Organic compounds -- part of the class 532-570 series – Organic compounds – Nitrogen attached directly or indirectly to the purine ring...
Patent
1997-07-17
2000-01-25
Ford, John M.
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitrogen attached directly or indirectly to the purine ring...
C07D23930
Patent
active
060180455
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a process for converting 4,6-dihydroxypyrimidine (1) into 4,6-dichloropyrimidine (2). 4,6-Dichloropyrimidine is useful as a chemical intermediate (for example in the agrochemical industry).
It is known that 4,6-dichloropyrimidine can be prepared by reacting 4,6-dihydroxypyrimidine with phosphorus oxychloride in the presence of a suitable base such as dimethylaniline (see Journal Chemical Society (1943) 574-5, and (1951) 2214) or N,N-dimethylcyclohexylamine (or its hydrochloride) or triethylamine hydrochloride (see GB2287466). It is also known that 4,6-dichloropyrimidine can be prepared by reacting 4,6-dihydroxypyrimidine with phosgene in the presence of a suitable base (see WO 95/29166).
The present invention provides a process for preparing 4,6-dichloropyrimidine comprising treating 4,6-dihydroxypyrimidine with phosphorus oxychloride in the presence of a saturated hindered amine, the hydrochloride salt of a saturated hindered amine, or an unsaturated 5-membered nitrogen containing ring or a mixture thereof, and separating 4,6-dichloropyrimidine from the reaction mixture so formed.
Saturated hindered amines include secondary and tertiary amines, particularly amines of formula R.sup.1 R.sup.2 R.sup.3 N wherein R.sup.1, R.sup.2 and R.sup.3 are, independently, C.sub.1-10 alkyl (especially C.sub.1-6 alkyl) or C.sub.3-6 cycloalkyl or R.sup.1 and R.sup.2 join to form a piperidine or pyrrolidine ring, or R.sup.3 may also be hydrogen. Saturated hindered amines include, for example, N,N-diisopropylethylamine (((CH.sub.3).sub.2 HC).sub.2 (CH.sub.3 CH.sub.2)N, sometimes referred to as Hunig's base, CAS Registry No. 7087-68-5), triethylamine, N,N-diisopropylmethylamine, N,N-diisopropylisobutylamine, N,N-diisopropyl-2-ethylbutylamine, N,N-dicyclohexylmethylamine, N,N-dicyclohexylethylamine, N,N-butylcyclohexylamine, N-methylpyrrolidine or N-ethylpiperidine.
4,6-Dihydroxypyrimidine (1) can also exist in the tautomeric forms (A) and (B) and references to 4,6-dihydroxypyrimidine include all its tautomeric forms.
Unsaturated 5-membered nitrogen containing rings are optionally substituted with C.sub.1-6 alkyl. The ring preferably comprises 1, 2 or 3 nitrogen atoms and is, for example, imidazole, pyrazole, 1,2,3-triazole or 1,2,4-triazole.
In one aspect the present invention provides a process for preparing 4,6-dichloropyrimidine comprising treating 4,6-dihydroxypyrimidine with phosphorus oxychloride in the presence of either a saturated tertiary amine or an unsaturated 5-membered nitrogen containing ring or a mixture thereof.
A saturated tertiary amine is particularly an amine of formula R.sup.1 R.sup.2 R.sup.3 N wherein R.sup.1, R.sup.2 and R.sup.3 are, independently, C.sub.1-10 alkyl (especially C.sub.1-6 alkyl), or R.sup.1 and R.sup.2 join to form a piperidine or pyrrolidine ring. Saturated tertiary amines include, for example, N,N-diisopropylethylamine, triethylamine, N,N-diisopropylmethylamine, N,N-diisopropylisobutylamine, N,N-diisopropyl-2-ethylbutylamine, N,N-dicyclohexylmethylamine, N,N-dicyclohexylethylamine, N-tert-butylcyclohexylamine, N-methylpyrrolidine or N-ethylpiperidine.
Alkyl groups are straight or branched chain and, unless stated otherwise, preferably contain from 1 to 6, especially from 1 to 4, carbon atoms. Examples are methyl, ethyl, iso-propyl, n-propyl, n-butyl, sec-butyl, iso-butyl and tert-butyl.
Cycloalkyl groups comprise 3 to 6 carbon atoms and are optionally substituted by C.sub.1-6 alkyl. Examples are cyclohexyl and 2-ethylcyclohexyl.
In another aspect the present invention provides a process for preparing 4,6-dichloropyrimidine comprising treating 4,6-dihydroxypyrimidine with phosphorus oxychloride in the presence of N,N-diisopropylethylamine or diisopropylethylamine hydrochloride.
In a further aspect the present invention provides a process for preparing 4,6-dichloropyrimidine comprising treating 4,6-dihydroxypyrimidine with phosphorus oxychloride in the presence of N,N-diisopropylethylamine.
Unless specified to the contrary below, it is preferred that the m
REFERENCES:
patent: 3845194 (1974-10-01), Somlo et al.
patent: 4659827 (1987-04-01), Herd et al.
patent: 4668788 (1987-05-01), Beitzke et al.
patent: 5352787 (1994-10-01), Andres et al.
patent: 5525724 (1996-06-01), Hunds
S. Gronowitz, et al., Chemica Scripta, "On the Synthesis of Various Thienyl- and Selenienylpyrimidines", 1986, 26, 305-309.
J. Chem. Soc. (1943), pp. 574-575, "Experiments on the Synthesis of Purine Nucleosides 4,6-Diaminopyrimidine. A New Synthesis of Pyrimidine Derivatives".
The Pyrimidines, by D.J. Brown [1994 Edition], pp 329-340, John Wiley and Sons.
Bull. Chem. Soc. Japan (1973), vol. 46, pp. 299-302, Yanagida et al., "Studies on Nitrile Salts. II. A Facile One-Step Synthesis of the Pyrimidine Nucleus".
Chemical Abstracts, vol. 122, 81393, 1995.
Chemical Abstracts, vol. 113, 115234, 1990.
Chemical Abstracts, vol. 113, 97564, 1990.
Chemical Abstracts, vol. 113, 78321, 1990.
Chemical Abstracts, vol. 113, 23838, 1990.
Chemical Abstracts, vol. 112, 55765, 1990.
Chemical Abstracts, vol. 111, 57357, 1989.
Chemical Abstracts, vol. 110, 172946, 1989.
Chemical Abstracts, vol. 110, 95143, 1989.
Chemical Abstracts, vol. 107, 23647, 1987.
Chemical Abstracts, vol. 107, 58962, 1987.
Chemical Abstracts, vol. 103, 215248, 1985.
Chemical Abstracts, vol. 104, 19434, 1986.
Chemical Abstracts, vol. 106, 196369, 1987.
Chemical Abstracts, vol. 105, 43176, 1986.
Chemical Abstracts, No. 53, No. 21998, 1959.
Derwent Abstracts, No. 92-309033/38, 1992.
Derwent Abstracts, No. 02846X/02, 1976.
F. Ishikawa et al., Cyclic Guanidines. 17. Novel (N-Substituted amino)imidazo[2,1-b]quinazolin-2-ones: Water-Soluble Platelet Aggregation Inhibitors, 28 J. Med. Chem. 1387-93 (1985).
Boyd Ewan Campbell
Jones Raymond Vincent Heavon
Ritchie David John
Whitton Alan John
Ford John M.
LeCroy David P.
Zeneca Limited
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