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Machine translation
1. (WO2016200930) METHODS OF MAKING PROTEIN DEACETYLASE INHIBITORS
Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

CLAIMS

A method of makin compound (la):


(la)

comprising the steps of:

converting compound 1 la into compound 3a:


11a 3a

wherein X is selected from fluorine, chlorine, bromine and iodine;

Z is selected from the group consisting of -CN and -C02R; and R is Ci-C6 alkyl; and

converting compound 3a into compound (la).

2. The method of claim 1, wherein compound 1 la is prepared by a method comprising the step of:

converting compound la into compound 11a:


1a 11a

wherein X is selected from fluorine, chlorine, bromine and iodine;

Z is selected from the group consisting of -CN and -C02R; and R is Ci-C6 alkyl.

3. The method of claim 1, wherein the step of converting compound 3 a into compound (la) comprises the steps of:

converting compound 3a into compound 4a:

3a 4a ; and

converting compound 4a into compound (la).

4. The method of claim 3, wherein the step of converting compound 4a into compound (la) comprises the steps of:

converting compound 4a into compound 5a:


4a 5a

wherein X is selected from fluorine, chlorine, bromine and iodine; and R' is Ci-C6 alkyl; and

convertin compound 5a into compound (la):


5a (la)

wherein X is selected from fluorine, chlorine, bromine and iodine.

5. The method of any one of claims 1-4, wherein X is chlorine.

6. The method of any one of claims 1-5, wherein Z is C02Et.

7. The method of any one of claims 4-6, wherein R' is methyl.

8. A method of making compound (I):

(I)

comprising the steps of:

converting compound 1 lb into compound 3b:


11b 3b

wherein Z is selected from the group consisting of -CN and -C02R;

wherein R is Ci-C6 alkyl; and

converting compound 3b into compound (I).

9. The method of claim 8, wherein compound 1 lb is prepared by a method comprising the step of:

converting compound lb into com ound l ib:


1b 11b

10. The method of claim 8, wherein the step of converting compound 3b into compound (I) comprises:

converting compound 3b into compound 4:


3b ; and

converting compound 4 into compound (I).

11. The method of claim 10, wherein the step of converting compound 4 into compound

(I) comprises:

converting compound 4 into compound 5b:


4 5b

wherein R' is Ci-C6 alkyl; and

converting compound 5b into compound (I).

12. The method of any one of claims 8-10, wherein Z is C02Et.

13. The method of claim 11, wherein R' is methyl.

14. The method of any one of claims 9-13, wherein the step of converting compound lb into compound 1 lb comprises reacting compound 1 with 2-chloroaniline to obtain compound 11:


15. The method of any one of claims 8-14, wherein the step of converting compound 1 lb into compound 3b comprises reacting compound 11 with iodobenzene to obtain compound 3:


11

16. The method of any one of claims 10-15, wherein the step of converting compound 3b into compound 4 comprises comprises hydrolyzing the ester of compound 3:


17. The method of any one of claims 11-16, wherein the step of converting compound 4 into compound 5b comprises reacting compound 4 with methyl 7-aminoheptanoate to obtain compound 5 :


18. The method of any one of claims, wherein the step of converting compound 5b into compound (I) comprises reacting compound 5 with hydroxyl amine, or a salt thereof, to obtain compound (I), or a salt thereof.

19. A method of making compound (I) comprising the following steps:

(1) reacting ethyl 2-chloropyrimidine-5-carboxylate with 2-chloroaniline to obtain compound 11 :


11

reacting compound 11 with iodobenzene to obtain compound 3


(3) reacting compound 3 with aqueous base, followed by reacting with acid, to obtain compound 4:


reacting compound 4 with methyl 7-aminoheptanoate to obtain compound 5


(5) reacting compound 5 with hydroxylamine, or a salt thereof, to obtain compound (I), or a salt thereof:


(I)

20. A composition comprising:


G1

wherein Z is selected from the group consisting of-CN and -C02R; and wherein R is Ci-C6 alkyl; and

G11

wherein Z is selected from the group consisting of -CN and -C02R; and wherein R is Ci-C6 alkyl.

The composition of claim 20, wherein lb is compound 1


wherein 1 lb is compound 1


11

A composition compri


11b

wherein Z is selected from the group consisting of -CN and -C02R; and wherein R is Ci-C6 alkyl; and


wherein Z is selected from the group consisting of -CN and -C02R; and wherein R is Ci-C6 alkyl.

23. The composition of claim 22, wherein 1 lb is compound 11 :


wherein 3b is compound 3:


3

A compound having the structure of 1 lb:


11b

wherein Z is selected from the group consisting of -CN and -C02R; and wherein R is Ci-C6 alkyl.

25. The compound of claim 24, wherein Z is -C02R.

26. The compound of claim 25, wherein R is ethyl.

27. A composition comprising the compound of claim 24.

28. The composition of claim 27, further comprising compound 3:


3

A composition comprising compound 3:


wherein the composition is free from compounds de-Cl-3 and m-Cl-3:


de-Cl-3 m-Cl-3

A composition comprising compound 4:


wherein the composition is free from compounds de-Cl-4 and m-Cl-4:


de-Cl-4 m-Cl-4

wherein the composition is free from compounds de-Cl-5 and m-Cl-5: