Patent ID: 11919905
Assignee: HANGZHOU ADAMERCK PHARMLABS, INC.
Field: Organic fine chemistry (Chemistry)
Classification: CPC C  A  Y | IPC A  C

Claim 9:
10. A process for preparing a compound of the following formula 1 according to claim 1:, wherein:
R is F, Cl, Br, NO2, C1-C6 alkyl, CF3, or OCH3;
R1 is F, Cl, Br, NO2, C1-C6 alkyl, CF3, or OCH3;
R2 is, R3 is C1-C6 alkyl; and
HX is a pharmaceutically acceptable inorganic acid or a pharmaceutically acceptable organic acid selected from the group consisting of hydrofluoric acid, hydrochloric acid, hydrobromic acid, nitric acid, phosphoric acid, sulfuric acid, formic acid, acetic acid, trifluoroacetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, picric acid, benzoic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and naphthalenesulfonic acid;

wherein the process comprises the following steps:
(1) reacting a compound of the following formula 2:, wherein:
R is F, Cl, Br, NO2, C1-C6 alkyl, CF3, or OCH3;
R1 is F, Cl, Br, NO2, C1-C6 alkyl, CF3, or OCH3; and
R2 is, with a compound of the following formula 3:, wherein:
R3 is C1-C6 alkyl;

in the presence of dicyclohexyl carbodiimide (DCC), to provide a compound of the following formula 4:, wherein:
R is F, Cl, Br, NO2, C1-C6 alkyl, CF3, or OCH3;
R1 is F, Cl, Br, NO2, C1-C6 alkyl, CF3, or OCH3;
R2 is, and
R3 is C1-C6 alkyl;

(2) reacting the compound of the formula 4 above with an acid of the following formula 5:

HX   5

wherein:
HX is a pharmaceutically acceptable inorganic acid or a pharmaceutically acceptable organic acid selected from the group consisting of hydrofluoric acid, hydrochloric acid, hydrobromic acid, nitric acid, phosphoric acid, sulfuric acid, formic acid, acetic acid, trifluoroacetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, picric acid, benzoic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and naphthalenesulfonic acid;

to provide a compound of the following formula 6:, wherein:
R is F, Cl, Br, NO2, C1-C6 alkyl, CF3, or OCH3;
R1 is F, Cl, Br, NO2, C1-C6 alkyl, CF3, or OCH3;
R2 is, R3 is C1-C6 alkyl; and
HX is a pharmaceutically acceptable inorganic acid or a pharmaceutically acceptable organic acid selected from the group consisting of hydrofluoric acid, hydrochloric acid, hydrobromic acid, nitric acid, phosphoric acid, sulfuric acid, formic acid, acetic acid, trifluoroacetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, picric acid, benzoic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and naphthalenesulfonic acid;

(3) reacting the compound of the formula 6 above with sodium bicarbonate (NaHCO3), to provide a compound of the following formula 7:, wherein:
R is F, Cl, Br, NO2, C1-C6 alkyl, CF3, or OCH3;
R1 is F, Cl, Br, NO2, C1-C6 alkyl, CF3, or OCH3;
R2 is, and
R3 is C1-C6 alkyl;

(4) reacting the compound of the formula 7 above with a compound of the following formula 8:, to provide a compound of the following formula 9:, wherein:
R is F, Cl, Br, NO2, C1-C6 alkyl, CF3, or OCH3;
R1 is F, Cl, Br, NO2, C1-C6 alkyl, CF3, or OCH3;
R2 is, and
R3 is C1-C6 alkyl;

(5) reacting the compound of the formula 9 above with Dess-Martin periodinane (DMP), to provide a compound of the following formula 10:, wherein:
R is F, Cl, Br, NO2, C1-C6 alkyl, CF3, or OCH3;
R1 is F, Cl, Br, NO2, C1-C6 alkyl, CF3, or OCH3;
R2 is, and
R3 is C1-C6 alkyl; and

(6) reacting the compound of the formula 10 above with an acid of the following formula 5:

HX   5

wherein:
HX is a pharmaceutically acceptable inorganic acid or a pharmaceutically acceptable organic acid selected from the group consisting of hydrofluoric acid, hydrochloric acid, hydrobromic acid, nitric acid, phosphoric acid, sulfuric acid, formic acid, acetic acid, trifluoroacetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, picric acid, benzoic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and naphthalenesulfonic acid;

to provide the compound of the following formula 1 above:, wherein:
R is F, Cl, Br, NO2, C1-C6 alkyl, CF3, or OCH3;
R1 is F, Cl, Br, NO2, C1-C6 alkyl, CF3, or OCH3;
R2 is, R3 is C1-C6 alkyl; and
HX is a pharmaceutically acceptable inorganic acid or a pharmaceutically acceptable organic acid selected from the group consisting of hydrofluoric acid, hydrochloric acid, hydrobromic acid, nitric acid, phosphoric acid, sulfuric acid, formic acid, acetic acid, trifluoroacetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, picric acid, benzoic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and naphthalenesulfonic acid.