Patent ID: 11884688
Assignee: TAE LIFE SCIENCES, LLC
Field: Pharmaceuticals (Chemistry)
Classification: CPC A  C | IPC C

Claim 0:
1. A composition produced by a method of conversion of L-tyrosine to a target material, comprising:
(i) Conversion of N-Boc-Tyr(3-Br, 4-MeO)—OMe (4) to the aryl boronic acid N-Boc-Tyr(3-B(OH)2-4-MeO)—OMe (5) which comprises a palladation followed by a metal exchange to the required boronic acid comprising the following:
a. a solvent mixture comprising methanol and dimethoxyethane;
b. a ligand substituent comprising potassium acetate;
c. a reagent of type aryl bromide comprising N-Boc-Tyr(3-Br, 4-MeO)—OMe (4);
d. a boronating agent comprising tetrahydroxyborane;
e. a palladium catalyst comprising chloro((tir-tert-butylphosphine)-2-(2-aminobiphenyl))palladium (II); and
f. a purification comprising (i) quenching with water, (ii) a solvent exchange comprising ethyl acetate, and (iii) a flash chromatography on silica with approximately 25% ethyl acetate in hexanes;

(ii) Following the introduction of boronic acid, the synthesis diverges to form the compounds BTS (7) and BTS(OMe) (9);
(iii) Conversion N-Boc-Tyr(3-B(OH)2-4-MeO)—OH (8) to reveal the structure of BTS(OMe) (9) comprising:
a. a solution comprising 4 M hydrochloric acid in dioxane;
b. a reagent of type tertbutylcarbamate comprising, N-Boc-Tyr(3-B(OH)2, 4-OMe)-OH; and
c. a purification comprising a reverse phase chromatography with a range of 0% to 20% acetonitrile in water;

(iv) Conversion of N-Boc-Tyr(3-B(OH)2, 4-MeO)—OMe (5) to BTS (7) which comprises a simultaneous methyl ether cleavage and carbamate removal subsequently, followed by saponification comprising:
a. a solution comprising dichloromethane;
b. an added reagent comprising N-Boc-Tyr(3-B(OH)2, 4-MeO)—OMe (5);
c. a reactant comprising boron tribromide;
d. a solvent exchange from dichloromethane to water;
e. a reactant comprising LiOH; and
f. a purification comprising a reverse phase chromatography with a range of 0% to 20% acetonitrile in water.