Cyclopropylacetylene → (6-(5-Cyclopropylisoxazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methanamine

HRID 40395

반응식

HRID 40395 반응식
Cl/[C:2](=[N:21]\[OH:22])/[C:3]1[CH:4]=[CH:5][C:6]2[N:7]([C:9]([CH2:12][NH:13]C(=O)OC(C)(C)C)=[N:10][N:11]=2)[N:8]=1.[C:23]([CH:25]1[CH2:27][CH2:26]1)#[CH:24].C(=O)([O-])O.[K+]>CCOC(C)=O>[CH:25]1([C:23]2[O:22][N:21]=[C:2]([C:3]3[CH:4]=[CH:5][C:6]4[N:7]([C:9]([CH2:12][NH2:13])=[N:10][N:11]=4)[N:8]=3)[CH:24]=2)[CH2:27][CH2:26]1

참가 물질

5

반응물 3

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

생성물 1

HCID 57691172(6-(5-Cyclopropylisoxazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methanamine수율 23.2%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

반응 조건

온도
60 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-9b2ff99cc9894567a238340229554b83
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524900B2

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