1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (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

HRID 18966

반응식

HRID 18966 반응식
[CH:1]1([CH2:7][C@H:8]([N:12]2[CH2:16][C:15]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[O:24][CH3:25])=[CH:14][C:13]2=[O:26])[C:9](O)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[NH2:48][C:49]1[CH:53]=[CH:52][N:51]([CH2:54][C:55]([CH3:58])([OH:57])[CH3:56])[N:50]=1>ClCCl>[CH:1]1([CH2:7][C@H:8]([N:12]2[CH2:16][C:15]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[O:24][CH3:25])=[CH:14][C:13]2=[O:26])[C:9]([NH:48][C:49]2[CH:53]=[CH:52][N:51]([CH2:54][C:55]([OH:57])([CH3:56])[CH3:58])[N:50]=2)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

참가 물질

6

반응물 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-olHCID 66893870(S)-3-cyclohexyl-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionic acid

생성물 1

HCID 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)-propionamide수율 40%

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 (375 mg, 1.04 mmol) in dichloromethane (15 mL) was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (164 mg, 1.06 mmol) and 1-hydroxybenzotriazole (150 mg, 2.00 mmol). The reaction mixture was stirred at 25° C. for 2 h followed by the addition of 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 178 mg, 1.15 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-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionamide (200 mg, 40%) as an off-white solid: LR-ES-MS m/z calculated for C27H36N4O5 [M]+ 496, observed [M+H]+ 497; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.69-1.35 (m, 6H) 1.05 (br. s., 3H) 1.06 (br. s, 3H) 1.49-1.89 (m, 7H) 3.81 (s, 3H) 3.89 (s, 2H) 4.10 (d, J=18.4 Hz, 1H) 4.52 (d, J=18.4 Hz, 1H) 4.68 (s, 1H) 4.71 (s, 1H) 4.82-4.96 (m, 1H) 6.44 (d, J=2.2 Hz, 1H) 6.94-7.07 (m, 1H) 7.18-7.24 (m, 1H) 7.30 (m, 2H) 7.54 (d, J=2.2 Hz, 1H) 10.77 (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-429e4c4610c34629b002608dd9db3cf7
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741327B2

연결된 노트

불러오는 중…