18-Crown-6 → (E)-3-[2-(2-methoxycarbonylmethylenecyclohexyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine

HRID 276939Notes

Reaction equation

HRID 276939 reaction equation
[O:1]=[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)=[N:4][NH:3]1.CC(C)([O-])C.[K+].C1OCCOCCOCCOCCOCCOC1.CS(O[CH:52]1[CH2:57][CH2:56][CH2:55][CH2:54]/[C:53]/1=[CH:58]\[C:59]([O:61][CH3:62])=[O:60])(=O)=O>CN(C)C=O>[CH3:62][O:61][C:59](/[CH:58]=[C:53]1/[CH:52]([N:3]2[C:2](=[O:1])[CH:7]=[CH:6][C:5]([C:8]3[C:9]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)=[N:10][N:11]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=34)=[N:4]2)[CH2:57][CH2:56][CH2:55][CH2:54]/1)=[O:60]

Participants

6

Reactant 4

HCID 2855718-Crown-6HCID 105894183(2H)-Pyridazinone, 6-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-HCID 22629181(E)-1-methylsulfonyloxy-2-methoxycarbonylmethylenecyclohexaneHCID 23665647Potassium tert-butoxide

Product 1

HCID 22629241(E)-3-[2-(2-methoxycarbonylmethylenecyclohexyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridineYield 46.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 3-(3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazolo[1,5-a]pyridine (271 mg) in N,N-dimethylformamide (6 ml) was added potassium tert-butoxide (111 mg) and 18-crown-6 (24.8 mg) at 5° C. To this solution was added a solution of (E)-1-methylsulfonyloxy-2-methoxycarbonylmethylenecyclohexane (467 mg) in N,N-dimethylformamide (2 ml) was added dropwise. The reaction mixture was stirred at room temperature for 1 hour and then heated at 110 to 125° C. for 7 hours. The reaction mixture was poured into ice water (30 ml) and extracted with ethyl acetate (20 ml×2). The combined extracts were washed with water (20 ml) and brine (20 ml), dried over anhydrous magnesium sulfate, and evaporated in vacuo. The crude material was purified by column chromatography on SiO2 using a mixture of dichloromethane and ethyl acetate (20:1) as an eluant to give colorless crystals of (E)-3-[2-(2-methoxycarbonylmethylenecyclohexyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine (191.4 mg).

Workup

  1. additionwas added dropwise
  2. temperatureheated at 110 to 125° C. for 7 hours
  3. extractionextracted with ethyl acetate (20 ml×2)
  4. washThe combined extracts were washed with water (20 ml) and brine (20 ml)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customevaporated in vacuo
  7. customThe crude material was purified by column chromatography on SiO2 using
  8. additiona mixture of dichloromethane and ethyl acetate (20:1) as an eluant

Sources & evidence

ORD record
ord-fcfca344a1074acf8e7c7e920bb9a742
Source dataset
uspto-grants-2002_03
Patent number
US06355640B1

Reaction notes

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