HCID 67332979, compound → HCID 86656374, compound

HRID 1942559Notes

Reaction equation

HRID 1942559 reaction equation
[CH2:1]([N:8](C(OCC1C=CC=CC=1)=O)[CH2:9][CH2:10][N:11]1[C:16]2[CH:17]=[C:18]([C:25]([N:27]([CH:41]([CH3:43])[CH3:42])[C@@H:28]3[CH2:33][CH2:32][CH2:31][N:30]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:29]3)=[O:26])[C:19]([C:21]([F:24])([F:23])[F:22])=[CH:20][C:15]=2[O:14][C:13]([CH3:52])([CH2:44][O:45][CH:46]2[CH2:51][CH2:50]CCO2)[C:12]1=[O:53])[C:2]1C=CC=C[CH:3]=1>CO.[Pd]>[CH:41]([N:27]([C:25]([C:18]1[C:19]([C:21]([F:22])([F:23])[F:24])=[CH:20][C:15]2[O:14][C:13]([CH3:52])([CH2:44][O:45][C:46]#[C:51][CH3:50])[C:12](=[O:53])[N:11]([CH2:10][CH2:9][NH:8][C:1]#[C:2][CH3:3])[C:16]=2[CH:17]=1)=[O:26])[C@@H:28]1[CH2:33][CH2:32][CH2:31][N:30]([C:34]([O:36][C:37]([CH3:38])([CH3:39])[CH3:40])=[O:35])[CH2:29]1)([CH3:43])[CH3:42]

Participants

4

Reactant 1

HCID 67332979HCID 67332979, compound

Product 1

HCID 86656374HCID 86656374, compoundYield 29.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

tert-Butyl (3R)-3-[{[4-(2-{benzyl[(benzyloxy)carbonyl]amino}ethyl)-2-methyl-3-oxo-2-[(tetrahydro-2H-pyran-2-yloxy)methyl]-7-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazin-6-yl]carbonyl}(isopropyl)amino]piperidine-1-carboxylate (24.9 g) was dissolved in methanol (300 mL), and thereto was added a 10% palladium/carbon (50% wet.: 30.0 g), and the mixture was vigorously stirred under hydrogen atmosphere at room temperature for 36 hours. After the reaction was complete, the mixture was filtered on celite, washed with ethyl acetate, and the filtrate was concentrated under reduced pressure. tert-Butyl (3R)-3-[{[4-(2-aminomethyl)-2-(hydroxymethyl)-2-methyl-3-oxo-7-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazin-6-yl]carbonyl}(isopropyl)amino]piperidine-1-carboxylate was dissolved in dichloromethane (300 ml), and thereto were added propionyl chloride (2.7 ml) and triethylamine (6.5 mL), and the mixture was stirred for one hour. To the reaction solution was added a saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with chloroform. The organic layer was dried over sodium sulfate, filtered, concentrated under reduced pressure. The obtained residue was purified by column chromatography to give the title compound (5.48 g).

Workup

  1. filtrationthe mixture was filtered on celite
  2. washwashed with ethyl acetate
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. dissolutiontert-Butyl (3R)-3-[{[4-(2-aminomethyl)-2-(hydroxymethyl)-2-methyl-3-oxo-7-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazin-6-yl]carbonyl}(isopropyl)amino]piperidine-1-carboxylate was dissolved in dichloromethane (300 ml)
  5. additionwere added propionyl chloride (2.7 ml) and triethylamine (6.5 mL)
  6. stirringthe mixture was stirred for one hour
  7. additionTo the reaction solution was added a saturated aqueous sodium hydrogen carbonate solution
  8. extractionthe mixture was extracted with chloroform
  9. dry with materialThe organic layer was dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe obtained residue was purified by column chromatography

Sources & evidence

ORD record
ord-6903c523bbce4f7abfbec0e7a2c8ec5e
Source dataset
uspto-grants-2013_03
Patent number
US08389511B2

Reaction notes

Loading…