Synthesis of Some 2,5-Diamino-4-n-butylamino-6-substituted Pyrimidines<sup>1</sup>

Pl, Warner; Tj, Bardos

doi:10.1021/jm00324a053

Cited by 4 publications

(1 citation statement)

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“…of the analytically pure product, which darkened at-230°a nd decomposed at ca. 240°: !,'"( (c) 500 sh mg (10,300). 482 (11,400), 378 11.800), 340 sh <6300), 279 38,100).…”

Section: Experimental Section21'mentioning

confidence: 99%

Synthesis of 6-(N-alkyl-N-arylamino)pyrimidines as potential antimetabolites

Warner¹,

Bardos²

1970

J. Med. Chem.

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Thirty-eight new 6-(AT-alkyl-Ar-arylamino)pyrimidines were prepared as open-chain analogs of riboflavin that lack the Ni" atom of the central ring. Most of these compounds were prepared by simple coupling reaction between the appropriate 2,4-disubstituted 6-chloropyrimidine and an Ar-alkylamline, usually under fusion conditions, except in the case of the 5-N02 derivatives where Cl was sufficiently activated to react in refluxing EtOH, Et3N, or DMF. Several of the compounds showed in vitro activity against Sarcoma 180 cells, 2,4-diamino-6-(AT-ethy 1-3,4-dime thylanilino)pyrimidine•HCl (34) being the most active.2,4-Diamino-6,7-dimethyl-2,4-dideoxyalloxazine (I) has been found to antagonize both riboflavin (II) and folinic acid in several microbiological test systems5•6 and to inhibit the growth of transplanted tumors in mice.7,8 However, the poor tissue absorption properties of I limited further in vivo studies with this compound. It was felt that introduction of various alkyl and hydroxyalkyl chains in the X9 position of I might lead to compounds with increased solubility and better absorption properties.9 Such compounds would also bear a greater structural resemblance to II. However, direct alkylation of I resulted in substitution in the Ni position,9 and our attempts to react dimeric 4,5dimethyl-o-benzoquinone6 with a variety of 4-substit-uted 6-alkylammo-2,5-diaminopyrimidines10 led to condensation products which were difficult to purify.Cheng, O'Brien, and coworkers reported the antitumor activities of various 5-nitro-(and 5-nitroso)-2,4-diamino-6-arylaminopyrimidines, and noted the structural resemblance of 6-arylaminopyrimidines to ribo-(1) This research was supported by Grant No. CA 06695-7 from the Na-

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“…of the analytically pure product, which darkened at-230°a nd decomposed at ca. 240°: !,'"( (c) 500 sh mg (10,300). 482 (11,400), 378 11.800), 340 sh <6300), 279 38,100).…”

Section: Experimental Section21'mentioning

confidence: 99%