1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (S)-3-cyclohexyl-N-(1-methyl-1H-pyrazol-3-yl)-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionamide

HRID 18967

반응식

HRID 18967 반응식
[CH:1]1([CH2:7][C@H:8]([N:22]2[CH2:26][C:25]([O:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[O:34][CH3:35])=[CH:24][C:23]2=[O:36])[C:9]([NH:11][C:12]2[CH:16]=[CH:15][N:14]([CH2:17]C(O)(C)C)[N:13]=2)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.CN1C=CC(N)=N1>ClCCl>[CH:1]1([CH2:7][C@H:8]([N:22]2[CH2:26][C:25]([O:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[O:34][CH3:35])=[CH:24][C:23]2=[O:36])[C:9]([NH:11][C:12]2[CH:16]=[CH:15][N:14]([CH3:17])[N:13]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

참가 물질

6

반응물 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 1372541-Methyl-3-aminopyrazoleHCID 44253482(S)-3-cyclohexyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionamide

생성물 1

HCID 44253480(S)-3-cyclohexyl-N-(1-methyl-1H-pyrazol-3-yl)-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionamide수율 33%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

반응 조건

온도
25 °C

실험 절차

A solution of (S)-3-cyclohexyl-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionic acid (prepared as in Example 28, 200 mg, 0.56 mmol) in dichloromethane (10 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (87 mg, 0.56 mmol) and 1-hydroxybenzotriazole (80 mg, 0.58 mmol). The reaction mixture was stirred at 25° C. for 2 h followed by the addition of 1-methyl-1H-pyrazol-3-amine (60 mg, 0.61 mmol). The reaction mixture was then stirred for 18 h at 25° C., under nitrogen. The reaction mixture was diluted with dichloromethane, washed with 2N aqueous hydrochloric acid, saturated sodium bicarbonate solution, a saturated sodium chloride solution and dried over magnesium sulfate. The organic layer was concentrated, and the crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g; 0% to 100% ethyl acetate/hexanes) to afford (S)-3-cyclohexyl-N-(1-methyl-1H-pyrazol-3-yl)-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionamide (80 mg, 33%) as a light yellow solid: LR-ES-MS m/z calculated for C24H30N4O4 [M]+ 438, observed [M+H]+ 439; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.78-1.28 (m, 6H) 1.44-1.86 (m, 7H) 3.73 (s, 3H) 3.81 (s, 3H) 4.10 (d, J=18.2 Hz, 1H) 4.49 (d, J=18.2 Hz, 1H) 4.71 (s, 1H) 4.89 (dd, J=10.6, 5.1 Hz, 1H) 6.39 (d, J=2.1 Hz, 1H) 6.95-7.06 (m, 1H) 7.21 (d, J=7.5 Hz, 1H) 7.25-7.36 (m, 2H) 7.54 (d, J=2.1 Hz, 1H) 10.70 (s, 1H).

후처리

  1. stirringThe reaction mixture was then stirred for 18 h at 25° C., under nitrogen
  2. washwashed with 2N aqueous hydrochloric acid, saturated sodium bicarbonate solution
  3. dry with materiala saturated sodium chloride solution and dried over magnesium sulfate
  4. concentrationThe organic layer was concentrated
  5. customthe crude product was purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 12 g; 0% to 100% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-bcc1c1964b8c492286a42481709593c3
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741327B2

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