Acetic Acid → HCID 136023090, compound

HRID 2051561Notes

Reaction equation

HRID 2051561 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[CH3:24].[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[CH3:24])=[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 14986741HCID 14986741, compoundHCID 135578121HCID 135578121, compound

Product 1

HCID 136023090HCID 136023090, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent

Procedure

Both diethyl N-(4-amino-3-methylbenzoyl)-(L)-glutamate (2.18 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 (3 mL) 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 and the reaction mixture allowed to warm to ambient temperature. The solids were filtered and rinsed with ethanol (100 mL) after 16 hours. The filtrate was spin evaporated to a 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 (15 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 clear semi-solid; yield, 1.45 g (36%); 1H-NMR (DMSO-d 6) δ 1.15 and 1.16 (2t overlapped, 6H), 1.66 (m, 2H), 2.00 (m, 2H), 2.08 (s, 3H), 2.11 (s, 3H), 2.19 (s, 6H), 2.29 (m, 2H), 2.39 (t, 2H), 3.11 (m, 2H), 3.9-4.1 (2q overlapped, 4H), 4.33 (m, 1H), 5.46 (m, 1H), 6.47 (d, Jo=8 Hz, 1H), 7.53 (s, 1H), 7.57 (d, Jo=8 Hz, 1H), 8.20 (d, 1H), 11.8 (v br s, 1H); uv (MeOH) 301 nm max (31000), 258 min (6050); mass spec (FAB) m/e 628 (8%), 426 (100), 384 (95).

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. filtrationThe solids were filtered
  8. washrinsed with ethanol (100 mL) after 16 hours
  9. customevaporated to a residue that
  10. customwas partitioned between ethyl acetate and water (100 mL each)
  11. customThe organic phase was separated
  12. washwashed (1×100 mL 1:1 water/brine)
  13. dry with materialdried (MgSO4)
  14. filtrationfiltered
  15. customspin evaporated to a small volume (15 mL)
  16. customThe solution was chromatographed on silica gel (175 g)
  17. washrinse (450 mL)
  18. washfollowed by elution of the product with 5%
  19. additionadded methanol
  20. customLike fractions were combined by spin evaporation
  21. customdried
  22. customto give a clear semi-solid
  23. customyield

Sources & evidence

ORD record
ord-1ca95f6ec5a34186b3a5c0ea5048d83e
Source dataset
uspto-grants-1991_05
Patent number
US05019577

Reaction notes

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