Cyclopropylacetylene → 3-Methyl-6-((6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)quinazolin-4(3H)-one

HRID 219266ノート

反応式

HRID 219266 の反応式
C1([C:4]2[O:8]N=[C:6]([C:9]3[CH:10]=[CH:11][C:12]4[N:13]([C:15](CN)=[N:16]N=4)N=3)[CH:5]=2)CC1.Cl/[C:21](=N\O)/[C:22]1[CH:23]=[CH:24][C:25]2[N:26]([C:28]([CH2:31]NC(=O)OC(C)(C)C)=[N:29][N:30]=2)[N:27]=1.[C:42]([CH:44]1[CH2:46][CH2:45]1)#[CH:43].[C:47](=O)([O-])O.[K+]>CCOC(C)=O>[CH3:47][N:16]1[C:4](=[O:8])[C:5]2[C:12](=[CH:11][CH:10]=[C:9]([CH2:31][C:28]3[N:26]4[N:27]=[C:22]([C:21]5[CH:46]=[CH:45][CH:44]=[CH:42][CH:43]=5)[CH:23]=[CH:24][C:25]4=[N:30][N:29]=3)[CH:6]=2)[N:13]=[CH:15]1

参加物

6

反応物 4

HCID 138823CyclopropylacetyleneHCID 516893Potassium BicarbonateHCID 57691172(6-(5-Cyclopropylisoxazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methanamineHCID 135987468Tert-butyl (z)-((6-(chloro(hydroxyimino)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)carbamate

生成物 1

HCID 675033553-Methyl-6-((6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)quinazolin-4(3H)-one収率 23%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

(6-(5-cyclopropylisoxazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methanamine. Dissolved (Z)-tert-butyl (6-(chloro(hydroxyimino)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylcarbamate (110 mg, 337 μmol), ethynylcyclopropane (28 μl, 337 μmol), and potassium hydrogencarbonate (67.4 mg, 673 μmol) in 0.3 mL of EtOAc and heated to 60° C. for 12 h to afford the protected intermediate. The solvent was removed by rotary evaporation and the residue was redissolved in dicholoromethane (5 mL) and TFA (2 mL) and stirred for 30 min at room temperature. The solvent was then removed and the residue was redissolved in MeOH. Solid K2CO3 was added and the mixture was stirred for 1 h to free base the title compound. Purified the amine via MPLC (DCM/MeOH+1% NH4OH) to afford the title compound (20 mg, 23% yield).

後処理

  1. customto afford the protected intermediate
  2. customThe solvent was removed by rotary evaporation
  3. dissolutionthe residue was redissolved in dicholoromethane (5 mL) and TFA (2 mL)
  4. customThe solvent was then removed
  5. dissolutionthe residue was redissolved in MeOH
  6. additionSolid K2CO3 was added
  7. stirringthe mixture was stirred for 1 h to free base the title compound
  8. customPurified the amine via MPLC (DCM/MeOH+1% NH4OH)

出典と根拠

ORDレコード
ord-217df8933a304404a0b59e233663bd43
出典データセット
uspto-grants-2012_06
特許番号
US08198448B2

反応ノート

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