Acetic Acid → tert-butyl {(5R,6S,8S)-5-methyl-6-phenyl-3-[1-(trifluoromethyl)cyclopropyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-yl}carbamate

HRID 2179471Notes

Reaction equation

HRID 2179471 reaction equation
[C:1]([O:5][C:6](=[O:23])[NH:7][C@H:8]1[CH2:13][C@@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C@@H:11]([CH3:20])[NH:10][C:9]1=[N:21][NH2:22])([CH3:4])([CH3:3])[CH3:2].[F:24][C:25]([F:33])([F:32])[C:26]1([C:29](O)=O)[CH2:28][CH2:27]1.ON1C2N=CC=CC=2N=N1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.C(=O)(O)[O-].C(O)(=O)C>ClCCl.C(#N)C>[C:1]([O:5][C:6](=[O:23])[NH:7][C@H:8]1[CH2:13][C@@H:12]([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C@@H:11]([CH3:20])[N:10]2[C:29]([C:26]3([C:25]([F:33])([F:32])[F:24])[CH2:28][CH2:27]3)=[N:22][N:21]=[C:9]12)([CH3:2])([CH3:3])[CH3:4]

Participants

10

Reactant 7

HCID 176Acetic AcidHCID 769Bicarbonate Ion2×HCID 79724-MethylmorpholineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27783061-(Trifluoromethyl)cyclopropane-1-carboxylic acidHCID 178461610HCID 178461610, compound

Product 1

HCID 86698236tert-butyl {(5R,6S,8S)-5-methyl-6-phenyl-3-[1-(trifluoromethyl)cyclopropyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine-8-yl}carbamate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of crude tert-butyl[(3S,5S,6R)-2-hydrazinylidene-6-methyl-5-phenylpiperidin-3-yl]carbamate (99 mg, 0.31 mmol) in dichloromethane (3.1 mL) was added 1-(trifluoromethyl)cyclopropanecarboxylic acid (58 mg, 0.37 mmol), 1-hydroxy-7-azabenzotriazole (4.3 mg, 0.031 mmol), N-methylmorpholine (82 μL, 0.75 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (72 mg, 0.37 mmol). The mixture was stirred 1 h. Saturated aqueous bicarbonate was added, and the resulting mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Acetonitrile (12.5 mL) and glacial acetic acid (18 μL, 0.31 mmol) were added and the resulting mixture stirred at 70° C. for 90 min. Saturated aqueous bicarbonate was added, and the resulting mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated giving the crude title compound. MS 437.2 (M+1).

Workup

  1. extractionthe resulting mixture was extracted with ethyl acetate (3×)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. stirringthe resulting mixture stirred at 70° C. for 90 min
  7. extractionthe resulting mixture was extracted with ethyl acetate (3×)
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-dce728c7541e4c6a8c552f10c7819ece
Source dataset
uspto-grants-2015_06
Patent number
US09067941B2

Reaction notes

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