New synthesis of 6,7-dihydro[1,3]thiazolo[2,3-f]purine-2,4(1H,3H)-diones

Abstract

SHORT COMMUNICATIONSSeveral methods of synthesis of 6,7-dihydro[1,3]-thiazolo[2,3-f]purine-2,4(1H,3H)-diones have been reported, e.g., from 8-brom-7-(2-haloethyl)-3,7-dihydro-1H-purine-2,6-diones and sodium sulfide [1], by reaction of 8-halo-7-(thiiran-2-ylmethyl)-3,7-dihydro-1H-purin-2,6-diones with nucleophilic reagents [2], etc. We now propose a new one-step procedure for the preparation of 6,7-dihydro[1,3]thiazolo[2,3-f]purin-2,4(1H,3H)-dione derivatives via reaction of 8-halo-3,7-dihydro-1H-purine-2,6-diones with thiiranes. The reactions were carried out in DMF with 8-halo-3,7-dihydro-1H-purine-2,6-diones Ia-Ic as free bases (in the presence of a base) or potassium salts and an equimolar amount of thiirane IIa-IIc. 6,7-Dihydro[1,3]-thiazolo[2,3-f]purine-2,4(1H,3H)-diones IIIa-IIIc were thus obtained in 59-68% yield.The structure of compounds IIIa-IIIc was confirmed by elemental analyses and 1 H and 13 C NMR spectra. The properties of compound IIIa were consistent with published data [1]. Substituted thiiranes IIb and IIc gave rise to 7-substituted dihydrothiazolopurines IIIb and IIIc whose structure was additionally proved by independent synthesis of compound IIIb from 8-bromo-1,3-dimethyl-7-(thiiran-2-ylmethyl)-3,7-dihydro-1H-purine-2,6-dione and diethylamine [2]. Samples of IIIb prepared by the two methods showed no depression of the melting point on mixing, and their 1 H NMR spectra were fully identical. Our results indicated that opening of the thiirane ring follows the Krasuskii rule [3]. 1,3-Dimethyl-6,7-dihydro[1,3]thiazolo[2,3-f]-purine-2,4(1H,3H)-dione (IIIa).A solution of 2.59 g (10 mmol) of purine Ia, 0.56 g (10 mmol) of potassium hydroxide, and 0.60 g (10 mol) of thiirane IIa in 40 ml of DMF was heated for 3 h at 45-50°C. The mixture was cooled, and the precipitate was filtered off and washed with water. Yield 1.40 g (59%), mp 259-260°C (from i-BuOH) [1]. 1 H NMR spectrum, δ, ppm: 3.38 s (3H, 3-CH 3 ), 3.54 s (3H, 1-CH 3 ), 3.88-4.00 m (2H, SCH 2 ), 4.42-4.53 m (2H, NCH 2 ). Found, %: C 45.56; H 4.33; N 23.18. C 14 H 21 N 5 O 2 S. Calculated, %: C 45.37; H 4.23; N 23.51.7-(Diethylaminomethyl)-1,3-dimethyl-6,7-dihydro[1,3]thiazolo[2,3-f]purine-2,4(1H,3H)-dione (IIIb). A solution of 1.49 g (5 mmol) of purine Ib potassium salt and 0.73 g (5 mmol) of thiirane IIb in 30 ml of DMF was heated for 1 h under reflux. The mixture was cooled and diluted with water until a solid separated. The precipitate was filtered off and washed with water. Yield 1.10 g (68%), mp 177-178°C (from EtOH). 1 H NMR spectrum, δ, ppm: 0.99 t (6H, CH 2 CH 3 , 3 J = 7.1 Hz), 2.55 q (4H, NCH 2 CH 3 , 3 J = I, R = Me, Hlg = Br, X = H (a), K (b); R = H, Hlg = Cl, X = K (c); II, R′ = H (a), Et 2 NCH 2 (b), MeOCH 2 (c); III, R = Me, R′ = H (a), Et 2 NCH 2 (b); R = H, R′ = MeOCH 2 (c).