Potassium Hydroxide → 2-(2-(4'-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)-2-methylpropanoic acid

HRID 1930147ノート

反応式

HRID 1930147 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]([CH2:24][C:25]([NH:27][C:28]([CH3:34])([CH3:33])[C:29]([O:31]C)=[O:30])=[O:26])=[CH:20][C:19]=3[Cl:35])=[CH:14][CH:13]=2)[C:9]([CH3:36])=[N:8][C:7]=1[CH3:37])(=[O:5])[NH2:4]>CC(O)(C)C>[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]([CH2:24][C:25]([NH:27][C:28]([CH3:33])([CH3:34])[C:29]([OH:31])=[O:30])=[O:26])=[CH:20][C:19]=3[Cl:35])=[CH:14][CH:13]=2)[C:9]([CH3:36])=[N:8][C:7]=1[CH3:37])(=[O:5])[NH2:4]

参加物

4

反応物 2

HCID 14797Potassium HydroxideHCID 67286270Methyl 2-(2-(4'-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)-2-methylpropanoate2 回

生成物 1

HCID 498173702-(2-(4'-(6-Carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)-2-methylpropanoic acid収率 5.86%

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 (109 mg, 1.94 mmol) was added in one portion to methyl 2-(2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)-2-methylpropanoate (Intermediate 14-1; 319.5 mg, 0.65 mmol) in t-BuOH (4164 μL) at room temperature. The resulting solution was stirred at 45° C. for 5 hours and a precipitate formed. The reaction mixture was quenched with 2M HCl (5 mL), The reaction mixture was evaporated to dryness and redissolved in water (10 mL), and filtered through nylon, washed with water and dried under vacuum. 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% formic acid) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 2-(2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetamido)-2-methylpropanoic acid (18.20 mg, 5.86%) as a white solid.

後処理

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

出典と根拠

ORDレコード
ord-194f6b60ed3e496a85d44a191acea2b8
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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