Protease inhibitor precursor synthesis
View Patent ↗The present invention provides a compound having the structure (I) and processes for the production thereof and the intermediates used in such process.
1. A compound having the formula (I) or a stereoisomer thereof,
or a salt form thereof.
2. A compound according to claim 1 wherein the compound is one of the following stereoisomers
3. A process for the production of a compound as described in claim 1 comprising submitting a compound having the formula (II)
wherein
X and Y are independently selected from Si and C; and,
R 1 , R 2 , R 3 and R 4 are independently selected from the group consisting of —H and monovalent hydrocarbon radicals;
R 1 and R 2 can be taken together to form a bivalent hydrocarbon radical represented by —R 1 —R 2 —;
R 3 and R 4 can be taken together to form a bivalent hydrocarbon radical represented by —R 3 —R 4 —;
to alcohol deprotection conditions and submitting the thus formed deprotected intermediate to an intramolecular cyclisation to obtain a compound of formula (I).
4. A process as described in claim 3 further comprising oxidising a compound having the formula (III)
wherein
X and Y are independently selected from Si and C; and,
R 1 , R 2 , R 3 and R 4 are independently selected from the group consisting of —H and monovalent hydrocarbon radicals;
R 1 and R 2 can be taken together to form a bivalent hydrocarbon radical represented by —R 1 —R 2 —;
R 3 and R 4 can be taken together to form a bivalent hydrocarbon radical represented by —R 3 —R 4 —;
to obtain a compound of formula (II).
5. A process as described in claim 4 further comprising hydroborating a compound having the formula (IV)
wherein
X and Y are independently selected from Si and C; and,
R 1 , R 2 , R 3 and R 4 are independently selected from the group consisting of —H and monovalent hydrocarbon radicals;
R 1 and R 2 can be taken together to form a bivalent hydrocarbon radical represented by —R 1 —R 2 —;
R 3 and R 4 can be taken together to form a bivalent hydrocarbon radical represented by —R 3 —R 4 —;
and subsequently oxidising the thus formed hydroborated intermediate to obtain a compound of formula (III).
6. A process according to claim 3 , wherein the deprotecting agent is selected from the group consisting of hydrogenolysis reagents, fluoride reagents, acids and bases, preferably, inorganic and organic acids, most preferably sulfonic acids or carboxylic acids.
7. A process according to claim 3 , wherein deprotection takes place in an aqueous solution, optionally comprising one or more organic solvents.
8. A process according to claim 4 , wherein the oxidation is carried out using Swern, Pfitzner-Moffatt or Parikh-Doering conditions.
9. A process for the production of a compound as described in claim 2 comprising submitting a compound having the formula (II)
wherein
X and Y are independently selected from Si and C; and,
R 1 , R 2 , R 3 and R 4 are independently selected from the group consisting of —H and monovalent hydrocarbon radicals;
R 1 and R 2 can be taken together to form a bivalent hydrocarbon radical represented by —R 1 —R 2 —;
R 3 and R 4 can be taken together to form a bivalent hydrocarbon radical represented by —R 3 —R 4 —;
to alcohol deprotection conditions and submitting the thus formed deprotected intermediate to an intramolecular cyclisation to obtain a compound of formula (I).
10. A process as described in claim 9 further comprising oxidising a compound having the formula (III)
wherein
X and Y are independently selected from Si and C; and,
R 1 , R 2 , R 3 and R 4 are independently selected from the group consisting of —H and monovalent hydrocarbon radicals;
R 1 and R 2 can be taken together to form a bivalent hydrocarbon radical represented by —R 1 —R 2 —;
R 3 and R 4 can be taken together to form a bivalent hydrocarbon radical represented by —R 3 —R 4 —;
to obtain a compound of formula (II).
11. A process as described in claim 10 further comprising hydroborating a compound having the formula (IV)
wherein
X and Y are independently selected from Si and C; and, R 1 , R 2 , R 3 and R 4 are independently selected from the group consisting of —H and monovalent hydrocarbon radicals;
R 1 and R 2 can be taken together to form a bivalent hydrocarbon radical represented by —R 1 —R 2 —;
R 3 and R 4 can be taken together to form a bivalent hydrocarbon radical represented by —R 3 —R 4 —;
and subsequently oxidising the thus formed hydroborated intermediate to obtain a compound of formula (III).