Acetic Acid → HCID 136054893, compound

HRID 2051565Notes

Reaction equation

HRID 2051565 reaction equation
[NH2:1][C:2]1[CH:23]=[CH:22][C:5]([C:6]([NH:8][C@H:9]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[O:7])=[CH:4][C:3]=1[O:24][CH3:25].[C:26]([NH:29][C:30]1[NH:31][C:32](=[O:47])[C:33]([CH2:43][CH2:44][CH:45]=O)=[C:34]([N:36]([C:40](=[O:42])[CH3:41])[C:37](=[O:39])[CH3:38])[N:35]=1)(=[O:28])[CH3:27].C(O)(=O)C.C([BH3-])#N.[Na+]>C(O)C.CO>[C:26]([NH:29][C:30]1[NH:31][C:32](=[O:47])[C:33]([CH2:43][CH2:44][CH2:45][NH:1][C:2]2[CH:23]=[CH:22][C:5]([C:6]([NH:8][C@H:9]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:10][CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[O:7])=[CH:4][C:3]=2[O:24][CH3:25])=[C:34]([N:36]([C:37](=[O:39])[CH3:38])[C:40](=[O:42])[CH3:41])[N:35]=1)(=[O:28])[CH3:27]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 14986745HCID 14986745, compoundHCID 135578121HCID 135578121, compound

Product 1

HCID 136054893HCID 136054893, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

Both diethyl N-(4-amino-3-methoxybenzoyl)-(L)-glutamate (3.52 g, 9.99 mmoles) and 3-(2-acetylamino-4-diacetylamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propionaldehyde (3.08 g, 9.99 mmoles) were stirred in absolute ethanol (100 mL) under nitrogen while glacial acetic acid (6 mL) was added dropwise during 1 minute. After solution was achieved (0.5 hour), activated 3 Å molecular sieves (20 mL) were added and stirring was continued 2 hours. The reaction mixture was chilled (ice bath) and sodium cyanoborohydride (628 mg, 9.99 mmoles) added in one portion. After stirring cold 0.5 hour, the bath was removed and the reaction mixture allowed to warm to ambient temperature. The reaction mixture was filtered after 16 hours and the solids were rinsed with ethanol (100 mL). The filtrate was spin evaporated and dried to a cream foam that was dissolved in ethyl acetate (100 mL). The organic phase was washed (2×100 mL 1:1 brine/water) and poured onto a silica gel column (175 g, pre-wet with ethyl acetate). The column was rinsed with ethyl acetate (400 mL) and then the product eluted with 5% added methanol. Like fractions were combined by spin evaporation and dried to give a white solid; yield, 2.07 g (32%); mp 73°-84° C. (eff.); 1H-NMR (DMSO-d6) δ 1.15 and 1.17 (2t overlapped, 6H), 1.65 (br m, 2H) 1.9-2.3 (br m, 4H), 2.12 (s, 3H), 2.20 (s, 6H), 2.40 (t, 2H), 3.10 (br m, 2H), 3.80 (s, 3H), 4.0-4.2 (2 q overlapped, 4H), 4.39 (m, 1H), 5.46 (br t, 1H), 6.47 (d, Jo=8 Hz, 1H), 7.29 (d, Jm=2 Hz, 1H), 7.42 (dxd, Jo=8 Hz, Jm=2 hz, 1H), 8.28 (d, 1H), 11.9 (v br s, 2H); uv (MeOH) 306 nm max (25800), 258 min (3940), 227 sh (17800), 205 max (32400), mass spec (FAB) m/e 645.6 (62%), 442.5 (81), 400.1 (100).

Workup

  1. additionwas added dropwise during 1 minute
  2. custom(0.5 hour), activated 3 Å molecular sieves (20 mL)
  3. additionwere added
  4. additionadded in one portion
  5. stirringAfter stirring cold 0.5 hour
  6. customthe bath was removed
  7. filtrationThe reaction mixture was filtered after 16 hours
  8. washthe solids were rinsed with ethanol (100 mL)
  9. customevaporated
  10. customdried to a cream foam that
  11. dissolutionwas dissolved in ethyl acetate (100 mL)
  12. washThe organic phase was washed (2×100 mL 1:1 brine/water)
  13. additionpoured onto a silica gel column (175 g, pre-wet with ethyl acetate)
  14. washThe column was rinsed with ethyl acetate (400 mL)
  15. washthe product eluted with 5%
  16. additionadded methanol
  17. customLike fractions were combined by spin evaporation
  18. customdried
  19. customto give a white solid
  20. customyield

Sources & evidence

ORD record
ord-4fbc5672a8ca40d1a962bdd57cb27979
Source dataset
uspto-grants-1991_05
Patent number
US05019577

Reaction notes

Loading…