2,6-Lutidine → (S)-3-cyclopentyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-N-(3-methyl-[1,2,4]thiadiazol-5-yl)-propionamide

HRID 18952ノート

反応式

HRID 18952 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.[NH2:25][C:26]1[S:30][N:29]=[C:28]([CH3:31])[N:27]=1.N1C(C)=CC=CC=1C>ClCCl.CN(C)C=O>[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:25][C:26]2[S:30][N:29]=[C:28]([CH3:31])[N:27]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

参加物

7

反応物 4

HCID 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 3506395-Amino-3-methyl-1,2,4-thiadiazoleHCID 66894643(S)-3-cyclopentyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionic acid

生成物 1

HCID 66895000(S)-3-cyclopentyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-N-(3-methyl-[1,2,4]thiadiazol-5-yl)-propionamide

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒2 回

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, 102 mg, 0.40 mmol) in dichloromethane (2 mL) was treated with oxalyl chloride (218 μL of 2M solution in dichloromethane), and N,N-dimethylformamide (1 drop). Effervescence was observed. The reaction mixture was stirred for 0.5 h at 25° C., under nitrogen. The reaction mixture was concentrated, and dissolved in N,N-dimethylformamide (2 mL) and treated with 5-amino-3-methyl-1,2,4-thiadiazole (48 mg, 0.41 mmol), and 2,6-lutidine (64 mg, 0.60 mmol). The reaction mixture was stirred at 25° C., under nitrogen for 18 h. The reaction mixture was diluted with methylene chloride, 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 35% methanol/dichloromethane) to afford ((S)-3-cyclopentyl-2-(4-methoxy-2-oxo-2,5-dihydro-pyrrol-1-yl)-N-(3-methyl-[1,2,4]thiadiazol-5-yl)-propionamide (30 mg, 22% as a white powder: LR-ES-MS m/z calculated for C16H22N4O3S [M]+ 350, observed [M+H]+ 351; 1H NMR (300 MHz, CDCl3) δ ppm 0.74-0.96 (m, 1H) 1.03-1.42 (m, 3H) 1.38-2.15 (m, 7H) 2.53 (s, 3H) 3.83 (s, 3H) 3.98 (d, J=17.8 Hz, 1H) 4.13 (d, J=17.8 Hz, 1H) 5.24 (t, J=7.7 Hz, 1H) 5.38 (s, 1H).

後処理

  1. concentrationThe reaction mixture was concentrated
  2. dissolutiondissolved in N,N-dimethylformamide (2 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 35% methanol/dichloromethane)

出典と根拠

ORDレコード
ord-e917acbdcbcd4a13bc929dce7c7d1806
出典データセット
uspto-grants-2010_06
特許番号
US07741327B2

反応ノート

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