Hydrochloric Acid → HCID 67371415、化合物

HRID 401906ノート

反応式

HRID 401906 の反応式
[ClH:1].Cl.[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:26][CH:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[CH:11][C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[CH:15][CH:14]=1)[CH2:4][CH2:5][CH3:6].[CH3:33][O:34][CH2:35][CH2:36]Br.C(=O)([O-])[O-].[K+].[K+].Cl>CCO.C(Cl)Cl.CCOCC>[ClH:1].[ClH:1].[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:26][CH:27]2[CH2:32][CH2:31][N:30]([CH2:36][CH2:35][O:34][CH3:33])[CH2:29][CH2:28]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[CH:17][CH:18]=1)[CH2:4][CH2:5][CH3:6]

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 809722-Bromoethyl methyl etherHCID 67375293HCID 67375293、化合物

生成物 1

HCID 67371415HCID 67371415、化合物収率 96.2%

試薬・触媒・溶媒 3

HCID 702Ethanol溶媒HCID 3283Diethyl Ether溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
60 °C

実験手順

To a solution of 3-butyl-4-(4-cyclohexyloxy-phenyl)-6-(piperidin-4-yloxy)-pyridazine dihydrochloride (Example 14, 0.2 mmol, 97 mg) in EtOH (2 mL) was added 2-bromoethyl methyl ether (0.6 mmol, 57 μL), and potassium carbonate (0.6 mmol, 83 mg). The mixture was stirred at 60° C. for 3 hours, then cooled to room temperature, and filtered through celite. The celite cake was washed with DCM. The organic layers were combined and condensed in vacuo, and the residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 in MeOH) to give a colorless sticky solid, which was dissolved in DCM (2 mL), 1N HCl in ether (2 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (52 mg). LCMS: m/z 469 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.31-7.40 (3H, m), 7.06-7.10 (2H, m), 5.38-5.57 (1H, m), 4.39-4.44 (1H, m), 3.53-3.78 (4H, m), 3.43 (3H, s), 3.25-3.42 (4H, m), 2.96-3.02 (2H, m), 2.04-2.55 (4H, m), 1.97-2.02 (2H, m), 1.78-1.83 (2H, m), 1.29-1.62 (8H, m), 1.22-1.30 (2H, m), 0.80 (3H, t).

後処理

  1. temperaturecooled to room temperature
  2. filtrationfiltered through celite
  3. washThe celite cake was washed with DCM
  4. customcondensed in vacuo
  5. customthe residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 in MeOH)
  6. customto give a colorless sticky solid, which
  7. waitkept at room temperature for 10 min
  8. customcondensed
  9. customtriturated with hexanes

出典と根拠

ORDレコード
ord-ad42d9d75f1844e7989f081ba9722c97
出典データセット
uspto-grants-2014_06
特許番号
US08741900B2

反応ノート

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