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US 2009/0023919 A1Published application
Synthesis of temozolomide and analogs
AssigneeSchering Corporation
InventorsShen-Chun Kuo, Janet L. Mas, Donald Hou
Life of this patent
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Abstract
This invention relates to a novel process for the synthesis of Temozolomide, an antitumor compound, and analogs, and to intermediates useful in this novel process.
Claims9
A compound of Formula IV:
- Pg″N.CO.C(:NOH).CN;
- Formula V:
- Pg″N.CO.CH(NH2).CN;
- or Formula VI:
- Pg″N.CO.CH(N:Ar).CN, or a salt thereof,
- wherein:
- Pg″ is:
- (i) a divalent protecting group that is readily removable by hydrolysis or hydrogenolysis;
- (ii) two monovalent protecting groups designated (Pg) that are readily removable by hydrolysis or hydrogenolysis;
- or (iii) a hydrogen atom together with a bulky monovalent protecting group (Pg) that is readily removable by hydrolysis or hydrogenolysis;
- and
- Ar is an arylmethylene group, and wherein the phrase “readily removable by hydrolysis or hydrogenolysis” refers to a divalent protecting group;
- a pair of two monovalent protecting groups or hydrogen together with a bulky protecting group which can be removed by hydrogenolysis or hydrolysis when the compound of Formulae IV, V, or VI has been incorporated into a compound of Formula III, or a salt thereof,
- wherein “R” in Formula III is an alkyl group having from 1 to 6 carbon atoms.
11 more elements
An acid addition salt of a compound of the formulae 4, 5, 6, or 17
A salt of the compound of the formula 13 formed by treatment of the compound with a base.
A process for the preparation of a compound of the Formula 17a,
- Formula 17a, or an acid addition salt thereof, the process comprising:
- (i) condensing the compound of Formula 14,
- (H2N.CO.CH(NH2).CN) Formula 14,
- with a compound of Formula 7a,
- R.NH.CO.NH.CH:N.CO.NH.R Formula 7a,
- in an inert organic solvent;
- or condensing the compound of Formula 14,
- (H2N.CO.CH(NH2).CN) Formula 14,
- with an N—R-urea and an orthoformate in an inert organic solvent, wherein “R” an alkyl group having from 1 to 6 carbon atoms;
- and
- (ii) hydrolyzing the resulting compound of the Formula II
- and isolating the resulting compound of the Formula 17a or an acid addition salt thereof.
9 more elements
A process for the preparation of a compound of the Formula II,
- wherein R is an alkyl group having from 1 to 6 carbon atoms, the process comprising:
- (i) condensing the compound of Formula 14,
- (H2N.CO.CH(NH2).CN) Formula 14,
- with a compound of Formula 7a,
- R.NH.CO.NH.CH:N.CO.NH.R Formula 7a,
- wherein “R” is as defined above, in an inert organic solvent;
- or
- (ii) condensing the compound of Formula 14,
- (H2N.CO.CH(NH2).CN) Formula 14,
- with an N—R-urea and an orthoformate, wherein “R” is as defined above, in an inert organic solvent.
7 more elements
Dependencies are inferred from the claim text.