Tetrahydrofuran → tert-butyl (3S*,5R*)-3-[({2-tert-butyl-4-[(furan-2-ylmethyl)amino]pyrimidin-5-yl}carbonyl)(2-methylpropyl)amino]-5-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)piperidine-1-carboxylate

HRID 2192817Notes

Reaction equation

HRID 2192817 reaction equation
Cl.N[OH:3].[C:4]([C:8]1[N:13]=[C:12]([NH:14][CH2:15][C:16]2[O:17][CH:18]=[CH:19][CH:20]=2)[C:11]([C:21]([N:23]([CH2:42][CH:43]([CH3:45])[CH3:44])[C@H:24]2[CH2:29][C@@H:28]([C:30]3[N:31]=NN[N:34]=3)[CH2:27][N:26]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:25]2)=[O:22])=[CH:10][N:9]=1)([CH3:7])([CH3:6])[CH3:5].C1[CH2:50][O:49]CC1>CO.C(N(CC)CC)C.O>[C:4]([C:8]1[N:13]=[C:12]([NH:14][CH2:15][C:16]2[O:17][CH:18]=[CH:19][CH:20]=2)[C:11]([C:21]([N:23]([CH2:42][CH:43]([CH3:45])[CH3:44])[C@H:24]2[CH2:29][C@@H:28]([C:30]3[NH:31][C:50](=[O:49])[O:3][N:34]=3)[CH2:27][N:26]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:25]2)=[O:22])=[CH:10][N:9]=1)([CH3:7])([CH3:6])[CH3:5]

Participants

7

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 443297Hydroxyamine hydrochlorideHCID 86649291tert-butyl (3S*,5R*)-3-[({2-tert-butyl-4-[(furan-2-ylmethyl)amino]pyrimidin-5-yl}carbonyl)(2-methylpropyl)amino]-5-(2H-tetrazol-5-yl)piperidine-1-carboxylate

Product 1

HCID 136414286tert-butyl (3S*,5R*)-3-[({2-tert-butyl-4-[(furan-2-ylmethyl)amino]pyrimidin-5-yl}carbonyl)(2-methylpropyl)amino]-5-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8471TriethylamineSolvent

Procedure

Hydroxylamine hydrochloride (35 mg) was dissolved in THF (3 ml)-methanol (3 ml), triethylamine (0.07 ml) was added, and the mixture was stirred at room temperature for 1 hr. A solution of tert-butyl (3S*,5R*)-3-[({2-tert-butyl-4-[(furan-2-ylmethyl)amino]pyrimidin-5-yl}carbonyl)(2-methylpropyl)amino]-5-(2H-tetrazol-5-yl)piperidine-1-carboxylate (120 mg) in THF (3 ml) was further added, and the mixture was stirred at 60° C. for 3 hr. The reaction mixture was allowed to cool to room temperature, and diluted with water, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure, and the residue was dissolved in tetrahydrofuran (5 ml). 1,1′-Carbonylbis(1H-imidazole) (72 mg) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.066 ml) were added and the mixture was stirred at room temperature for 30 min. The reaction mixture was concentrated under reduced pressure, diluted with ethyl acetate, washed with 0.5 M hydrochloric acid and saturated brine, and dried over anhydrous magnesium sulfate. The solution was concentrated under reduced pressure, and the residue was subjected to silica gel chromatography. The fraction eluted with ethyl acetate-hexane (10:95) to ethyl acetate was concentrated under reduced pressure to give the object compound (26.1 mg).

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at 60° C. for 3 hr
  3. temperatureto cool to room temperature
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialThe extract was dried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. dissolutionthe residue was dissolved in tetrahydrofuran (5 ml)
  8. addition1,1′-Carbonylbis(1H-imidazole) (72 mg) and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.066 ml) were added
  9. stirringthe mixture was stirred at room temperature for 30 min
  10. concentrationThe reaction mixture was concentrated under reduced pressure
  11. additiondiluted with ethyl acetate
  12. washwashed with 0.5 M hydrochloric acid and saturated brine
  13. dry with materialdried over anhydrous magnesium sulfate
  14. concentrationThe solution was concentrated under reduced pressure
  15. washThe fraction eluted with ethyl acetate-hexane (10:95) to ethyl acetate
  16. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-a7be39d84c68493eb4f37c773af1a13f
Source dataset
uspto-grants-2012_12
Patent number
US08329691B2

Reaction notes

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