4-Methylmorpholine → HCID 178471570, compound

HRID 2350867

Reaction equation

HRID 2350867 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH2:9][CH2:10][CH2:11][CH2:12][C:13]2[CH:21]=[CH:20][C:16]([C:17]([OH:19])=O)=[CH:15][CH:14]=2)=[C:4]([OH:22])[N:3]=1.C1(NP(Cl)(=O)OC2C=CC=CC=2)C=CC=CC=1.CN1CCOCC1.Cl.[NH2:48][C@H:49]([C:57]([O:59][CH2:60][CH3:61])=[O:58])[CH2:50][CH2:51][C:52]([O:54][CH2:55][CH3:56])=[O:53]>CN1CCCC1=O>[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH2:9][CH2:10][CH2:11][CH2:12][C:13]2[CH:14]=[CH:15][C:16]([C:17]([NH:48][C@H:49]([C:57]([O:59][CH2:60][CH3:61])=[O:58])[CH2:50][CH2:51][C:52]([O:54][CH2:55][CH3:56])=[O:53])=[O:19])=[CH:20][CH:21]=2)=[C:4]([OH:22])[N:3]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 73960Glutamic acid diethyl ester hydrochlorideHCID 103959Phosphoramidochloridic acid, N-phenyl-, phenyl esterHCID 178508748HCID 178508748, compound

Product 1

HCID 178471570HCID 178471570, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 0.47 g (1.0 eq) of 4-[4-(2,4-diamino-6-hydroxypyrimidin-5-yl)butyl]benzoic acid, 0.62 g (1.5 eq) of phenyl N-phenylphosphoramidochloridate, 0.79 g (5.0 eq) of N-methylmorpholine, and 50 mL of anhydrous N-methylpyrrolidone is stirred under nitrogen at ambient temperatures for one hour. There is then added 0.75 g (2.0 eq) of diethyl L-glutamate hydrochloride and stirring is continued under nitrogen for 24 hours. The solvent is removed by vacuum distillation and chloroform was added to the residue. The chloroform solution is washed with water, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue is chromatographed with 1:9 methanol:chloroform to yield diethyl N-(4-[4-(2,4-diamino-6-hydroxypyrimidin-5-yl)butyl]benzoyl)-L-glutamate, m.p. 75°-76° C.; IR (KBr) vmax 3320, 2920, 2915, 1845, 1720, 1580, 1529, 1427, 1368, 1326, 1192, 1093, 1021, 849 and 750 cm-1 ; 1H NMR (CDCl3) delta 11.58 (bs, 1 H (3)--NH), 7.68 (d, J=7.9 Hz, 2H, Ar), 7.33 (d, J=7.9 Hz, 1H, NH), 7.17 (d, J=7.9 Hz, 2H, Ar), 5.54 (bs, 2H (2)--NH2), 4.76-4.82 (m, 1H, CH), 4.71 (bs, 2H, (6)--NH2), B 4.23 (q, J=7.11 Hz, 2H, CO2CH2), 4.12 (q, J=6.5 Hz, 2H, CO2CH2), 2.15-2.68 (m, 8H, 2° aliphatic) 1.57-1.66 (m, 2H, 2° aliphatic), 1.35-1.45 (m, 2H, 2° aliphatic), 1.30 (t, J=7.1 Hz, 3H, CH3), 1.22 (t, J=7.1 Hz, 3H, CH3); HRMS calcd for C24H33N5O6 (M+): 487.2430; found: 487.2415; other ions at m/e 348, 313, 285, 195, 167, 139, 97, and 84.

Workup

  1. stirringstirring
  2. waitis continued under nitrogen for 24 hours
  3. customThe solvent is removed by vacuum distillation and chloroform
  4. additionwas added to the residue
  5. washThe chloroform solution is washed with water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue is chromatographed with 1:9 methanol

Sources & evidence

ORD record
ord-3065a2d8a5714421b27e16806f836b9b
Source dataset
uspto-grants-1989_10
Patent number
US04871743

Linked notes

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