Formaldehyde → 2-[[4-[(2,4-Diaminopyrido[2,3-d]pyrimidin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid

HRID 370520

Reaktionsgleichung

Reaktionsgleichung von HRID 370520
[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.C=O.[C:35]([BH3-])#N.[Na+]>CS(C)=O.O>[CH3:35][N:19]([C:3]1[CH:2]=[CH:1][C:6]([C:7]([NH:9][CH:10]([C:16]([OH:18])=[O:17])[CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[O:8])=[CH:5][CH:4]=1)[CH2:20][C:21]1[CH:26]=[C:25]2[C:27]([NH2:32])=[N:28][C:29]([NH2:31])=[N:30][C:24]2=[N:23][CH:22]=1

Komponenten

5

Edukt 3

HCID 712FormaldehydeHCID 972725-Deazaaminopterin3×HCID 5003444Sodium cyanoborohydride

Produkt 1

HCID 3353842-[[4-[(2,4-Diaminopyrido[2,3-d]pyrimidin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acidAusbeute 85 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 23503278(Methanesulfinyl)methane--water (1/1)Lösungsmittel

Versuchsvorschrift

Reductive alkylation of diethyl p-aminobenzoyl-L-glutamate) (VI; R=H; R1 =C2H5) with III (Y=CHO) and hydrogen in 70% acetic acid containing Raney nickel gave a 32% yield of 5-deazaaminopterin diethyl ester. Saponification of the ester groups in a mixture of dimethyl sulfoxide-water at ambient temperature gave an 87% yield of 5-deazaaminopterin (II, R=H). Methylation of the latter compound was accomplished by treatment of II (R=H) with formaldehyde and sodium cyanoborohydride in aqueous solution at pH 6.4 to give an 85% yield of 5-deazamethotrexate, (II, R=CH3). The structure of II (R=CH3) was established as described hereinafter in Example 8C by oxidation with alkaline potassium permanganate to give the previously prepared 2-amino-4(3H)oxopyrido[2,3-d]pyrimidine-6-carboxylic acid (VIII), which indicated that methylation had occurred either on the 4- or 10-amino group. Methylation of the 4-amino group was eliminated from consideration by alkaline hydrolysis of the 4-amino group to give 5-deaza-10-methylfolic acid (I, R=CH3).

Quellen und Nachweise

ORD-Eintrag
ord-a017f91985f146f5bdef6ad6a0e4f621
Quelldatensatz
uspto-grants-1985_07
Patentnummer
US04526964

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