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

HRID 398702

反応式

HRID 398702 の反応式
[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]

参加物

8

反応物 4

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

生成物 1

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

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 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.

後処理

  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)

出典と根拠

ORDレコード
ord-0305b15bc69948febcc1489163f93965
出典データセット
uspto-grants-2003_08
特許番号
US06610846B1

関連ノート

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