HCID 11858050, compound → HCID 11858224, compound

HRID 1710757Notes

Reaction equation

HRID 1710757 reaction equation
[CH:1]1([CH2:4][N:5]([CH2:30][CH2:31][CH3:32])[C:6]([C:8]2[O:12][C:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:27][CH2:26][CH2:25][CH:24]4[CH3:28])=[CH:15][CH:14]=3)=[N:10][C:9]=2[CH3:29])=O)[CH2:3][CH2:2]1>O1CCCC1>[CH:1]1([CH2:4][N:5]([CH2:6][C:8]2[O:12][C:11]([C:13]3[CH:14]=[CH:15][C:16]([O:19][CH2:20][CH2:21][CH2:22][N:23]4[CH2:27][CH2:26][CH2:25][CH:24]4[CH3:28])=[CH:17][CH:18]=3)=[N:10][C:9]=2[CH3:29])[CH2:30][CH2:31][CH3:32])[CH2:2][CH2:3]1

Participants

3

Reactant 1

HCID 11858050HCID 11858050, compound

Product 1

HCID 11858224HCID 11858224, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of N-(cyclopropylmethyl)-4-methyl-2-{4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl}-N-propyl-1,3-oxazole-5-carboxamide 97 (0.25 g, 0.57 mmol, 1 eq) in tetrahydrofuran (15 ml) is treated with borane-tetrahydrofuran complex 1 M in tetrahydrofuran (2.2 ml, 2.2 mmol, 4 eq) and refluxed overnight. The solvent is then removed under reduced pressure and the residue is taken up in ethyl acetate and washed with a saturated solution of aqueous ammonium chloride. The organic layer is dried over magnesium sulfate, filtered and concentrated. The residue is then dissolved in tetrahydrofuran and a 2 N sodium hydroxide solution is added to reach pH 10. The mixture is refluxed for 40 h and a saturated solution of aqueous ammonium chloride is added and the solution extracted two times with ethyl acetate. The organic layers are dried over magnesium sulfate, filtered and concentrated under vacuum. Purification by chromatography over silicagel (eluent: dichloromethane/methanol/ammonia 96/3.6/0.4) gives 0.115 g of N-(cyclopropylmethyl)-N-[(4-methyl-2-{4-[3-(2-methylpyrrolidin-1-yl)propoxy]phenyl}-1,3-oxazol-5-yl)methyl]-N-propylamine 112.

Workup

  1. temperaturerefluxed overnight
  2. customThe solvent is then removed under reduced pressure
  3. washwashed with a saturated solution of aqueous ammonium chloride
  4. dry with materialThe organic layer is dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe residue is then dissolved in tetrahydrofuran
  8. additiona 2 N sodium hydroxide solution is added
  9. temperatureThe mixture is refluxed for 40 h
  10. additiona saturated solution of aqueous ammonium chloride is added
  11. extractionthe solution extracted two times with ethyl acetate
  12. dry with materialThe organic layers are dried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under vacuum
  15. customPurification by chromatography over silicagel (eluent: dichloromethane/methanol/ammonia 96/3.6/0.4)

Sources & evidence

ORD record
ord-18b8cf066dfe42d0a754e4b5f6d02b95
Source dataset
uspto-grants-2010_09
Patent number
US07790720B2

Reaction notes

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