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

HRID 2365724노트

반응식

HRID 2365724 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][CH:17]=3)[C:12]2=[O:20])[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:21]([O:24][CH2:25][CH2:26][N:27]1[CH:31]=[CH:30][C:29]([NH2:32])=[N:28]1)(C)C.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][CH:17]=3)[C:12]2=[O:20])[C:8]([NH:32][C:29]2[CH:30]=[CH:31][N:27]([CH2:26][CH2:25][O:24][CH3:21])[N:28]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 61485333HCID 61485333, 화합물HCID 70945105(S)-3-Cyclopentyl-2-(1-oxoisoindolin-2-yl)propanoic acid

생성물 1

HCID 70674448(S)-3-cyclopentyl-N-[1-(2-methoxy-ethyl)-1H-pyrazol-3-yl]-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide수율 79.3%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of (S)-3-cyclopentyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (prepared as in Example 9, 94 mg, 0.35 mmol) and 1-(2-isopropoxy-ethyl)-1H-pyrazol-3-ylamine (prepared as in US 20080021032, Example 101, 70 mg, 0.41 mmol) and benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (Chemimpex, 0.18 g, 0.41 mmol) in methylene chloride (5 mL) was added N,N-diisopropylethylamine (0.18 mL, 1.0 mmol) dropwise and the resulting solution stirred at room temperature for 4 h. The solution was diluted with methylene chloride, washed with a 1 N hydrochloric acid solution (25 mL), a saturated sodium bicarbonate solution (25 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% ethyl acetate/hexane) to afford (S)-3-cyclopentyl-N-[1-(2-methoxy-ethyl)-1H-pyrazol-3-yl]-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide (110 mg, 75%) as an off white solid: [α]31D=−50.6°, (c=0.36, chloroform); HR-ES(+) m/e calcd for C24H32N4O3 [M+H]+ 425.2547, observed 425.2547; 1H NMR (300 MHz, DMSO-d6) δ ppm 0.77-2.18 (m, 17H), 3.40-5.25 (m, 8H), 6.39 (d, J=2.11 Hz, 1H), 7.26-7.91 (m, 5H), 10.86 (s, 1H).

후처리

  1. washwashed with a 1 N hydrochloric acid solution (25 mL)
  2. dry with materiala saturated sodium bicarbonate solution (25 mL) dried over magnesium sulfate
  3. filtrationThe mixture was filtered
  4. customevaporated
  5. customthe resulting material purified

출처 및 근거

ORD 기록
ord-24f42fbe61ac4c679842a53dae9577f5
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08697705B2

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