Diisopropylethylamine → (S)-3-cyclopentyl-N-[1-(2-methoxy-ethyl)-1H-pyrazol-3-yl]-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionamide

HRID 1261492

반응식

HRID 1261492 반응식
[CH:1]1([CH2:6][C@H:7]([N:11]2[CH2:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[C:20]([F:23])([F:22])[F:21])[C:12]2=[O:24])[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:25][O:26][CH2:27][CH2:28][N:29]1[CH:33]=[CH:32][C:31]([NH2:34])=[N:30]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>C(Cl)Cl>[CH:1]1([CH2:6][C@H:7]([N:11]2[CH2:19][C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[C:20]([F:23])([F:22])[F:21])[C:12]2=[O:24])[C:8]([NH:34][C:31]2[CH:32]=[CH:33][N:29]([CH2:28][CH2:27][O:26][CH3:25])[N:30]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 451167281-(2-methoxyethyl)-1H-pyrazol-3-amineHCID 70945341(S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionic acid

생성물 1

HCID 70674452(S)-3-cyclopentyl-N-[1-(2-methoxy-ethyl)-1H-pyrazol-3-yl]-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionamide수율 43.1%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of (S)-3-cyclopentyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionic acid (prepared as in Example 1, 71 mg, 0.21 mmol) and 1-(2-methoxy-ethyl)-1H-pyrazol-3-ylamine (prepared as in US 20080021032, Example 72, 32 mg, 0.23 mmol) and benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (Chemimpex, 0.11 g, 0.25 mmol) in methylene chloride (5 mL) was added N,N-diisopropylethylamine (0.11 mL, 0.62 mmol) dropwise and the resulting solution stirred at room temperature over night. The solution was diluted with methylene chloride, washed with a 1 N hydrochloric acid solution (15 mL), a saturated sodium bicarbonate solution (20 mL) dried over magnesium sulfate. The mixture was filtered and evaporated and the resulting material purified via automated flash chromatography (Analogix, SF4-12 g column, 50-80% ethyl acetate/hexanes) to give (S)-3-cyclopentyl-N-[1-(2-methoxy-ethyl)-1H-pyrazol-3-yl]-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-propionamide (42 mg, 43%) as an off white solid: HR-ES(+) m/e calcd for C23H27N4O3F3 [M+H]+ 465.2108, observed 465.2107; 1H NMR (300 MHz, DMSO-d6) δ ppm 1.04-2.18 (m, 10H), 3.20 (s, 3H), 3.51-4.28 (m, 4H), 4.60-5.34 (m, 3H), 6.40 (d, J=1.81 Hz, 1H), 7.41-8.28 (m, 5H), 10.93 (s, 1H).

후처리

  1. washwashed with a 1 N hydrochloric acid solution (15 mL)
  2. dry with materiala saturated sodium bicarbonate solution (20 mL) dried over magnesium sulfate
  3. filtrationThe mixture was filtered
  4. customevaporated
  5. customthe resulting material purified

출처 및 근거

ORD 기록
ord-20fd8fd7f6e14997887422611e9e7c04
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08470866B2

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