Cyclohexene oxide → cis-3-[2-(2-Hydroxycyclohexyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine

HRID 965345Notes

Reaction equation

HRID 965345 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.[H-].[Na+].[O:25]1[CH:27]2[CH2:28][CH2:29][CH2:30][CH2:31][CH:26]12>CN(C)C=O>[OH:25][C@H:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]1[N:3]1[C:2](=[O: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]1

Participants

5

Reactant 3

HCID 9246Cyclohexene oxideHCID 24758Sodium hydrideHCID 105894183(2H)-Pyridazinone, 6-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-

Product 1

HCID 54253143cis-3-[2-(2-Hydroxycyclohexyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridineYield 3.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
5 °C

Procedure

To a solution of 3-(3-oxo-2,3-dihydropyridazin-6-yl)-2-phenylpyrazolo[1,5-a]pyridine (1.58 g) in 80 ml of N,N-dimethylformamide was added sodium hydride (60% dispersion in mineral oil, 242 mg) at 5° C. After being stirred for 15 minutes at 5° C., the mixture was treated with epoxycyclohexane (1.62 g) and heated to 127° C. for 4.5 hours. The reaction mixture was poured into ice-water (200 ml), and the mixture was extracted with ethyl acetate (100 ml, 50 ml). The combined extracts were washed with water (50 ml) and brine (50 ml), dried over sodium sulfate, and concentrated in vacuo. The crude materials were purified by column chromatography on silica gel (40 g). The fractions containing minor cis isomer eluted with a mixture of dichloromethane and ethyl acetate (10:1-10:2) were collected, and the solvent was removed in vacuo to give cis-3-[2-(2-hydroxycyclohexyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine (65.1 mg). The physical data for this compound were idendical with those of the authentic sample prepared by the method described in Example 4.

Workup

  1. temperatureheated to 127° C. for 4.5 hours
  2. extractionthe mixture was extracted with ethyl acetate (100 ml, 50 ml)
  3. washThe combined extracts were washed with water (50 ml) and brine (50 ml)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude materials were purified by column chromatography on silica gel (40 g)
  7. additionThe fractions containing minor cis isomer
  8. washeluted with a mixture of dichloromethane and ethyl acetate (10:1-10:2)
  9. customwere collected
  10. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-0f6545fd694c42fd9df199274cc76499
Source dataset
uspto-grants-1998_06
Patent number
US05773530

Reaction notes

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