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

反応式

HRID 277331 の反応式
[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

参加物

7

反応物 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

生成物 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 Hydrochloride収率 55.6%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒HCID 8471Triethylamine溶媒

反応条件

温度
100 °C

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-014da15097e94485a00b85539a2990fb
出典データセット
uspto-grants-2002_03
特許番号
US06355798B1

関連ノート

読み込み中…