4-Methylmorpholine → HCID 178471558, compound

HRID 2259446Notes

Reaction equation

HRID 2259446 reaction equation
[C:1]([NH:7][C:8]1[N:9]=[C:10]([OH:29])[C:11]2[CH:17]=[C:16]([CH2:18][CH2:19][C:20]3[CH:28]=[CH:27][C:23]([C:24](O)=[O:25])=[CH:22][CH:21]=3)[CH:15]=[N:14][C:12]=2[N:13]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].C1(NP(Cl)(=O)OC2C=CC=CC=2)C=CC=CC=1.CN1CCOCC1.Cl.[NH2:55][C@H:56]([C:64]([O:66][CH2:67][CH3:68])=[O:65])[CH2:57][CH2:58][C:59]([O:61][CH2:62][CH3:63])=[O:60]>CN1CCCC1=O>[C:1]([NH:7][C:8]1[N:9]=[C:10]([OH:29])[C:11]2[CH:17]=[C:16]([CH2:18][CH2:19][C:20]3[CH:28]=[CH:27][C:23]([C:24]([NH:55][C@H:56]([C:64]([O:66][CH2:67][CH3:68])=[O:65])[CH2:57][CH2:58][C:59]([O:61][CH2:62][CH3:63])=[O:60])=[O:25])=[CH:22][CH:21]=3)[CH:15]=[N:14][C:12]=2[N:13]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 73960Glutamic acid diethyl ester hydrochlorideHCID 103959Phosphoramidochloridic acid, N-phenyl-, phenyl esterHCID 178447252HCID 178447252, compound

Product 1

HCID 178471558HCID 178471558, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 0.19 g (1.0 eq) of 4-[2-(2-pivaloylamino-4-hydroxypyrido[2,3-d]pyrimidin-6-yl)ethyl]benzoic acid 0.19 g (1.5 eq) of phenyl N-phenylphosphoramidochloridate, 0.24 g (5.0 eq) of N-methylmorpholine, and 20 mL of N-methylpyrrolidone is stirred under nitrogen and at room temperature for one hour and 0.23 g (2.0 eq) of diethyl L-glutamate hydrochloride is added. The mixture is stirred for an additional 24 hours under nitrogen and the solvents then removed by evaporation. Chloroform is added and this mixture is then washed with water, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is chromatographed, eluting with 2% methanol/chloroform to yield diethyl N-(4-[2-(2-pivaloylamino-4-hydroxypyrido[2,3-d]pyrimidin-6-yl)ethyl]benzoyl)-L-glutamate. m.p. >250° C.; 1H NMR (CDCl3) delta 8.63 (s, 1H), 8.33 (s, 1H), 7.74 (d, J=8.11 Hz, 2H, Ar), 7.21 (d, J=8.11 Hz, 2H, Ar), 7.19 (d, J=6.9 Hz, 1H, NH), 4.77-4.84 (m, 1H-CH--), 4.24 (q, J=7.4 Hz, 2H, CO2CH2), 4.12 (q, J=7.4 Hz, 2H, COOCH), 3.05 (s, 4H, 2° aliphatic), 1.97-2.61 (m, 4H, 2° aliphatic), 1.34 (s, 9H, t-butyl), 1.29 (t, J=8.4 Hz, 3H, --CH3), 1.22 (t, J=8.4 Hz, 3H, --CH3).

Workup

  1. stirringThe mixture is stirred for an additional 24 hours under nitrogen
  2. customthe solvents then removed by evaporation
  3. additionChloroform is added
  4. washthis mixture is then washed with water
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is chromatographed
  9. washeluting with 2% methanol/chloroform

Sources & evidence

ORD record
ord-9381acd5913140698cd26e10d8827722
Source dataset
uspto-grants-1995_12
Patent number
US05473071

Reaction notes

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