4-Methylmorpholine → HCID 178471555, Verbindung

HRID 231298

Reaktionsgleichung

Reaktionsgleichung von HRID 231298
[C:1]([NH:4][C:5]1[N:6]=[C:7]([OH:26])[C:8]2[CH:14]=[C:13]([CH:15]=[CH:16][C:17]3[CH:22]=[CH:21][C:20]([C:23](O)=[O:24])=[CH:19][CH:18]=3)[CH:12]=[N:11][C:9]=2[N:10]=1)(=[O:3])[CH3:2].CN1CCOCC1.C1(NP(Cl)(=O)OC2C=CC=CC=2)C=CC=CC=1.Cl.[NH2:52][C@H:53]([C:61]([O:63][CH2:64][CH3:65])=[O:62])[CH2:54][CH2:55][C:56]([O:58][CH2:59][CH3:60])=[O:57]>CN1CCCC1=O>[C:1]([NH:4][C:5]1[N:6]=[C:7]([OH:26])[C:8]2[CH:14]=[C:13]([CH:15]=[CH:16][C:17]3[CH:22]=[CH:21][C:20]([C:23]([NH:52][C@H:53]([C:61]([O:63][CH2:64][CH3:65])=[O:62])[CH2:54][CH2:55][C:56]([O:58][CH2:59][CH3:60])=[O:57])=[O:24])=[CH:19][CH:18]=3)[CH:12]=[N:11][C:9]=2[N:10]=1)(=[O:3])[CH3:2]

Komponenten

6

Edukt 4

HCID 79724-MethylmorpholineHCID 73960Glutamic acid diethyl ester hydrochlorideHCID 103959Phosphoramidochloridic acid, N-phenyl-, phenyl esterHCID 178474467HCID 178474467, Verbindung

Produkt 1

HCID 178471555HCID 178471555, VerbindungAusbeute 66 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To an ice cold solution of 1.5 g (0.0043 mol) of 2-acetamido-4-hydroxy-6-[2-(4-carboxyphenyl)ethenyl]pyrido[2,3-d]pyrimidine in 40 mL of N-methylpyrrolidone containing 1.4 mL of N-methylmorpholine was added 1.72 g (0.0064 mol) of phenyl N-phenylphosphoramidochloridate in a single portion. The resulting mixture was stirred at 0° C. for 30 minutes. Diethyl L-glutamate hydrochloride (1.53 g, 0.0064 mol) was then added and the reaction mixture was stirred at room temperature overnight. The solvent was evaporated under reduced pressure and the residual solid triturated with 50 mL of 1N aqueous sodium carbonate. The mixture was filtered and the collected solid dissolved in 20 mL of chloroform. The chloroform solution was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated to dryness and chromatographed on silica gel. Elution with chloroform:methanol (95:5) gave 1.52 g (66%) of the title compound, which may be alternatively named as diethyl 2-acetyl-5,10-dideaza-9,10-didehydrofolate, mp >250° C.; NMR (CDCl3Me2SO-d6) delta 1.15-1.45 (2t, 6H, J=6 Hz), 2.0-2.65 (m, 4H), 2.3 (s, 3H), 4.0-4.35 (2q, 4H, J=6 Hz), 4.5-4.75 (m, 1H), 6.7, 6.9 (AB q, 2H, J=15 Hz), 7.33, 7.84 (AB q, 4H, J=9 Hz), 8.25-8.38 (m, 2H), 8.62 (d, 1H, J=2 Hz), 11.5-12.5 (br, 2H); IR (Nujol) 3320, 3150, 1730, 1680, 1630, 1600 cm-1.

Aufarbeitung

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. customThe solvent was evaporated under reduced pressure
  3. customthe residual solid triturated with 50 mL of 1N aqueous sodium carbonate
  4. filtrationThe mixture was filtered
  5. dissolutionthe collected solid dissolved in 20 mL of chloroform
  6. dry with materialThe chloroform solution was dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customThe filtrate was evaporated to dryness
  9. customchromatographed on silica gel
  10. washElution with chloroform:methanol (95:5)

Quellen und Nachweise

ORD-Eintrag
ord-9920b63eb9a44370bfd98499296be83b
Quelldatensatz
uspto-grants-1989_07
Patentnummer
US04845216

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