Triethylamine → 4-(3-(5-methylpyridin-2-yloxy)benzylidene)-N-(pyridazin-3-yl)piperidine-1-carboxamide

HRID 1666407노트

반응식

HRID 1666407 반응식
Cl.[CH3:2][C:3]1[CH:4]=[CH:5][C:6]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([CH:16]=[C:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[CH:11]=2)=[N:7][CH:8]=1.[N:23]1[CH:28]=[CH:27][CH:26]=[C:25]([NH:29][C:30](=O)[O:31]C2C=CC=CC=2)[N:24]=1.C(N(CC)CC)C>C(#N)C>[CH3:2][C:3]1[CH:4]=[CH:5][C:6]([O:9][C:10]2[CH:11]=[C:12]([CH:13]=[CH:14][CH:15]=2)[CH:16]=[C:17]2[CH2:22][CH2:21][N:20]([C:30]([NH:29][C:25]3[N:24]=[N:23][CH:28]=[CH:27][CH:26]=3)=[O:31])[CH2:19][CH2:18]2)=[N:7][CH:8]=1

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 20150036Phenyl pyridazin-3-ylcarbamateHCID 668761665-Methyl-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine hydrochloride

생성물 1

HCID 249644264-(3-(5-methylpyridin-2-yloxy)benzylidene)-N-(pyridazin-3-yl)piperidine-1-carboxamide수율 81.9%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

5-Methyl-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine hydrochloride (507 mg, 1.6 mmol, from Example 44, Step 5), phenyl pyridazin-3-ylcarbamate (430 mg, 2.0 mmol) and triethylamine (0.892 mL, 6.4 mmol) were combined in acetonitrile (10 mL) and stirred at room temperature. After 16 h, the reaction was concentrated and the residue was partitioned between EtOAc and water. The organic layer was separated, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (0-10%, MeOH:CH2Cl2) to afford the title compound (526 mg) as a foamy white solid. MS APCI M+ 402.1, 281.2 M− 400.1; 1H NMR (400 MHz, CD3OD) δ ppm 2.29 (s, 3H) 2.46 (td, J=5.71, 0.93 Hz, 2H) 2.58 (td, J=5.74, 1.06 Hz, 2H) 3.52-3.61 (m, 2H) 3.65-3.71 (m, 2H) 6.44 (s, 1H) 6.85 (dd, J=8.41, 0.33 Hz, 1H) 6.89-6.96 (m, J=4.21, 4.21, 2.47, 1.01 Hz, 2H) 7.04-7.11 (m, J=7.63, 1.41, 1.04, 0.83 Hz, 1H) 7.31-7.42 (m, 1H) 7.59 (dd, J=9.09, 4.70 Hz, 1H) 7.66 (ddd, J=8.39, 2.49, 0.66 Hz, 1H) 7.97 (td, J=1.63, 0.77 Hz, 1H) 8.12 (d, J=9.32 Hz, 1H) 8.79 (d, J=4.37 Hz, 1H).

후처리

  1. concentrationthe reaction was concentrated
  2. customthe residue was partitioned between EtOAc and water
  3. customThe organic layer was separated
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography (0-10%, MeOH:CH2Cl2)

출처 및 근거

ORD 기록
ord-8558b4454d90476ab418e75e7f0d9982
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08044052B2

반응 노트

불러오는 중…