Hydrochloric Acid → 3-Butyl-4-[4-(4-chloro-benzyloxy)-phenyl]-6-(1-methyl-piperidin-4-yloxy)-pyridazine dihydrochloride

HRID 2168695노트

반응식

HRID 2168695 반응식
[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].[Cl:26][C:27]1[CH:34]=[CH:33][C:30]([CH2:31]Br)=[CH:29][CH:28]=1.C(=O)([O-])[O-].[K+].[K+].[ClH:41]>CN(C=O)C.O.CCOC(C)=O.C(Cl)Cl.CCOCC>[ClH:26].[ClH:41].[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][CH2:31][C:30]2[CH:33]=[CH:34][C:27]([Cl:26])=[CH:28][CH:29]=2)=[CH:15][CH:16]=1)[CH2:2][CH2:3][CH3:4]

참가 물질

9

반응물 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 1363862594-[3-Butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-phenol

생성물 1

HCID 673751643-Butyl-4-[4-(4-chloro-benzyloxy)-phenyl]-6-(1-methyl-piperidin-4-yloxy)-pyridazine dihydrochloride

시약·촉매·용매 4

HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매HCID 22728543Water ethylacetate용매

반응 조건

온도
80 °C

실험 절차

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 4-chlorobenzyl bromide (0.4 mmol, 83 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 (69 mg). LCMS: m/z 467 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.44-7.47 (2 H, m), 7.38-7.41 (2 H, m), 7.32-7.35 (2 H, m), 7.12-7.15 (2 H, m), 7.02 (1 H, s), 5.47-5.53 (1 H, m), 5.16 (2 H, s), 3.30-3.49 (4 H, m), 2.91 (3 H, s), 2.89-2.94 (2 H, m), 2.22-2.37 (4 H, m), 1.44-1.52 (2 H, m), 1.18-1.26 (2 H, m), 0.79 (3 H, t).

후처리

  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

출처 및 근거

ORD 기록
ord-ab1c4426bf63487b92b2d2a1c1093a16
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09045461B2

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