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

HRID 2192818Notes

Reaction equation

HRID 2192818 reaction equation
Cl.NO.[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].C1C[O:49][CH2:48]C1>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[N:31]=[CH:48][O:49][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 86649293tert-butyl (3S*,5R*)-3-[({2-tert-butyl-4-[(furan-2-ylmethyl)amino]pyrimidin-5-yl}carbonyl)(2-methylpropyl)amino]-5-(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. The obtained residue was dissolved in trimethyl orthoformate (5 ml), 4-methylbenzenesulfonic acid (20 mg) was added and the mixture was stirred at 100° C. for 10 hr. The reaction mixture was concentrated under reduced pressure, and the residue was subjected to silica gel chromatography. The fraction eluted with ethyl acetate-hexane (5:95-50:50) was concentrated under reduced pressure to give the object compound (72.6 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 obtained residue was dissolved in trimethyl orthoformate (5 ml)
  8. addition4-methylbenzenesulfonic acid (20 mg) was added
  9. stirringthe mixture was stirred at 100° C. for 10 hr
  10. concentrationThe reaction mixture was concentrated under reduced pressure
  11. washThe fraction eluted with ethyl acetate-hexane (5:95-50:50)
  12. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-828b0bb76a63495ca622293864f79a82
Source dataset
uspto-grants-2012_12
Patent number
US08329691B2

Reaction notes

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