Diisopropylethylamine → (S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone

HRID 1423156노트

반응식

HRID 1423156 반응식
[CH2:1]([C@@H:8]1[NH:13][CH2:12][CH2:11][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:28][C:29]1[NH:33][N:32]=[C:31]([CH2:34][C:35](O)=[O:36])[N:30]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CN(C=O)C>[CH2:1]([C@H:8]1[CH2:9][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:11][CH2:12][N:13]1[C:35](=[O:36])[CH2:34][C:31]1[N:30]=[C:29]([CH3:28])[NH:33][N:32]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 70194772-(3-methyl-1H-1,2,4-triazol-5-yl)acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 16725642(S)-3-Benzyl-1-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine2회

생성물 1

HCID 58189118(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-(5-methyl-1H-1,2,4-triazol-3-yl)ethanone수율 65%

시약·촉매·용매 1

HCID 22350042dichloromethane N,N-dimethylformamide용매

실험 절차

A solution of 3-benzyl-1-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine (Example 2, Compound 90) (100 mg, 0.273 mmol), in CH2Cl2:DMF (1:1, 3 mL), then treated with (5-methyl-1H[1,2,4]triazol-3-yl)-acetic acid (50.0 mg, 0.355 mmol), followed by the addition of diisopropylethylamine μL, 0.819 mmol) and HATU (135 mg, 0.355 mmol). (100 The reaction stirred at room temperature for 8 h. The solution was washed with a saturated aqueous solution of NaHCO3 (10 mL) followed by brine (10 mL). The organic portion was dried over MgSO4, filtered and evaporated to an oil which was purified by silica gel flash chromatography with 5% then 10% MeOH/EtOAc as eluant to afford product as a colorless solid (86 mg, 65%). 1H NMR (CDCl3) 1.50-1.65 (m, 4H), 1.70-2.00 (m, 6H), 2.42 (s, 3H), 2.46 (s, 2H), 2.61-2.99 (m, 2H), 3.21-3.51 (m, 3H), 3.72-3.99 (m, 4H), 4.62-4.79 (m, 1H), 6.38-6.60 (m, 2H), 6.70-6.82 (m, 1H), 7.20-7.39 (m, 5H). 13C NMR 44.8 (CH2), 53.5 (CH2), 54.8 (CH), 55.3 (CH2), 56.6 (CH2), 63.2 (CH2), 105.4 (CH), 127.1 (CH), 128.2 (CH), 129.0 (CH), 130.0 (CH), 138.0, 139.8 (CH). LC/MS (Method B) 3.32 min, [M+1]+ 490.2.

후처리

  1. washThe solution was washed with a saturated aqueous solution of NaHCO3 (10 mL)
  2. dry with materialThe organic portion was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated to an oil which
  5. customwas purified by silica gel flash chromatography with 5%

출처 및 근거

ORD 기록
ord-c138d17521d7454f9677317c6df9945f
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08927546B2

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