Methods and intermediates for preparing therapeutic compounds
The present disclosure relates to methods and intermediates useful for preparing a compound of formula I: or a co-crystal, solvate, salt or combination thereof.
1. A process for preparing a compound of formula V-03-A:
or a co-crystal, solvate, salt, or combination thereof, comprising:
(a) combining a compound of formula V:
or a co-crystal, solvate, salt, or combination thereof, wherein R is B(OH) 2 , B(OCH(Me)CH 2 C(Me) 2 O), B((1,2-di-O)C 6 H 4 ), B(OCH 2 C(Me) 2 CH 2 O), BF 3 K, B(O 2 CCH 2 N(Me)CH 2 CO 2 ), or B(OC(Me) 2 C(Me) 2 O), with a mesylating reagent, a base and a solvent to provide a compound of V-04-A:
or a co-crystal, solvate, salt, or combination thereof; and
(b) hydrolyzing the compound of formula V-04-A or a co-crystal, solvate, salt, or combination thereof, with a nucleophilic reagent, a solvent, and optionally, a phase transfer catalyst to provide the compound of formula V-03-A or a co-crystal, solvate, salt, or combination thereof.
2. The process of claim 1 , wherein R is B(OC(Me) 2 C(Me) 2 O).
3. The process of claim 1 , wherein the mesylating reagent used in step (a) is methanesulfonic anhydride or methanesulfonyl chloride.
4. The process of claim 1 , wherein the base used in step (a) is selected from the group consisting of triethylamine, N-methylmorpholine, tri-n-propylamine, ethyl diisopropylamine, tri-n-butylamine, pyridine, 2,6-lutidine, collidine, sodium bicarbonate, sodium carbonate, sodium phosphate monobasic, sodium phosphate dibasic, potassium bicarbonate, potassium carbonate, potassium phosphate monobasic, potassium phosphate dibasic, sodium tert-amylate, and sodium tert-butoxide.
5. The process of claim 1 , wherein the base used in step (a) is triethylamine.
6. The process claim 1 , wherein the solvent used in step (a) is selected from the group consisting of diethyl ether, 1,4-dioxane, 2-methyltetrahydrofuran, dimethoxyethane, toluene, xylenes, isopropyl acetate, isobutyl acetate, dichloromethane, acetonitrile, and a combination thereof.
7. The process of claim 1 , wherein the solvent used in step (a) is 2-methyltetrahydrofuran.
8. The process of claim 1 , wherein step (a) is carried out in the temperature range of from about −20° C. to about 100° C.
9. The process of claim 1 , wherein the nucleophilic reagent used in step (b) is selected from the group consisting of sodium hydroxide, lithium hydroxide, potassium hydroxide, sodium ethanethiolate, N-acetylcysteine, sodium thiophenolate, choline, sodium methoxide, sodium ethoxide, potassium ethoxide, sodium n-propoxide, sodium i-propoxide, sodium t-butoxide, methylamine, ethylamine, n-propylamine, dimethylamine, diethylamine, and hydroxylamine.
10. The process of claim 1 , wherein the nucleophilic reagent used in step (b) is sodium hydroxide.
11. The process of claim 1 , wherein the solvent used in step (b) is selected from the group consisting of diethyl ether, 1,4-dioxane, 2-methyltetrahydrofuran, dimethoxyethane, toluene, xylenes, isopropyl acetate, isobutyl acetate, dichloromethane, acetonitrile, N,N-dimethylformamide, N-methyl-2-pyrrolidone, N,N-dimethylacetamide, and a combination thereof.
12. The process of claim 1 , wherein solvent used in step (b) is 2-methyltetrahydrofuran and water.
13. The process of claim 1 , wherein the phase transfer catalyst used in step (b) is selected from the group consisting of tetrabutylammonium hydrogen sulfate, tetrabutylammonium chloride, benzyltributylammonium bromide, 1-methylimidazolium hydrogen sulfate, and tetrabutylphosphonium chloride.
14. The process of claim 1 , wherein the phase transfer catalyst used in step (b) is tetrabutylammonium hydrogen sulfate.
15. The process of claim 1 , wherein step (b) is carried out in the temperature range of from about −20° C. to about 100° C.