Acetic Acid → HCID 136166734, compound

HRID 2051559Notes

Reaction equation

HRID 2051559 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[F:24].[C:25]([NH:28][C:29]1[NH:30][C:31](=[O:46])[C:32]([CH2:42][CH2:43][CH:44]=O)=[C:33]([N:35]([C:39](=[O:41])[CH3:40])[C:36](=[O:38])[CH3:37])[N:34]=1)(=[O:27])[CH3:26].C(O)(=O)C.C([BH3-])#N.[Na+]>C(O)C.CO>[C:25]([NH:28][C:29]1[NH:30][C:31](=[O:46])[C:32]([CH2:42][CH2:43][CH2:44][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[F:24])=[C:33]([N:35]([C:36](=[O:38])[CH3:37])[C:39](=[O:41])[CH3:40])[N:34]=1)(=[O:27])[CH3:26]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 14730655HCID 14730655, compoundHCID 135578121HCID 135578121, compound

Product 1

HCID 136166734HCID 136166734, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

Both diethyl N-(4-amino-3-fluorobenzoyl)-(L)-glutamate (2.21 g, 6.49 mmoles) and 3-(2-acetylamino-4-diacetylamino-1,6-dihydro-6-oxo-5-pyrimidinyl)propionaldehyde (2.00 g, 6.49 mmoles) were stirred in absolute ethanol (50 mL) under nitrogen while glacial acetic acid (3mL) was added dropwise during 1 minute. After solution was achieved (1 hour), activated 3 Å molecular sieves (10 mL) were added and stirring was continued 5 hours. The reaction mixture was chilled (ice bath) and sodium cyanoborohydride (408 mg, 6.49 mmoles) added in one portion. After stirring cold 0.5 hour, the bath was removed. The reaction mixture was allowed to warm to ambient temperature and stir 16 hours. The reaction mixture was filtered and the solids rinsed with ethanol (100 mL). The filtrate was spin evaporated to a brown residue that was partitioned between ethyl acetate and water (100 mL each). The organic phase was separated, washed (1×100 mL 1:1 water/brine), dried (MgSO4), filtered, and spin evaporated to a small volume (20 mL). The solution was chromatographed on silica gel (175 g) using an ethyl acetate rinse (450 mL) followed by elution of the product with 5% added methanol. Like fractions were combined by spin evaporation and dried to give a white solid; yield, 2.66 g (65%); mp 76°-84° C. (dec); 1H-NMR (DMSO-d6) δ 1.15 and 1.16 (2t overlapped, 6H), 1.64 (m, 2H), 2.00 (m, 2H), 2.11 (s, 3H), 2.20 (s, 6H), 2.27 (m, 2H), 2.40 (t, 2H), 3.10 (m, 2H), 3.9-4.1 (2q overlapped, 4H), 4.35 (m, 1H), 6.10 (m, 1H), 6.66 (t, JoH,H and JmF,H =9 Hz, 1H), 7.5-7.6 (m, 2H), 8.35 (d, 1H), 11.9 (v br d, 1H); uv (MeOH) 299 nm max (28000), 257 min (7500); mass spec (FAB) m/e 633 (23%), 430 (100), 388 (87).

Workup

  1. additionwas added dropwise during 1 minute
  2. custom(1 hour), activated 3 Å molecular sieves (10 mL)
  3. additionwere added
  4. additionadded in one portion
  5. stirringAfter stirring cold 0.5 hour
  6. customthe bath was removed
  7. stirringstir 16 hours
  8. filtrationThe reaction mixture was filtered
  9. washthe solids rinsed with ethanol (100 mL)
  10. customevaporated to a brown residue that
  11. customwas partitioned between ethyl acetate and water (100 mL each)
  12. customThe organic phase was separated
  13. washwashed (1×100 mL 1:1 water/brine)
  14. dry with materialdried (MgSO4)
  15. filtrationfiltered
  16. customspin evaporated to a small volume (20 mL)
  17. customThe solution was chromatographed on silica gel (175 g)
  18. washrinse (450 mL)
  19. washfollowed by elution of the product with 5%
  20. additionadded methanol
  21. customLike fractions were combined by spin evaporation
  22. customdried
  23. customto give a white solid
  24. customyield

Sources & evidence

ORD record
ord-16661a997565469a9f94cd0d97a313b5
Source dataset
uspto-grants-1991_05
Patent number
US05019577

Reaction notes

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