Methods for preparing 2-alkynyladenosine derivatives
AssigneeBristol-Myers Squibb Pharma Company
InventorsIain Pickersgill, Edward Cheesman
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Abstract
Disclosed are methods for preparing 2-alkynyladenosine derivatives of formula A: or a stereoisomer, pharmaceutically acceptable salt, hydrate, solvate, acid salt hydrate or isomorphic crystalline form thereof, the method comprising the step of: contacting 2-iodoadenosine-5′-N-ethyluronamide with a compound of formula B: wherein Z is —C(═O)OR or —CH2OC(═O)R, where R is a C1 to C5 alkyl, preferably methyl. The methods are useful for preparing 2-alkynyladenosine derivatives that are, in certain embodiments, adenosine receptor agonists.
Claims27
A method for preparing a compound of formula A:
- or a stereoisomer, pharmaceutically acceptable salt, hydrate, solvate, acid salt hydrate or isomorphic crystalline form thereof, the method comprising the step of:
- contacting 2-iodoadenosine-5′-N-ethyluronamide with a compound of formula B:
- wherein Z is —C(═O)OR or —CH2OC(═O)R, where R is a C1 to C5 alkyl.
A method for preparing 2-iodoadenosine-5′-N-ethyluronamide, comprising the steps of:
- providing 2-iodoadenosine;
- protecting the hydroxyl groups of said 2-iodoadenosine with an acetonide group;
- oxidizing the primary alcohol of said acetonide-protected 2-iodoadenosine to an acid derivative of said acetonide-protected 2-iodoadenosine;
- converting said acid derivative to an N-ethylamide derivative of said acetonide-protected 2-iodoadenosine;
- and
- deprotecting said N-ethylamide of said acetonide-protected 2-iodoadenosine to form said 2-iodoadenosine-5′-N-ethyluronamide.
A method for preparing a compound of formula B:
- wherein Z is —CH2OC(═O)R, where R is a C1 to C5 alkyl, comprising the steps of.
- providing 1,4-methanol cyclohexane;
- and
- preparing a mono-tosyl derivative of said 1,4-methanol cyclohexane;
- preparing an acetylide-substituted compound of the formula:
- from said mono-tosyl derivative of said 1,4-methanol cyclohexane;
- and
- converting said acetylide-substituted compound to a compound of formula B:
A method for preparing a compound of formula B:
- wherein Z is —C(═O)OR, where R is a C1 to C5 alkyl, comprising the steps of.
- providing 1,4-methanol cyclohexane;
- preparing a mono-tosyl derivative of said 1,4-methanol cyclohexane;
- preparing an acetylide-substituted compound of the formula:
- from said mono-tosyl derivative of said 1,4-methanol cyclohexane;
- oxidizing said acetylide-substituted compound using radical oxidation;
- and
- esterifying said product of said oxidation to a compound of formula B:
Dependencies are inferred from the claim text.