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

HRID 276935Notes

Reaction equation

HRID 276935 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[N:8]1[C:13](=[O:14])[CH:12]=[CH:11][C:10]([C:15]2[C:16]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[N:17][N:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=23)=[N:9]1.C(O[AlH-](OC(C)(C)C)OC(C)(C)C)(C)(C)C.[Li+]>O1CCCC1>[OH:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[N:8]1[C:13](=[O:14])[CH:12]=[CH:11][C:10]([C:15]2[C:16]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)=[N:17][N:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=23)=[N:9]1

Participants

4

Reactant 2

HCID 110690413-[2-(2-Oxocyclohexyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridineHCID 16684435Lithium tritertbutoxyaluminohydride

Product 1

HCID 54253143cis-3-[2-(2-Hydroxycyclohexyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridineYield 99.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
7.5 °C

Procedure

To a suspension of 3-[2-(2-oxocyclohexyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine (679 mg) in 14 ml of tetrahydrofuran was added lithium tri-tert-butoxyaluminohydride (676 mg) at 5° C. The reaction mixture was allowed to stir at 5-10° C. for 45 minutes, then the solvent was removed in vacuo. To the residue was added 20 ml ice-water. Then, the mixture was acidified with 1N hydrochloric acid and extracted with dichloromethane (25 ml×2). The combined extracts were washed with water (20 ml) and brine (20 ml), dried over sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography on silica gel (30 g) eluted with a mixture of dichloromethane and ethyl acetate (10:3) to give pale yellow crystals of cis-3-[2-(2-hydroxycyclohexyl)-3-oxo-2,3-dihydropyridazin-6-yl]-2-phenylpyrazolo[1,5-a]pyridine (677.4 mg).

Workup

  1. customthe solvent was removed in vacuo
  2. additionTo the residue was added 20 ml ice-water
  3. extractionextracted with dichloromethane (25 ml×2)
  4. washThe combined extracts were washed with water (20 ml) and brine (20 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography on silica gel (30 g)
  8. washeluted with a mixture of dichloromethane and ethyl acetate (10:3)

Sources & evidence

ORD record
ord-acbbd037c780465390e11d598fac5dbe
Source dataset
uspto-grants-2002_03
Patent number
US06355640B1

Reaction notes

Loading…