Hydrochloric Acid → N-[4-[[(2,4-Diaminopyrido[2,3-d]pyrimidin-6-yl)methyl]methylamino]benzoyl]-L-glutamic acid

HRID 370524

Reaktionsgleichung

Reaktionsgleichung von HRID 370524
[CH:1]1[C:6]([C:7]([NH:9][C@H:10]([C:16]([OH:18])=[O:17])[CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[O:8])=[CH:5][CH:4]=[C:3]([NH:19][CH2:20][C:21]2[CH:26]=[C:25]3[C:27]([NH2:32])=[N:28][C:29]([NH2:31])=[N:30][C:24]3=[N:23][CH:22]=2)[CH:2]=1.[OH-].[Na+].C=O.[BH3-][C:38]#N.[Na+].Cl>O=O>[NH2:31][C:29]1[N:28]=[C:27]([NH2:32])[C:25]2[CH:26]=[C:21]([CH2:20][N:19]([CH3:38])[C:3]3[CH:2]=[CH:1][C:6]([C:7]([NH:9][C@H:10]([C:16]([OH:18])=[O:17])[CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[O:8])=[CH:5][CH:4]=3)[CH:22]=[N:23][C:24]=2[N:30]=1

Komponenten

7

Edukt 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 972725-DeazaaminopterinHCID 5003444Sodium cyanoborohydride

Produkt 1

HCID 12908480N-[4-[[(2,4-Diaminopyrido[2,3-d]pyrimidin-6-yl)methyl]methylamino]benzoyl]-L-glutamic acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 977OxygenLösungsmittel

Versuchsvorschrift

A suspension of Compound II (R=H) (100 mg, 0.211 mmol) in O2 free water (5 ml) under N2 was adjusted to pH 6.4 with 1N NaOH to give a solution which was treated with 38% HCHO (83.1 μl, 1.14 mmol) followed by NaBH3CN (19.9 mg, 0.317 mmol). The solution was maintained at pH 6.4 by gradual addition of 1N HCl over a period of 45 minutes. The solution was stirred under N2 for 23 hours, filtered and acidified to pH 3.6 with 1N HCl. The product was collected by filtration, washed with water at pH 3.6 and dried in vacuo (P2O5): yield 97 mg (94%), mp indefinite (softens and darkens above 217° C.); mass spectrum, m/e 454 (M+1)+ ; λmax nm (ε×10-3): 0.1N HCl-221 (37.1), 311 (19.0); pH 7-219 (35.1), 247 (18.1), 305 (25.2); 0.1N NaOH-249 (19.9), 305 (25.0), 355 sh (6.15; 1H-NMR (DMSO-d6, <5% w/v), δ2.00 m (CH2CH2CO), 2.28 t (CH2CO), 3.12 s (CH3), 4.32 m (CHN), 4.66 s (CH2N), 6.78 d, 7.72 d (C6H4), 8.31 d (5-CH), 8.59 d (7-CH).

Aufarbeitung

  1. customto give a solution which
  2. filtrationfiltered
  3. filtrationThe product was collected by filtration
  4. washwashed with water at pH 3.6
  5. dry with materialdried in vacuo (P2O5)
  6. customyield 97 mg (94%), mp indefinite (softens and darkens above 217° C.)
  7. wait1H-NMR (DMSO-d6, <5% w/v), δ2.00 m (CH2CH2CO), 2.28 t (CH2CO), 3.12 s (CH3), 4.32 m (CHN), 4.66 s (CH2N), 6.78 d, 7.72 d
  8. custom(C6H4), 8.31 d (5-CH), 8.59 d (7-CH)

Quellen und Nachweise

ORD-Eintrag
ord-ecc27af279ea41e9bc7154d6d271890f
Quelldatensatz
uspto-grants-1985_07
Patentnummer
US04526964

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