HCID 68433138, compound → HCID 68431466, compound

HRID 1162850Notes

Reaction equation

HRID 1162850 reaction equation
[C:1]([O:7][C:8]1[C:13](=[O:14])[N:12]([CH:15]([CH3:17])[CH3:16])[C:11](=[O:18])[N:10]2[CH:19]([CH2:32][CH2:33][O:34]CC3C=CC=CC=3)[CH2:20][N:21]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C:22](=[O:23])[C:9]=12)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[H][H]>C(OCC)(=O)C>[C:1]([O:7][C:8]1[C:13](=[O:14])[N:12]([CH:15]([CH3:17])[CH3:16])[C:11](=[O:18])[N:10]2[CH:19]([CH2:32][CH2:33][OH:34])[CH2:20][N:21]([CH2:24][C:25]3[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=3)[C:22](=[O:23])[C:9]=12)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]

Participants

4

Reactant 2

HCID 68433138HCID 68433138, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 68431466HCID 68431466, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-[2-(benzyloxy)ethyl]-2-(4-fluorobenzyl)-7-isopropyl-1,6,8-trioxo-1,3,4,6,7,8-hexahydro-2H-pyrazino[1,2-c]pyrimidin-9-yl pivalate (918 mg, 1.62 mmol) and 10% Pd(C) (92 mg) in ethyl acetate (32 mL) was stirred under a balloon atmosphere of hydrogen for 24 h. The reaction mixture was filtered through Celite, fresh catalyst was added and the mixture subjected to balloon hydrogenation for an additional 24 h. Analysis by LCMS showed slow conversion to the alcohol, so the mixture was again filtered through Celite and the filtrate was concentrated. The residual solid was taken up in ethanol (32 mL) with a small amount of ethyl acetate added to aid dissolution of the material. 10% Pd(C) was added and the mixture subjected to balloon hydrogenation for 96 h, with fresh catalyst being added after the first 24 h. The reaction still appeared to be progressing slowly, so the mixture was filtered through Celite and Pearlman's catalyst was added to the filtrate. Hydrogenation (balloon) was complete after 48 h (fresh Pearlman's catalyst was added after the first 24 h). Filtration through Celite and concentration afforded the title compound as a foamy white solid. 1H NMR (CDCl3, 400 MHz): δ 7.28-7.26 (m, 2 H), 7.07-7.02 (m, 2 H), 5.21-5.14 (m, 1 H), 4.87-4.74 (m, 2 H), 4.48-4.36 (m, 1 H), 3.89-3.77 (m, 1 H), 3.49-3.25 (m, 3 H), 1.68-1.54 (m, 2H), 1.46 (d, J=6.8 MHz, 6 H), 1.40 (s, 9 H). ES MS (M+1): 476.5.

Workup

  1. filtrationThe reaction mixture was filtered through Celite, fresh catalyst
  2. additionwas added
  3. customfor an additional 24 h
  4. filtrationso the mixture was again filtered through Celite
  5. concentrationthe filtrate was concentrated
  6. additionadded
  7. dissolutiondissolution of the material
  8. addition10% Pd(C) was added
  9. customfor 96 h
  10. additionwith fresh catalyst being added after the first 24 h
  11. customThe reaction
  12. filtrationwas filtered through Celite and Pearlman's catalyst
  13. additionwas added to the filtrate
  14. addition(fresh Pearlman's catalyst was added after the first 24 h)
  15. filtrationFiltration
  16. concentrationthrough Celite and concentration

Sources & evidence

ORD record
ord-c809cce5869c4d73821901ab05acdc9d
Source dataset
uspto-grants-2010_10
Patent number
US07820680B2

Reaction notes

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