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During an investigation of the factors affecting the reaction of 2′,3′-O-isopropylidene nucleosides with phosphoryl chloride, trialkyl phosphates were found to be powerful accelerators and useful solvents for the phosphorylation. The addition of a trialkyl phosphate to a large excess of phosphoryl chloride was markedly effective in promoting the phosphorylation; further, the lower alkyl phosphates, such as trimethyl and triethyl phosphates, were able to replace the excessive amount of phosphoryl chloride as solvents. When unprotected nucleosides were treated with phosphoryl chloride in trimethyl phosphate, the corresponding 5′-phosphates were mainly produced, together with a small amount of highly-phosphorylated products, in good yields. On the contrary, the treatment of 5′-O-acetyl nucleosides in a similar manner gave the corresponding 2′(or 3′)-nucleotides in low yields. The formation of the 2′(or 3′)-phosphate was strongly inhibited by the addition of a small amount of water to the reaction mixture. Thus, the selective phosphorylation of unprotected nucleosides to the 5′-nucleotides in a one-step procedure was accomplished.

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NOTESVOL, 32 B. Methyl Ester 4b.-By a procedure similar to that used on 4a, the methyl ester 4b was obtained in 72% yield upon treatment of the anhydride with methanol, mp 117-118', [ C Y ]~D +3.2", [(Y]"236 +1240° (c 0.63, methanol). Anal. Calcd for ClaH2lNzSClOr (348.9): C, 48.20; H, 6.07; N, 8.03; S, 9.19. Found: C,48.23; H , 6.23; N, 8.16; S, 9.13.C . Methyl Ester 4b from Nw-Benzyloxycarbonyl-S-2-aminoethyl-L-cysteine.-Twelve grams of N'-benzyloxycarbonyl-S-2aminoethyl-L-cysteiae (0.04 mole), prepared according to the procedure of Lindley6 (mp 212-213'), was esterified in 90 ml of anhydrous methanol plus 60 ml of 2.5 N methanolic HCl a t room temperature overnight. After removing the solvent under vacuum, the product was crystallized from acetone with ether. The crystallized compound weighed 13 g (93y0), mp 117'. Na-Benzoyl-Nu-benzyloxycarbonyl-S-2-aminoethyl-L-cysteine Ethyl or Methyl Ester ( 5 ) . A . Ethyl Ester 5a.-The hydrochloride (4a, 7.4 g, 0.0204 mole) was suspended in a mixture of ethyl acetate (100 ml) and ether (100 ml). A solution of 3.1 g of KzCO~ (0.0225 mole) in 180 ml of water was added with stirring. The organic layer containing the free base was separated and treated with 2.8 ml (0.024 mole) of benzoyl chloride and a solution of K z C O~ in water (2.9 g in 120 ml) with stirring for 30 min. Several drops of pyridine were added. The product in the organic layer was washed with 0.1 N HC1, 27, KHCOI, and water. After the organic layer had been dried over anhydrous Na2SO4, the solvent was removed under vacuum. The product was crystallized from acetone with petroleum ether to yield 4.62 g (53yo), mp 94-96', [a]"D -37.8' ( c 1, ethanol). Anal. Calcd for CZZHZ~NZSO~ (430.5): C, 61.37; H , 6.09; Registry No.-l,Although a number of papers have been reported on the synthesis of purines from imidazole derivatives, there are few reports2 in which purines were prepared by the ring closure of the pyrimidine starting from (1) This paper has been presented a t the 86th Annual Meeting of the (2) E. Shaw, J . Bid. Chem., 185, 439 (1950).

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