4-Methylmorpholine → HCID 178454204, compound

HRID 1106122Notes

Reaction equation

HRID 1106122 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([OH:14])[C:11]([C:15]([OH:17])=[O:16])=[CH:10][N:9]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:25]([O:29][C:30]([NH:32][C@H:33]([C:39](O)=[O:40])[CH2:34][CH2:35][C:36](=[O:38])[NH2:37])=[O:31])([CH3:28])([CH3:27])[CH3:26].CN1CCOCC1.C(Cl)(=O)C(C)(C)C.N1C=CC=NC=1>C(#N)C>[C:25]([O:29][C:30]([NH:32][C@H:33]([C:39]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:13]=[C:12]([OH:14])[C:11]([C:15]([OH:17])=[O:16])=[CH:10][N:9]=2)=[CH:6][CH:7]=1)=[O:40])[CH2:34][CH2:35][C:36](=[O:38])[NH2:37])=[O:31])([CH3:27])([CH3:28])[CH3:26]

Participants

8

Reactant 6

HCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 9260PyrimidineHCID 62493Pivaloyl chlorideHCID 83687L-Glutamine, N2-((1,1-dimethylethoxy)carbonyl)-HCID 178507442HCID 178507442, compound

Product 1

HCID 178454204HCID 178454204, compoundYield 65.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

A suspension of 5.78 g (25 mmol) of 2-(4-aminophenyl)-4-hydroxy-5-pyrimidine carboxylic acid and 100 ml of acetonitrile is stirred at room temperature and 5.25 g (52 mmol) of triethylamine is added. The mixture is stirred for 1 hr and the resulting solution is added to a solution of mixed anhydride prepared as follows. A suspension of 9.24 g (37.5 mmol) of N-t-butoxycarbonyl-L-glutamine and 200 ml of acetonitrile is stirred at 0° C. and 7.58 g (75 mmol) of N-methylmorpholine is added. The resulting solution is cooled to -30° C. and 4.52 g (37.5 mmol) of pivaloyl chloride is added and stirring is continued at -10°±5° C. for 1 hr. The pyrimidine acid solution is added, keeping the temperature below -10° C., and stirring is continued for 2 hrs and the reaction is placed in an ice bath and allowed to warm to room temperature overnight. The solvent is evaporated and the residue dissolved in ice water. The pH is adjusted to 3.2 with solid citric acid and the resulting precipitate is filtered, washed with water, and redissolved in ethanol. The solution is clarified by filtration and the filtrate evaporated. The residue is triturated with ether, filtered, and the precipitate washed with ether, and dried to give 7.5 g of 2-[4-(N-t-butoxycarbonyl-L-glutaminylamino)phenyl]-4-hydroxy-5-pyrimidine carboxylic acid; [α]D23 -16° (cl, pH 7).

Workup

  1. stirringThe mixture is stirred for 1 hr
  2. customprepared
  3. stirringis stirred at 0° C.
  4. temperatureThe resulting solution is cooled to -30° C.
  5. stirringstirring
  6. customthe temperature below -10° C.
  7. stirringstirring
  8. waitis continued for 2 hrs
  9. customthe reaction is placed in an ice bath
  10. temperatureto warm to room temperature overnight
  11. customThe solvent is evaporated
  12. dissolutionthe residue dissolved in ice water
  13. filtrationthe resulting precipitate is filtered
  14. washwashed with water
  15. dissolutionredissolved in ethanol
  16. filtrationThe solution is clarified by filtration
  17. customthe filtrate evaporated
  18. customThe residue is triturated with ether
  19. filtrationfiltered
  20. washthe precipitate washed with ether
  21. customdried

Sources & evidence

ORD record
ord-40705f0e75f44d438485d71dc7dcedb1
Source dataset
uspto-grants-1982_01
Patent number
US04311699

Reaction notes

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