Tetrahydrofuran → Cyclopropyl-{4-[3-(1-cyclopropylpiperidin-4-yl)[1,2,4]oxadiazol-5-yl]phenyl}methanone, Hydrochloride

HRID 1715768Notes

Reaction equation

HRID 1715768 reaction equation
[Mg].C1(Br)CC1.[CH:6]1([N:9]2[CH2:14][CH2:13][CH:12]([C:15]3[N:19]=[C:18]([C:20]4[CH:27]=[CH:26][C:23](C#N)=[CH:22][CH:21]=4)[O:17][N:16]=3)[CH2:11][CH2:10]2)[CH2:8][CH2:7]1.[Cl-:28].[NH4+].[CH2:30]1[CH2:34][O:33][CH2:32][CH2:31]1>>[ClH:28].[CH:30]1([C:34]([C:23]2[CH:26]=[CH:27][C:20]([C:18]3[O:17][N:16]=[C:15]([CH:12]4[CH2:11][CH2:10][N:9]([CH:6]5[CH2:8][CH2:7]5)[CH2:14][CH2:13]4)[N:19]=3)=[CH:21][CH:22]=2)=[O:33])[CH2:31][CH2:32]1

Participants

6

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 25517Ammonium ChlorideHCID 78037BromocyclopropaneHCID 5462224MagnesiumHCID 596577884-[3-(1-Cyclopropylpiperidin-4-yl)[1,2,4]oxadiazol-5-yl]benzonitrile

Product 1

HCID 68811587Cyclopropyl-{4-[3-(1-cyclopropylpiperidin-4-yl)[1,2,4]oxadiazol-5-yl]phenyl}methanone, Hydrochloride

Procedure

To a Grignard mixture (prepared from magnesium (50 mg, 2.1 mmol) and cyclopropylbromide (211 mg, 1.7 mmol) in dry THF (2 ml)) placed under an atmosphere of nitrogen was added dropwise a solution of 4-[3-(1-cyclopropylpiperidin-4-yl)[1,2,4]oxadiazol-5-yl]benzonitrile (250 mg, 0.85 mmol, prepared as described in Example 37) in dry THF (1.5 ml). When addition was complete the mixture was heated at reflux for 1 h. The mixture was allowed to cool and then saturated ammonium chloride (1 ml) was added. The mixture was extracted with ethyl acetate (15 ml) and the organic phase was dried (MgSO4) and the solvent was evaporated. The residue was dissolved in a mixture of ethanol (10 ml) and 1 N hydrochloric acid (1 ml) and the solvents were evaporated. The residue was re-evaporated with acetonitril and then stirred with ethyl acetate. This afforded 0.23 g containing the title compound. HPLC: Rt=12.45 min.

Workup

  1. additionWhen addition
  2. temperaturewas heated
  3. temperatureat reflux for 1 h
  4. temperatureto cool
  5. extractionThe mixture was extracted with ethyl acetate (15 ml)
  6. dry with materialthe organic phase was dried (MgSO4)
  7. customthe solvent was evaporated
  8. dissolutionThe residue was dissolved in a mixture of ethanol (10 ml) and 1 N hydrochloric acid (1 ml)
  9. customthe solvents were evaporated
  10. customThe residue was re-evaporated with acetonitril
  11. additionThis afforded 0.23 g containing the title compound

Sources & evidence

ORD record
ord-5d314ae411ef43c19861eed7b473b54e
Source dataset
uspto-grants-2010_09
Patent number
US07799924B2

Reaction notes

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