[C:10]([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[C:23]([F:24])=[CH:22][C:21]([CH:25]([CH3:30])[C:26]([OH:28])=[O:27])=[CH:20][C:19]=3[F:31])=[CH:16][CH:17]=2)[C:9]([CH3:32])=[N:8][C:7]=1[CH3:33])(=[O:5])[NH2:4]

参加物

4

反応物 2

HCID 14797Potassium HydroxideHCID 59627653HCID 59627653、化合物2 回

生成物 1

HCID 49846225HCID 49846225、化合物収率 54.8%

試薬・触媒・溶媒 1

HCID 6386tert-Butanol溶媒

反応条件

温度
45 °C

実験手順

Potassium hydroxide (0.396 g, 7.05 mmol) was added in one portion to methyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,6-difluorobiphenyl-4-yl)propanoate (Intermediate 21-1; 1 g, 2.35 mmol) in t-BuOH (15.16 mL) at room temperature. The resulting solution was stirred at 45° C. for 5 hours, a precipitate formed. The reaction mixture was quenched with 2M HCl (5 mL), evaporated to dryness and redissolved in water (10 mL), filtered through nylon, washed with water and dried under vacuum to afford product as a white solid. The 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% formic acid) and MeCN/MeOH as eluents. Fractions containing the desired compound were evaporated to dryness to afford 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2,6-difluorobiphenyl-4-yl)propanoic acid (0.530 g, 54.8%) as a white powder.

後処理

  1. customa precipitate formed
  2. customThe reaction mixture was quenched with 2M HCl (5 mL)
  3. customevaporated to dryness
  4. dissolutionredissolved in water (10 mL)
  5. filtrationfiltered through nylon
  6. washwashed with water
  7. customdried under vacuum
  8. customto afford product as a white solid
  9. customThe product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5μ silica, 50 mm diameter, 150 mm length)
  10. additionFractions containing the desired compound
  11. customwere evaporated to dryness

出典と根拠

ORDレコード
ord-87bd6f69b90c4c559f96a1a29b8722f8
出典データセット
uspto-grants-2012_05
特許番号
US08188092B2

反応ノート

読み込み中…