Ammonia → HCID 53744780, compound

HRID 1358487Notes

Reaction equation

HRID 1358487 reaction equation
[Si]([O:8][CH2:9][C@H:10]([N:23]1[CH:27]=[C:26]([C:28]([O-:30])=O)[N:25]=[CH:24]1)[CH2:11][CH2:12][N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([CH3:22])=[CH:14]1)(C(C)(C)C)(C)C.[Cl-].[NH4+].N.[N+:34](CCCC)(CCCC)(CCCC)CCCC.[F-].C([O-])(C)=O.[NH4+]>CN(C=O)C.C1COCC1.O>[OH:8][CH2:9][C@H:10]([N:23]1[CH:27]=[C:26]([C:28]([NH2:34])=[O:30])[N:25]=[CH:24]1)[CH2:11][CH2:12][N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([CH3:22])=[CH:14]1

Participants

9

Reactant 5

HCID 222AmmoniaHCID 25517Ammonium ChlorideHCID 517165Ammonium AcetateHCID 2724141Tetrabutylammonium FluorideHCID 21137583HCID 21137583, compound

Product 1

HCID 53744780HCID 53744780, compoundYield 103%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
100 °C

Procedure

To a solution of 1-[(R)-1-(tert-butyldimethylsilyloxy)-4-(3-methylindol-1-yl)-2-butyl]imidazol-4-carboxylate (200 mg, 0.45 mmol) in DMF (5 ml) were added ammonium chloride (6 mg, 0.11 mmol) and aqueous 28% NH3 solution (10 ml). And the mixture was heated at 100° C. in a sealed steel tube for 8 hours. After cooling, the reaction mixture was poured into water (50 ml) and extracted with ethyl acetate. The organic layer was washed with brine, dried (magnesium sulfate), and concentrated in vacuo. This material was used for the next reaction without further purification. To an ice cooled solution of the carboxamide prepared above (184 mg) in THF (10 ml) was added dropwise 1.0 M Bu4NF in THF (453 ml). After the addition was completed, the reaction mixture was stirred at ice-bath temperature for 1 hour. 25% AcONH4 (5 ml) was added, and the resulting mixture was stirred for several minutes and then extracted with ethyl acetate. The organic layer was washed with brine, dried (sodium sulfate) and concentrated in vacuo. The residue was triturated with a mixed solvent of isopropyl ether and chloroform (20:1). The resulting precipitates were collected by filtration and washed with the same mixed solvent, and dried in vacuo to give 1-[(R)-1-hydroxy-4-(3-methylindol-1-yl)-2-butyl]-imidazole-4-carboxamide (146 mg, 103%) as a white solid.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried (magnesium sulfate)
  5. concentrationconcentrated in vacuo
  6. customThis material was used for the next reaction without further purification
  7. additionAfter the addition
  8. stirringthe resulting mixture was stirred for several minutes
  9. extractionextracted with ethyl acetate
  10. washThe organic layer was washed with brine
  11. dry with materialdried (sodium sulfate)
  12. concentrationconcentrated in vacuo
  13. customThe residue was triturated with a mixed solvent of isopropyl ether and chloroform (20:1)
  14. customThe resulting precipitates
  15. filtrationwere collected by filtration
  16. washwashed with the same mixed solvent
  17. customdried in vacuo

Sources & evidence

ORD record
ord-f905d26b10f64a8db12488795052334c
Source dataset
uspto-grants-2003_07
Patent number
US06596738B1

Reaction notes

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