Patent GB-1328857-A (GB)
Title: Pyrimidine derivatives
IPC: C07C45/00
Filed: 1970-11-09
Abstract: 1328857 Pyrimidin-2(IH)-ones SANDOZ Ltd 9 Nov 1970 [20 Nov 1969 14 May 1970] 53186/70 Heading C2C [Also in Division A5] Novel 1-alkyl-4,6-diphenyl-pyrimidin-2(IH)- ones of the general formula wherein R 1  is a C 1-5  alkyl group and each of R 2  and R 3  is a radical of formula in which each of R 4 <SP>k</SP>, R 5 <SP>k</SP> and R 6 <SP>k</SP> is a hydrogen, fluorine, chlorine or bromine atom or a C 1-3  alkyl, C 1-3  alkoxy, nitro or trifluoromethyl group, provided that no more than one of R 4 <SP>k</SP>, R 5 <SP>k</SP> and R 6 <SP>k</SP> is a nitro, trifluoromethyl, branched alkyl or branched alkoxy group and that when each of R 2  and R 3  is the phenyl radical, R 1  is a C 2-5  alkyl group, are prepared (a) by reaction of a dibenzoylmethane of the general formula R 2 COCH 2 COR 3  with an N-alkylurea of the general formula R 1 NHCONH 2  at 50-150‹ C.; (b) by oxidation of a 1-alkyl-4,6-diphenyl-dihydropyrimidin-2(IH)-one of the general formula wherein either (i) p is a hydrogen atom and q and r together form a second bond betweeen the carbon atoms to which they are attached or (ii) r is a hydrogen atom and p and q together form a second bond between the carbon atoms to which they are attached, and wherein R 2 <SP>1</SP> and R 3 <SP>1</SP> are as R 2  and R 3  except that, when p, q and r are as defined under (ii), neither R 2 <SP>1</SP> nor R 3 <SP>1</SP> is a phenyl radical substituted by a nitro group, in an inert organic solvent; (c) by reaction of a benzoylphenylacetylene of the general formula R 2 C# C-COR 3  with an N-alkylurea of the third general formula above in the presence of a base and in an inert organic solvent; (d) by cyclization of a 1-phenyl-1-alkylamino-2-benzoylethylene of the general formula R 1 NHC(R 2 ) = CHCOR 3  with isocyanic acid in an inert organic solvent; (e) by hydrolysis of a 1-alkyl-4,6- diphenyl-pyrimidin-2(IH)-thione of the general formula at 10-150‹ C.; (f) by oxidation of a 1-alkyl-4,6- diphenyl-dihydropyrimidin-2(IH)-thione of the general formula in an inert organic solvent, and (g) when R 1  is a straight chain C 1-5  alkyl group, by reaction of a 4,6-diphenyl-pyrimidin-2(IH)-one of the general formula or the corresponding tautomeric enol with a compound of the general formula R 1 <SP>1</SP>Z, wherein R 1 <SP>1</SP> is a straight chain C 1-5  alkyl group and Z is a chlorine, bromine or iodine atom or a BO-radical, in which B is a methane-, benzene- or p-toluenesulphonyl group, in the presence of a strong base and in an inert organic solvent which is a C 1-6  alkanol when Z is a halogen atom. Novel 1-alkyl-4,6-diphenyl-dihydropyrimidin- 2(IH)-ones of the fourth general formula above are prepared (h) when p, q and r are as defined under (i) above, by reaction of a 1-phenyl-1- alkylamino-2-benzoyl-ethane of the general formula R 1 NHR 2 CHCH 2 COR 3  with isocyanic acid at up to 35‹ C.; or (i) when p, q and r are as defined under (ii) above, by reaction of a 1-alkyl- 6-phenyl-pyrimidin-2(IH)-one of the general formula wherein R 2 <SP>11</SP> is as R 2 , except that it is not a phenyl radical substituted by a nitro group, with an organometallic compound of the general formula R 3 <SP>11</SP> Q, wherein R 3 <SP>11</SP> is as R 3 , except that it is not a phenyl radical substituted by a nitro group and Q is a lithium atom or -MgX group, in which X is a chlorine or bromine atom, in an inert organic solvent, followed by hydrolysis. Novel 1-alkyl-6-phenyl-pyrimidin-2(IH)-ones of the twelfth general formula above are prepared by reaction of an ethyl 2,4-dioxo-4- phenyl-butyrate of the general formula R 2 <SP>11</SP>- COCH 2 COCOOC 2 H 5  with an N-alkylurea of the third general formula above at 50-180‹ C. in an inert organic solvent and in the presence of an acid catalyst. 1-Phenyl-1-alkylamino-2-benzoyl-ethylenes of the sixth general formula above are prepared by reaction of a benzoylphenylacetylene of the fifth general formula above with an alkylamine of the genral formula R 1 -NH 2 . 1 - Alkyl - 4,6 - diphenyl - pyrimidin - 2(IH)- thiones of the seventh general formula above are prepared by dehydrogenation of a 1-alkyl-4,6- dishenyl-dihydropyrimidin-2(IH)-thione of the eighth general formula above, which is prepared (j) when p, q and r are as under (i) above, by reaction of an N-alkyl-thiourea of the general formula R 1 NHCSNH 2  with a 1-phenyl-2- benzoyl-ethylene of the general formula R 2 CH= CHCOR 2  or (k) when p, q and r are as under (ii) above, by heating a 3-phenyl-3-alkylammoniumpropiophenone isothiocyanate of the general formula (prepared by reaction of a 1-phenyl-1-alkylamino-2-benzoyl-ethane of the eleventh general formula above with isothiocyanic acid in an inert organic solvent).