Triethylamine → 2-[3-Cyclopentyl-2-(4-phenoxy-phenyl)-propionylamino]-thiazole-4-carboxylic acid ethyl ester

HRID 1935224노트

반응식

HRID 1935224 반응식
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:24]([O:26][C:27]([C:29]1[N:30]=[C:31]([NH2:34])[S:32][CH:33]=1)=[O:28])[CH3:25].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>C(Cl)Cl.O>[CH2:24]([O:26][C:27]([C:29]1[N:30]=[C:31]([NH:34][C:8](=[O:9])[CH:7]([C:11]2[CH:12]=[CH:13][C:14]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:15][CH:16]=2)[CH2:6][CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[S:32][CH:33]=1)=[O:28])[CH3:25]

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 73216Ethyl 2-aminothiazole-4-carboxylateHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 224679293-Cyclopentyl-2-(4-phenoxy-phenyl)propionic acid

생성물 1

HCID 865841372-[3-Cyclopentyl-2-(4-phenoxy-phenyl)-propionylamino]-thiazole-4-carboxylic acid ethyl ester수율 49.2%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

반응 조건

온도
25 °C

실험 절차

A solution of 3-cyclopentyl-2-(4-phenoxy-phenyl)-propionic acid (prepared in Example 12A, 767 mg, 2.47 mmol) in methylene chloride (20 mL) at 25° C. was treated with 2-amino-thiazole-4-carboxylic acid ethyl ester (553 mg, 3.21 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (1.64 g, 3.71 mmol), and triethylamine (1 mL, 7.41 mmol). The resulting reaction mixture was stirred at 25° C. for 16 h. The reaction mixture was then diluted with water (10 mL) and then extracted with methylene chloride (3×15 mL). The combined organic extracts were washed with a 1N aqueous sodium hydroxide solution (1×10 mL), a 1N aqueous hydrochloric acid solution (1×10 mL), and a saturated aqueous sodium chloride solution (1×10 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 90/10 hexanes/ethyl acetate) afforded 2-[3-cyclopentyl-2-(4-phenoxy-phenyl)-propionylamino]-thiazole-4-carboxylic acid ethyl ester (564 mg, 49%) as a white foam: FAB-HRMS m/e calcd for C26H28N2O4S (M+H)+ 465.1848, found 465.1831.

후처리

  1. customThe resulting reaction mixture
  2. extractionextracted with methylene chloride (3×15 mL)
  3. washThe combined organic extracts were washed with a 1N aqueous sodium hydroxide solution (1×10 mL)
  4. dry with materialThe organic layer was then dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-6d81fba93c03402ca951e925bbccd66e
출처 데이터셋
uspto-grants-2002_05
특허 번호
US06384220B2

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