Triethylamine → 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(2-methyl-pyrimidin-4-yl)-propionamide

HRID 398702

반응식

HRID 398702 반응식
[C:1]([C:3]1[CH:4]=[C:5]([CH:13]([CH2:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[C:14]([OH:16])=O)[CH:6]=[CH:7][C:8]=1[S:9]([CH3:12])(=[O:11])=[O:10])#[N:2].C(Cl)(=O)C(Cl)=O.[NH2:29][C:30]1[CH:35]=[CH:34][N:33]=[C:32]([CH3:36])[N:31]=1.C(N(CC)CC)C>C(Cl)Cl.CN(C)C=O>[C:1]([C:3]1[CH:4]=[C:5]([CH:13]([CH2:17][CH:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)[C:14]([NH:29][C:30]2[CH:35]=[CH:34][N:33]=[C:32]([CH3:36])[N:31]=2)=[O:16])[CH:6]=[CH:7][C:8]=1[S:9]([CH3:12])(=[O:11])=[O:10])#[N:2]

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 2957632-Methylpyrimidin-4-amineHCID 120694992-(3-Cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid

생성물 1

HCID 223151662-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(2-methyl-pyrimidin-4-yl)-propionamide수율 6%

시약·촉매·용매 3

HCID 6228Dimethylformamide촉매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

반응 조건

온도
0 °C

실험 절차

A solution of 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 75, 200 mg, 0.622 mmol) in methylene chloride (5 mL) was treated with N,N-dimethylformamide (2 drops) and then cooled to 0° C. The reaction mixture was then treated with oxalyl chloride (0.081 mL, 0.933 mmol). The resulting reaction mixture was allowed to warm to 25° C. where it was stirred for 1 h. The reaction mixture was then concentrated in vacuo. The resulting yellow gel was diluted with methylene chloride (2 mL) and then slowly added to a mixture of 4-amino-2-methylpyrimidine (102 mg, 0.933 mmol) and triethylamine (0.173 mL, 1.24 mmol) in N,N-dimethylformamide (3 mL). The resulting reaction mixture was stirred at 25° C. for 24 h. The crude reaction mixture was directly purified by Biotage chromatography (FLASH 40S, Silica, 19/1 methylene chloride/methanol) to afford 2-(3-cyano-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(2-methyl-pyrimidin-4-yl)-propionamide (15 mg, 6%) as a white foam: mp 89-94° C. (foam to gel); EI-HRMS m/e calcd for C21H24N4O3S (M+) 412.1569, found 412.1568.

후처리

  1. customThe resulting reaction mixture
  2. temperatureto warm to 25° C. where it
  3. concentrationThe reaction mixture was then concentrated in vacuo
  4. additionThe resulting yellow gel was diluted with methylene chloride (2 mL)
  5. customThe resulting reaction mixture
  6. stirringwas stirred at 25° C. for 24 h
  7. customThe crude reaction mixture
  8. customwas directly purified by Biotage chromatography (FLASH 40S, Silica, 19/1 methylene chloride/methanol)

출처 및 근거

ORD 기록
ord-0305b15bc69948febcc1489163f93965
출처 데이터셋
uspto-grants-2003_08
특허 번호
US06610846B1

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