Diisopropylethylamine → (S)-3-cyclopentyl-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 18965

반응식

HRID 18965 반응식
[CH:1]1([CH2:6][C@H:7]([N:16]2[CH2:20][C:19]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[O:28][CH3:29])=[CH:18][C:17]2=[O:30])[C:8]([NH:10][C:11]2SC=C[N:15]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.NC1[CH:36]=[CH:35][N:34]([CH2:37][C:38]([CH3:41])([OH:40])[CH3:39])N=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>ClCCl>[CH:1]1([CH2:6][C@H:7]([N:16]2[CH2:20][C:19]([O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[O:28][CH3:29])=[CH:18][C:17]2=[O:30])[C:8]([NH:10][C:11]2[CH:36]=[CH:35][N:34]([CH2:37][C:38]([OH:40])([CH3:41])[CH3:39])[N:15]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 44253481HCID 44253481, 화합물HCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-ol

생성물 1

HCID 44253483(S)-3-cyclopentyl-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 22.6%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

반응 조건

온도
25 °C

실험 절차

A solution of (S)-3-cyclopentyl-2-[4-(2-methoxy-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl)-propionic acid (prepared as in Example 26, 150 mg, 0.43 mmol) in dichloromethane (10 mL) was treated with 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 75 mg, 0.48 mmol), benzotriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (230 mg, 0.52 mmol) and N,N-diisopropylethylamine (170 mg, 1.30 mmol). The reaction mixture was 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, 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 12 g; 0% to 100% ethyl acetate/hexanes) to afford (S)-3-cyclopentyl-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 (47 mg, 22%) as a white solid: LR-ES-MS m/z calculated for C26H34N4O5 [M]+ 482, observed [M+H]+ 483; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.00-1.94 (m, 11H) 1.04 (br. s., 3H) 1.06 (br. s., 3H) 3.81 (s, 3H) 3.89 (s, 2H) 4.13 (d, J=18.4 Hz, 1H) 4.52 (d, J=18.4 Hz, 1H) 4.68 (s, 1H) 4.70 (s, 1H) 4.81 (dd, J=10.4, 4.7 Hz, 1H) 6.44 (d, J=2.2 Hz, 1H) 6.95-7.05 (m, 1H) 7.18-7.24 (m, 1H) 7.25-7.36 (m, 2H) 7.53 (d, J=2.2 Hz, 1H) 10.79 (s, 1H).

후처리

  1. washwashed with 2N aqueous hydrochloric acid, saturated sodium bicarbonate solution, saturated sodium chloride solution
  2. customdried
  3. concentrationThe organic layer was concentrated
  4. 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-6b518339d56e46b5ba50bd8ab1ce2003
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07741327B2

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