Studies directed toward a total synthesis of nucleoside Q. Annulation of 2,6-diaminopyrimidin-4-one with .alpha.-halo carbonyls to form pyrrolo[2,3-d]pyrimidines and furo[2,3-d]pyrimidines

Abstract

The condensation of 2,6-diaminopyrimidin-4-one (3) with various a-halo carbonyl compounds is examined. The reaction produces two types of products, both regiospecifically. For example, treatment of 3 with a-chloroacetone affords 2-amino-6-methylpyrrolo [2,3-d]pyrimidin-4-one (5a) and 2,4-diamino-5-methylfuro[2,3-d]pyrimidine (6a). Depending upon the nature of the -halo carbonyl compound, pyrrolo [2,3-d]pyrimidin-4-one and/or furo[2,3djpyrimidine products were observed. Structural assignments were based on UV, NMR, and 13C NMR. 2-Chloropropionaldehyde was found to react with 3 to produce 2-amino-5-methylpyrrolo[2,3-d]pyrimidin-4-one (7) exclusively, thus providing an entry into the substitution pattern of nucleoside Q (2).The pyrrolo[2,3-d]pyrimidine ring system has aroused considerable interest due to its presence in several natural products. It is contained in the nucleoside antibiotics tubercidin (la), toyocamycin (lb), and sangivamycin (lc),2 as well as in the more recently characterized hypermodified nucleosides Q (2a)3 and Q* (2b and 2c).4 Both Q and Q* are present in the initial position of the anticodon in tyrosine, aspartate, asparagine, and histidine tRNA from various organisms.5

Synthesis of 5-amino-1,3,4-thiadiazole-2-sulphonamide derivatives and their inhibition effects on human carbonic anhydrase isozymes

“…Compound 18 was produced in 84% yield by reaction of compound 7 with chloroacetone in DMF at 60°C for 72 h [42]. Syntheses of compounds 8-18 from compound 7 are shown in Scheme 2.…”

Synthesis and evaluation of a classical 2,4-diamino-5-substituted-furo[2,3-d]pyrimidine and a 2-amino-4-oxo-6-substituted-pyrrolo[2,3-d]pyrimidine as antifolates

“…19 For the synthesis of the α-halo ketone 21 from the corresponding α-diazomethane, 20 the corresponding [4-(methoxycarbonyl)phenyl]acetic acid 18 was required. The literature provides several methods for the synthesis of 18.…”

“…Drug preparation-Drug solutions were standardized using extinction coefficients. Extinction coefficients were determined for 13 (pH 1, λ max 227 nm (22,900); pH 7, λ max 255 nm (19,200); pH 13, λ max 248 nm (19,300)) and for 14 (pH 1, λ max−1 248 nm (20,300), λ max−2 301 nm (7,900); pH 7, λ max 247 nm (20,400); pH 13, λ max 248 nm (20,200)) and the extinction coefficients for methotrexate (MTX), a gift of Immunex (Seattle, WA), were from the literature. 30 Aminopterin was purchased from Sigma Chemical Co. (St. Louis, MO).…”

Convenient Selective Synthesis of Substituted Pyrido[2,3-d]pyrimidones and Annulated Derivatives

“…The precipitate formed was collected by filtration, and then purified by crystallization from an appropriate solvent to give compound 12 and 16, respectively. [4,5-b] -5,5a,6,7,8,9-hexahydro-1,3-dimethyl-5-phenylpyrimido [4,5-b] (18) A mixture of 6-amino-1,3-dimethyl-uracil (1) (1 g, 6.5 mmol), 3-cinnamoyl-1-phenyl-2,4(1H, 3H)-quinolinedione (2.4 g, 6.5 mmol) in glacial acetic acid (20 mL) was heated for 1 h on a steam bath, kept overnight at r. t., diluted with water, and then basified with ammonia. The precipitate formed was collected by filtration, and then purified by crystallization from acetic acid to give 18.…”