Phenyl Isothiocyanate → (RS) 3-{5-[2-(2-Phenylamino-benzoxazol-6-yl)-acetylamino]-pyridin-2-yl}-butyric acid

HRID 49699

反応式

HRID 49699 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH:11][C:12]2[CH:13]=[CH:14][C:15]([CH:18]([CH3:24])[CH2:19][C:20]([O:22]C)=[O:21])=[N:16][CH:17]=2)=[O:10])=[CH:4][C:3]=1[OH:25].[C:26]1([N:32]=[C:33]=S)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C(O)C>[C:26]1([NH:32][C:33]2[O:25][C:3]3[CH:4]=[C:5]([CH2:8][C:9]([NH:11][C:12]4[CH:13]=[CH:14][C:15]([CH:18]([CH3:24])[CH2:19][C:20]([OH:22])=[O:21])=[N:16][CH:17]=4)=[O:10])[CH:6]=[CH:7][C:2]=3[N:1]=2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

参加物

4

反応物 2

HCID 7673Phenyl IsothiocyanateHCID 17946638(RS) Methyl 3-{5-[2-(4-amino-3-hydroxy-phenyl)-acetylamino]-pyridin-2-yl}-butanoate

生成物 1

HCID 9932413(RS) 3-{5-[2-(2-Phenylamino-benzoxazol-6-yl)-acetylamino]-pyridin-2-yl}-butyric acid

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒2 回

反応条件

温度
70 °C

実験手順

A solution of (RS) methyl 3-{5-[2-(4-amino-3-hydroxy-phenyl)-acetylamino]-pyridin-2-yl}-butyrate (41.2 mg, Reference Example 24) in ethanol (1 mL) was treated with a solution of phenyl isothiocyanate (16.23 mg) in ethanol (2 mL). The mixture allowed to stand at room temperature for 48 hours, then heated at 70° C. for 16 hours and then evaporated. The residue, (RS) methyl 3-{5-[2-(3-hydroxy-4-(3-phenylthioureido)-phenyl)-acetylamino]-pyridin-2-yl}-butyrate, was dissolved in dry dimethylformamide (1 mL) and the solution was treated with a solution of dicyclohexylcarbodiimide (74.2 mg) in dry dimethylformamide (2 mL). This mixture was heated at 70° C. for 12 hours and then evaporated. The residue was dissolved in methanol (2 mL) and the solution was treated with aqueous sodium hydroxide (600 μL, 1M). After shaking for 24 hours the mixture was filtered and the filtrate was acidified with aqueous acetic acid (1 mL, 1M). The precipitate was filtered and dissolved in dimethylformamide. This solution was evaporated and the residue was subjected to reversed phase HPLC on a Hypersil Elite C18 column (100 mm×21 mm) using 0.05% TFA in acetonitrile water to give the title compound. LC-MS: RT=2.36 minutes; MS (ES+): 431 (MH+).

後処理

  1. customevaporated
  2. dissolutionThe residue, (RS) methyl 3-{5-[2-(3-hydroxy-4-(3-phenylthioureido)-phenyl)-acetylamino]-pyridin-2-yl}-butyrate, was dissolved in dry dimethylformamide (1 mL)
  3. additionthe solution was treated with a solution of dicyclohexylcarbodiimide (74.2 mg) in dry dimethylformamide (2 mL)
  4. temperatureThis mixture was heated at 70° C. for 12 hours
  5. customevaporated
  6. dissolutionThe residue was dissolved in methanol (2 mL)
  7. additionthe solution was treated with aqueous sodium hydroxide (600 μL, 1M)
  8. filtrationwas filtered
  9. filtrationThe precipitate was filtered
  10. dissolutiondissolved in dimethylformamide
  11. customThis solution was evaporated

出典と根拠

ORDレコード
ord-f8d5ec0155544f74bdc4baec67ad2b40
出典データセット
uspto-grants-2004_03
特許番号
US06706738B2

関連ノート

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