Triethylamine → N-(5-bromo-thiazol-2-yl)-3-cyclopentyl-2-(4-methanesulfonyl-phenyl)-propionamide

HRID 1355245

反応式

HRID 1355245 の反応式
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.Br.[NH2:28][C:29]1[S:30][C:31]([Br:34])=[CH:32][N:33]=1.C(N(CC)CC)C>CN(C)C=O.C(Cl)Cl>[Br:34][C:31]1[S:30][C:29]([NH:28][C:8](=[O:10])[CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][CH:12]=2)[CH2:6][CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5]2)=[N:33][CH:32]=1

参加物

8

反応物 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 27238485-Bromothiazol-2-amine monohydrobromideHCID 120694893-Cyclopentyl-2-(4-methanesulfonyl-phenyl)propionic acid

生成物 1

HCID 22315232N-(5-bromo-thiazol-2-yl)-3-cyclopentyl-2-(4-methanesulfonyl-phenyl)-propionamide収率 35%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide触媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

A solution of 3-cyclopentyl-2-(4-methanesulfonyl-phenyl)-propionic acid (prepared in Example 130, 300 mg, 1.01 mmol) and dry N,N-dimethylformamide (2 drops) in methylene chloride (3 mL) was cooled to 0° C. and then treated dropwise with oxalyl chloride (115 μL, 1.32 mmol). The reaction mixture was stirred at 0° C. for 10 min and then stirred at 25° C. for 1 h. The reaction mixture was concentrated in vacuo. The resulting yellow oil was dissolved in a small amount of methylene chloride and then slowly added to a solution of 2-amino-5-bromothiazole monohydrobromide (395 mg, 1.52 mmol) and triethylamine (424 μL, 3.04 mmol) in N,N-dimethylformamide (3 mL). The resulting reaction mixture was then stirred at 25° C. for 15 h. The resulting reaction mixture was partitioned between water (50 mL) and ethyl acetate (50 mL), and the layers were separated. The aqueous layer was further extracted with ethyl acetate (50 mL). The combined organic layers were then dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 1/1 hexanes/ethyl acetate) afforded the N-(5-bromo-thiazol-2-yl)-3-cyclopentyl-2-(4-methanesulfonyl-phenyl)-propionamide (160 mg, 35%) as a tan foam: mp 73–75° C. (foam to gel); EI-HRMS m/e calcd for C18H21BrN2O3S2 (M+) 456.0177, found 456.0176.

後処理

  1. stirringstirred at 25° C. for 1 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. dissolutionThe resulting yellow oil was dissolved in a small amount of methylene chloride
  4. customThe resulting reaction mixture
  5. stirringwas then stirred at 25° C. for 15 h
  6. customThe resulting reaction mixture
  7. customwas partitioned between water (50 mL) and ethyl acetate (50 mL)
  8. customthe layers were separated
  9. extractionThe aqueous layer was further extracted with ethyl acetate (50 mL)
  10. dry with materialThe combined organic layers were then dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-390f215c9cc14b7caed7d7d15ef0704a
出典データセット
uspto-grants-2007_05
特許番号
US07223868B2

関連ノート

読み込み中…