Hydrochloric Acid → 3-Butyl-6-(1-methyl-piperidin-4-yloxy)-4-[4-(pyridazin-3-ylmethoxy)-phenyl]-pyridazine trihydrochloride

HRID 1971974ノート

反応式

HRID 1971974 の反応式
[CH2:1]([C:5]1[N:6]=[N:7][C:8]([O:18][CH:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)=[CH:9][C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)[CH2:2][CH2:3][CH3:4].Br[CH2:27][C:28]1[N:29]=[N:30][CH:31]=[CH:32][CH:33]=1.C(=O)([O-])[O-].[K+].[K+].[ClH:40]>CN(C=O)C.O.CCOC(C)=O.C(Cl)Cl.CCOCC>[ClH:40].[ClH:40].[ClH:40].[CH2:1]([C:5]1[N:6]=[N:7][C:8]([O:18][CH:19]2[CH2:20][CH2:21][N:22]([CH3:25])[CH2:23][CH2:24]2)=[CH:9][C:10]=1[C:11]1[CH:12]=[CH:13][C:14]([O:17][CH2:27][C:28]2[N:29]=[N:30][CH:31]=[CH:32][CH:33]=2)=[CH:15][CH:16]=1)[CH2:2][CH2:3][CH3:4]

参加物

9

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 215352003-(Bromomethyl)pyridazineHCID 1363862594-[3-Butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-phenol

生成物 1

HCID 673750633-Butyl-6-(1-methyl-piperidin-4-yloxy)-4-[4-(pyridazin-3-ylmethoxy)-phenyl]-pyridazine trihydrochloride

試薬・触媒・溶媒 4

HCID 3283Diethyl Ether溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 22728543Water ethylacetate溶媒

反応条件

温度
80 °C

実験手順

To a solution of 4-[3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-phenol (Example 19) (0.2 mmol, 69 mg) in dry DMF (1 mL) was added 3-bromomethyl-pyridazine (0.4 mmol, 70 mg), and potassium carbonate (0.4 mmol, 56 mg). And the mixture was stirred at 80° C. over night. It was then diluted with water/EtOAc. The organic layers were combined, dried, and condensed in vacuo and the residue was purified by silica gel chromatography (DCM to DCM+10% MeOH) to give a colorless sticky solid, which was dissolved in DCM (1.0 mL), 1N HCl in ether (1.0 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (77 mg). LCMS: m/z 435 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.81 and 7.88 (1H, s), 7.46-7.51 (2H, m), 7.30-7.41 (3H, m), 7.20-7.25 (2H, m), 5.37-5.53 (1H, m), 5.20 (2H, s), 3.30-3.53 (4H, m), 3.12-3.17 (2H, m), 2.93 (3H, s), 2.08-2.58 (4H, m), 1.44-1.53 (2H, m), 1.24-1.34 (2H, m), 0.81 (3H, t).

後処理

  1. customdried
  2. customcondensed in vacuo
  3. customthe residue was purified by silica gel chromatography (DCM to DCM+10% MeOH)
  4. customto give a colorless sticky solid, which
  5. customcondensed
  6. customtriturated with hexanes

出典と根拠

ORDレコード
ord-e5d376be6c0b470ca8690ca22f1db19b
出典データセット
uspto-grants-2013_04
特許番号
US08431575B2

反応ノート

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