Oxalyl chloride → (S)-3-cyclopentyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-N-pyrazin-2-yl-propionamide

HRID 18956

反応式

HRID 18956 の反応式
[CH:1]1([CH2:6][C@H:7]([N:11]2[CH2:15][C:14]([O:16][CH3:17])=[CH:13][C:12]2=[O:18])[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[N:25]1[CH:30]=[CH:29][N:28]=[CH:27][C:26]=1[NH2:31].C(N(CC)C(C)C)(C)C>C1C=CC=CC=1.CN(C)C=O.ClCCl>[CH:1]1([CH2:6][C@H:7]([N:11]2[CH2:15][C:14]([O:16][CH3:17])=[CH:13][C:12]2=[O:18])[C:8]([NH:31][C:26]2[CH:27]=[N:28][CH:29]=[CH:30][N:25]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

参加物

8

反応物 4

HCID 65578Oxalyl chlorideHCID 78747AminopyrazineHCID 81531DiisopropylethylamineHCID 66894643(S)-3-cyclopentyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionic acid

生成物 1

HCID 44253056(S)-3-cyclopentyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-N-pyrazin-2-yl-propionamide収率 3.7%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide触媒HCID 241Benzene溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
25 °C

実験手順

A solution of (S)-3-cyclopentyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionic acid (prepared as in Example 1, 106 mg, 0.41 mmol) in benzene (10 mL) was treated with oxalyl chloride (55 mg, 0.43 mmol), and N,N-dimethylformamide (1 drop). Effervescence was observed. The reaction mixture was stirred for 2 h at 25° C., under nitrogen. The reaction mixture was concentrated, and dissolved in dichloromethane (10 mL) and treated with pyrazin-2-ylamine (42 mg, 0.43 mmol), and N,N-diisopropylethylamine (161 mg, 1.23 mmol). The reaction mixture was stirred at 25° C., under nitrogen for 18 h. The reaction mixture was diluted with dichloromethane, washed with 2N aqueous hydrochloric acid, saturated sodium chloride solution and dried. The organic layer was concentrated, and the crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 4 g; 0% to 10% methanol/dichloromethane) to afford (S)-3-cyclopentyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-N-pyrazin-2-yl-propionamide (5 mg, 3%) as a white solid: LR-ES-MS m/z calculated for C17H22N4O3 [M]+ 330, observed [M+H]+ 331; 1H NMR (400 MHz, CDCl3) δ ppm 1.13-1.23 (m, 2H) 1.48-1.98 (m, 8H) 1.98-2.09 (m, 1H) 3.82 (s, 3H) 3.94 (d, J=17.5 Hz, 1H) 4.03 (d, J=17.5 Hz, 1H) 4.83 (dd, J=9.1, 6.5 Hz, 1H) 5.15 (s, 1H) 8.28 (dd, J=2.6, 1.5 Hz, 1H) 8.33 (d, J=2.6 Hz, 1H) 9.09 (s, 1H) 9.47 (d, J=1.5 Hz, 1H).

後処理

  1. concentrationThe reaction mixture was concentrated
  2. dissolutiondissolved in dichloromethane (10 mL)
  3. stirringThe reaction mixture was stirred at 25° C., under nitrogen for 18 h
  4. washwashed with 2N aqueous hydrochloric acid, saturated sodium chloride solution
  5. customdried
  6. concentrationThe organic layer was concentrated
  7. customthe crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 4 g; 0% to 10% methanol/dichloromethane)

出典と根拠

ORDレコード
ord-29abd0e6fe244451bdfbfb51f1437968
出典データセット
uspto-grants-2010_06
特許番号
US07741327B2

関連ノート

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