HCID 54692278, compound → HCID 54692421, compound

HRID 1162835Notes

Reaction equation

HRID 1162835 reaction equation
[F:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][N:7]2[CH2:22][CH:21]([CH2:23][CH2:24][N:25](OC)[CH3:26])[N:10]3[C:11](=[O:20])[N:12]([CH:17]([CH3:19])[CH3:18])[C:13](=[O:16])[C:14]([OH:15])=[C:9]3[C:8]2=[O:29])=[CH:4][CH:3]=1>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[CH2:22][CH:21]([CH2:23][CH2:24][NH:25][CH3:26])[N:10]3[C:11](=[O:20])[N:12]([CH:17]([CH3:19])[CH3:18])[C:13](=[O:16])[C:14]([OH:15])=[C:9]3[C:8]2=[O:29])=[CH:30][CH:31]=1

Participants

3

Reactant 1

HCID 54692278HCID 54692278, compound

Product 1

HCID 54692421HCID 54692421, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2-(4-Fluorobenzyl)-9-hydroxy-7-isopropyl-4-{2-[methoxy(methyl)amino]ethyl}-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,6,8(7H)-trione (108 mg, 0.20 mmol, from Example 6) was dissolved in degassed MeOH (8 mL). The solution was degassed and purged three times with nitrogen and then treated with 10% palladium on activated carbon (25 mg) and 6 N aqueous HCl solution (10 drops). The mixture was degassed and purged with nitrogen three times more and placed under hydrogen atmosphere for 24 h. The reaction was filtered through Celite, washing with MeOH, and the filtrate was concentrated in vacuo to a dark yellow oil. Purification by reverse phase chromatography [95:5 water (+0.1% TFA)/MeCN (+0.1% TFA) to 5:95 water (+0.1% TFA)/MeCN (+0.1% TFA)] afforded the title compound as a gray foam. 1H NMR (500 MHz, CD3OD) δ 7.45-7.43 (m, 2H), 7.16-7.12 (m, 2H), 5.19 (dt, J=7.0, 14.0 Hz, 1H), 4.94 (d, J=14.5 Hz, 1H), 4.85-4.84 (m, 1H), 4.50 (d, J=14.5 Hz, 1H), 3.84 (dd, J=4.0, 14.0 Hz, 1H), 3.43 (dd, J=1.5, 14.0 Hz, 1H), 2.92-2.78 (m, 2H), 2.64 (s, 3H), 1.96-1.88 (m, 1H), 1.77-1.70 (m, 1H), 1.47 (dd, J=4.5, 6.5 Hz, 6H). HRMS (FT/ES) M+H: calcd for (C20H26FN4O4)+ 405.1933. found 405.1945.

Workup

  1. customThe solution was degassed
  2. custompurged three times with nitrogen
  3. additiontreated with 10% palladium on activated carbon (25 mg) and 6 N aqueous HCl solution (10 drops)
  4. customThe mixture was degassed
  5. custompurged with nitrogen three times more
  6. filtrationThe reaction was filtered through Celite
  7. washwashing with MeOH
  8. concentrationthe filtrate was concentrated in vacuo to a dark yellow oil
  9. customPurification by reverse phase chromatography [95:5 water (+0.1% TFA)/MeCN (+0.1% TFA) to 5:95 water (+0.1% TFA)/MeCN (+0.1% TFA)]

Sources & evidence

ORD record
ord-c5a3d717c8d24f6cb4a020d4273f4e7d
Source dataset
uspto-grants-2010_10
Patent number
US07820680B2

Reaction notes

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