Pyridine → 3-(5-((4-(1-(4-(2,3-Dimethylphenoxy)butanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)-1H-pyrazol-1-yl)methyl)-1H-tetrazol-1-yl)propanenitrile

HRID 2175275노트

반응식

HRID 2175275 반응식
[C:1]([CH2:3][CH2:4][NH:5][C:6](=O)[CH2:7][N:8]1[CH:12]=[C:11]([C:13]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:14]=2[CH2:15][CH2:16][CH2:17][N:18]3[C:23](=[O:36])[CH2:24][CH2:25][CH2:26][O:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([CH3:34])[C:29]=2[CH3:35])[CH:10]=[N:9]1)#[N:2].N1C=CC=CC=1.P(Cl)(Cl)(Cl)(Cl)Cl.C[Si]([N:54]=[N+:55]=[N-:56])(C)C>C(Cl)Cl>[CH3:35][C:29]1[C:30]([CH3:34])=[CH:31][CH:32]=[CH:33][C:28]=1[O:27][CH2:26][CH2:25][CH2:24][C:23]([N:18]1[C:19]2[C:14](=[C:13]([C:11]3[CH:10]=[N:9][N:8]([CH2:7][C:6]4[N:5]([CH2:4][CH2:3][C:1]#[N:2])[N:56]=[N:55][N:54]=4)[CH:12]=3)[CH:22]=[CH:21][CH:20]=2)[CH2:15][CH2:16][CH2:17]1)=[O:36]

참가 물질

6

반응물 4

HCID 1049PyridineHCID 24819Phosphorus pentachlorideHCID 78378AzidotrimethylsilaneHCID 70983502N-(2-cyanoethyl)-2-(4-(1-(4-(2,3-dimethylphenoxy)butanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)-1H-pyrazol-1-yl)acetamide

생성물 1

HCID 709827333-(5-((4-(1-(4-(2,3-Dimethylphenoxy)butanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)-1H-pyrazol-1-yl)methyl)-1H-tetrazol-1-yl)propanenitrile수율 81%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of N-(2-cyanoethyl)-2-(4-(1-(4-(2,3-dimethylphenoxy)butanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)-1H-pyrazol-1-yl)acetamide (20 mg, 0.04 mmol) and pyridine (19 μL, 0.24 mmol) in DCM (0.4 mL) under argon was added PCl5 (13 mg, 0.06 mmol) in one portion, and the resulting mixture was heated to reflux for 3 h. The reaction was cooled to room temperature and trimethylsilyl azide (18 mg, 0.16 mmol) was added. The resulting mixture was stirred at room temperature overnight and carefully quenched with saturated aqueous NaHCO3. The resulting mixture was stirred vigorously for 15 min. The organic phase was separated, dried over anhydrous Na2SO4, filtered, and concentrated. The resulting residue was purified by flash chromatography (0-100% ethyl acetate:hexanes) to afford the title compound (17 mg, 81% yield) as white foam. LCMS, [M+H]+=525.2. 1H NMR (400 MHz, CDCl3) δ 7.54 (s, 1H), 7.47 (s, 1H), 7.30-7.16 (m, 2H), 7.10 (d, J=8.7 Hz, 1H), 7.03 (t, J=7.9 Hz, 1H), 6.76 (d, J=7.5 Hz, 1H), 6.64 (d, J=8.2 Hz, 1H), 5.74 (s, 2H), 4.95 (t, J=6.9 Hz, 2H), 3.93 (s, 2H), 3.78 (t, J=6.8 Hz, 2H), 3.06 (t, J=6.9 Hz, 2H), 2.74 (t, J=7.1 Hz, 2H), 2.52 (s, 2H), 2.24-2.11 (m, 5H), 1.96-1.78 (m, 5H).

후처리

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux for 3 h
  3. customcarefully quenched with saturated aqueous NaHCO3
  4. stirringThe resulting mixture was stirred vigorously for 15 min
  5. customThe organic phase was separated
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was purified by flash chromatography (0-100% ethyl acetate:hexanes)

출처 및 근거

ORD 기록
ord-7b71fa9cc3f2427b8873f0999c3edd4d
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09062028B2

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