6-Chloro-7-cyclobutyl-3-phenyl-1,2,4-triazolo[4,3-b]pyridazine → N-(7-Cyclobutyl-3-phenyl-1,2,4-triazolo[4,3-b]pyridazin-6-yl)-N-methyl-N-(1-methyl-1H-1,2,4-triazol-3-ylmethyl)amine Hydrochloride

HRID 277331

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HRID 277331 반응식
[Cl:1][C:2]1[C:3]([CH:17]2[CH2:20][CH2:19][CH2:18]2)=[CH:4][C:5]2[N:6]([C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[N:9][N:10]=2)[N:7]=1.[CH3:21][NH:22][CH2:23][C:24]1[N:28]=[CH:27][N:26]([CH3:29])[N:25]=1>C(N(CC)CC)C.CN(C=O)C.CO>[ClH:1].[ClH:1].[CH:17]1([C:3]2[C:2]([N:22]([CH3:21])[CH2:23][C:24]3[N:28]=[CH:27][N:26]([CH3:29])[N:25]=3)=[N:7][N:6]3[C:8]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=4)=[N:9][N:10]=[C:5]3[CH:4]=2)[CH2:20][CH2:19][CH2:18]1

참가 물질

7

반응물 2

HCID 110005936-Chloro-7-cyclobutyl-3-phenyl-1,2,4-triazolo[4,3-b]pyridazineHCID 18361748N,1-dimethyl-1H-1,2,4-Triazole-3-methanamine

생성물 2

HCID 313Hydrochloric AcidHCID 18314515N-(7-Cyclobutyl-3-phenyl-1,2,4-triazolo[4,3-b]pyridazin-6-yl)-N-methyl-N-(1-methyl-1H-1,2,4-triazol-3-ylmethyl)amine Hydrochloride수율 55.6%

시약·촉매·용매 3

HCID 887Methanol용매HCID 6228Dimethylformamide용매HCID 8471Triethylamine용매

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온도
100 °C

실험 절차

A mixture of 6-chloro-7-cyclobutyl-3-phenyl-1,2,4-triazolo[4,3-b]pyridazine (100 mg, 0.35 mmol) and N-methyl-N-(1-methyl-1H-1,2,4-triazol-3-ylmethyl)amine (150 mg, 1.2 mmol) in triethylamine (1 ml) and dry DMF (1 ml) was stirred and heated at 100° C. in a sealed tube for 16 hours. Upon cooling the volatiles were removed in vacuo, and the residue was partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate. The aqueous was further extracted with dichloromethane (x2). The combined extracts were dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with 2%→5% methanol-dichloromethane to give the free base as on oil. Treatment with a solution of hydrogen chloride in methanol gave the title compound (40 mg, 30%) as a pale yellow solid. 1H NMR (360 MHz, d6-DMSO) δ 1.86-1.92 (1H, m), 1.96-2.04 (1H, m), 2.20-2.32 (2H, m), 2.40-2.46 (2H, m), 2.97 (3H, s), 3.83 (3H, s), 4.42 (2H, s), 7.54-7.60 (3H, m), 8.26 (1H, s), 8.36 (2H, br d, J=8 Hz), 8.48 (1H, s); MS (ES+) m/e 374 [MH]+.

후처리

  1. temperatureUpon cooling the volatiles
  2. customwere removed in vacuo
  3. customthe residue was partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate
  4. extractionThe aqueous was further extracted with dichloromethane (x2)
  5. dry with materialThe combined extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by chromatography on silica gel
  9. washeluting with 2%→5% methanol-dichloromethane
  10. customto give the free base as on oil

출처 및 근거

ORD 기록
ord-014da15097e94485a00b85539a2990fb
출처 데이터셋
uspto-grants-2002_03
특허 번호
US06355798B1

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