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

반응식

HRID 18952 반응식
[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

참가 물질

7

반응물 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

생성물 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

시약·촉매·용매 2

HCID 6228Dimethylformamide촉매HCID 6344Dichloromethane용매2회

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온도
25 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-e917acbdcbcd4a13bc929dce7c7d1806
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741327B2

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