Diisopropylethylamine → N-(6-methoxypyridin-3-yl)-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamide

HRID 1666335

반응식

HRID 1666335 반응식
Cl.[NH:2]1[CH2:7][CH2:6][C:5](=[CH:8][C:9]2[CH:10]=[C:11]([CH:23]=[CH:24][CH:25]=2)[O:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][N:14]=2)[CH2:4][CH2:3]1.[CH3:26][O:27][C:28]1[N:33]=[CH:32][C:31]([NH:34][C:35](=O)[O:36]C2C=CC=CC=2)=[CH:30][CH:29]=1.C(N(C(C)C)CC)(C)C>CS(C)=O>[CH3:26][O:27][C:28]1[N:33]=[CH:32][C:31]([NH:34][C:35]([N:2]2[CH2:7][CH2:6][C:5](=[CH:8][C:9]3[CH:25]=[CH:24][CH:23]=[C:11]([O:12][C:13]4[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:20])[F:21])=[CH:15][N:14]=4)[CH:10]=3)[CH2:4][CH2:3]2)=[O:36])=[CH:30][CH:29]=1

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 20185962Phenyl 6-methoxypyridin-3-ylcarbamateHCID 668761612-(3-(Piperidin-4-ylidenemethyl)phenoxy)-5-(trifluoromethyl)pyridine hydrochloride

생성물 1

HCID 24967994N-(6-methoxypyridin-3-yl)-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamide수율 58%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
50 °C

실험 절차

A solution of 2-(3-piperidin-4-ylidenemethyl-phenoxy)-5-trifluoromethyl-pyridine hydrochloride (0.371 g, 1.00 mmol) (from Example 1, Step 5) and phenyl 6-methoxypyridin-3-ylcarbamate (0.244 g, 1.00 mmol, from Step 1) in DMSO (2.5 mL) was treated with diisopropylethylamine (0.155 g, 1.2 mmol) and heated to 50° C. After 3 h, the reaction mixture was partitioned between water and ethyl acetate. The organic layer was separated and the aqueous layer was extracted again with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (10% of the 1N NH3 in MeOH, in dichloromethane) to afford the title compound (280 mg, 58%) as white crystals after trituration in diethyl ether. MS (APCI 10V) AP+ 485.30; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.34 (t, J=5.46 Hz, 2H) 2.46 (t, J=5.46 Hz, 2H) 3.46 (t, J=5.46 Hz, 2H) 3.54 (t, J=5.46 Hz, 2H) 3.76 (s, 3H) 6.38 (s, 1H) 6.69 (d, J=8.77 Hz, 1H) 7.03 (m, 2H) 7.12 (d, J=7.80 Hz, 1H) 7.21 (d, J=8.60 Hz, 1H) 7.4 (dd, J=8.5 Hz, 1 Hz, 1H) 7.73 (dd, J=8.9 Hz, 2.7 Hz, 1H) 8.14 (d, J=2.5 Hz, 1H) 8.20 (dd, J=8.77 Hz, 2.5 Hz, 1H) 8.49 (s, 1H) 8.55 (d, J=2.5 Hz, 1H).

후처리

  1. customthe reaction mixture was partitioned between water and ethyl acetate
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted again with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (10% of the 1N NH3 in MeOH

출처 및 근거

ORD 기록
ord-e17c6628834d45ef8c154c153e1a472b
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08044052B2

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