Oxalyl chloride → 3-cyclopentyl-N-pyrimidin-4-yl-2-(3-trifluoromethyl-phenyl)-propionamide

HRID 398717

반응식

HRID 398717 반응식
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.C(N(CC)C(C)C)(C)C.[NH2:36][C:37]1[CH:42]=[CH:41][N:40]=[CH:39][N:38]=1>C(Cl)Cl.CN(C)C=O.O1CCCC1>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[C:8]([NH:36][C:37]2[CH:42]=[CH:41][N:40]=[CH:39][N:38]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

참가 물질

8

반응물 4

HCID 65578Oxalyl chlorideHCID 689584-AminopyrimidineHCID 81531DiisopropylethylamineHCID 223153293-Cyclopentyl-2-(3-trifluoromethyl-phenyl)-propionic acid

생성물 1

HCID 223150803-cyclopentyl-N-pyrimidin-4-yl-2-(3-trifluoromethyl-phenyl)-propionamide수율 88%

시약·촉매·용매 3

HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매2회HCID 8028Tetrahydrofuran용매

반응 조건

온도
0 °C

실험 절차

A solution of 3-cyclopentyl-2-(3-trifluoromethyl-phenyl)-propionic acid (prepared as in Example 88, 152 mg, 0.532 mmol) in methylene chloride (10 mL) was treated with dry N,N-dimethylformamide (3 drops). The reaction mixture was cooled to 0° C. and then treated dropwise with a 2M solution of oxalyl chloride in methylene chloride (0.30 mL, 0.58 mmol). The reaction mixture was stirred at 0° C. for 10 min and then stirred at 25° C. for 30 min. The reaction mixture was then treated with N,N-diisopropylethylamine (0.22 mL, 1.26 mmol) followed by a solution of 4-aminopyrimidine (106 mg, 1.12 mmol) in dry tetrahydrofuran (5 mL). The resulting reaction mixture was stirred at 25° C. for 17 h. The reaction mixture was concentrated in vacuo. The resulting residue was adsorbed onto silica gel (Merck Silica gel 60, 230-400 mesh) and then purified via Biotage chromatography (FLASH 40S, Silica, 1/1 hexanes/ethyl acetate) to afford 3-cyclopentyl-N-pyrimidin-4-yl-2-(3-trifluoromethyl-phenyl)-propionamide (170 mg, 88%) as a white solid: mp 113-115° C.;. EI-HRMS m/e calcd for C19H20F3N3O (M+) 363.1558, found 363.1553.

후처리

  1. stirringstirred at 25° C. for 30 min
  2. customThe resulting reaction mixture
  3. stirringwas stirred at 25° C. for 17 h
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. custompurified via Biotage chromatography (FLASH 40S, Silica, 1/1 hexanes/ethyl acetate)

출처 및 근거

ORD 기록
ord-7b36577fee8c45a5be0aa5f83c539d08
출처 데이터셋
uspto-grants-2003_08
특허 번호
US06610846B1

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