Process for preparing a composition comprising enantiomerically enriched pyrrolo[2,3-d]pyrimidines

1 . A process for preparing a pharmaceutical composition comprising:

(a) a compound of Formula I:

or a pharmaceutically acceptable salt thereof,

wherein:

Y 1 is hydrogen (H) or deuterium (D);

(i) Y 2 is independently H; or

Y 2 is independently D; and

(ii) Y 3 is independently H; or

Y 3 is independently D; and

(b) an amount in the range of from 0.01% to 2% by weight of (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(cyclopentyl-2,2,3,3,4,4,5,5-d 8 ) propanamide (Compound A) of the following formula:

or a pharmaceutically acceptable salt thereof;

wherein the process comprises the following step:

reacting a compound of Formula II′:

or a pharmaceutically acceptable salt thereof,

wherein:

Y 1 is hydrogen (H) or deuterium (D);

(i) Y 2 is independently H; or

Y 2 is independently D;

(ii) Y 3 is independently H; or

Y 3 is independently D;

R 6 is independently H, C(O)CF 3 , C(O)OC(CH 3 ) 3 , C(phenyl) 3 , or S(O) 2 CF 3 ; and

R 1 ′ is independently C 1 -C 10 alkyl or C 2 -C 10 alkenyl; or

R 1 ′ and R 1 ′, taken together with the oxygen atoms to which they are attached, form a 5- to 7-membered heterocyclyl, wherein the 5- to 7-membered heterocyclyl is optionally substituted with one or more CH 3 substituents;

with an acid, to form the pharmaceutical composition comprising (a) the compound of Formula I above, or a pharmaceutically acceptable salt thereof, and (b) an amount in the range of from 0.01% to 2% by weight of (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(cyclopentyl-2,2,3,3,4,4,5,5-d 8 ) propanamide (Compound A) above.

2 . The process according to claim 1 , wherein the pharmaceutical composition comprises an amount in the range of from 0.05% to 1% by weight of Compound A.

3 . The process according to claim 1 , wherein the pharmaceutical composition comprises an amount in the range of from 0.01% to 0.7% by weight of Compound A.

4 . The process according to claim 1 , wherein the pharmaceutical composition comprises an amount in the range of from 0.1% to 0.6% by weight of Compound A.

5 . The process according to claim 1 , wherein the pharmaceutical composition comprises an amount in the range of from 0.1% to 0.5% by weight of Compound A.

6 . The process according to claim 1 , wherein the pharmaceutical composition comprises an amount in the range of from 0.2% to 0.4% by weight of Compound A.

7 . The process according to claim 1 , wherein the pharmaceutical composition comprises an amount in the range of from 0.3% to 0.5% by weight of Compound A.

8 . The process according to claim 1 , wherein the deuterium incorporation at each deuterium position is at least 90%.

9 . The process according to claim 1 , wherein the deuterium incorporation at each deuterium position is at least 95%.

10 . The process according to claim 1 , wherein the deuterium incorporation at each deuterium position is at least 97%.

11 . The process according to claim 1 , wherein:

Y 1 is hydrogen (H);

Y 2 is independently D; and

Y 3 is independently D.

12 . The process according to claim 1 , wherein:

Y 1 is hydrogen (H);

Y 2 is independently H; and

Y 3 is independently H.

13 . The process according to claim 1 , wherein at least one R 6 is C(O)CF 3 , C(O)OC(CH 3 ) 3 , C(phenyl) 3 , or S(O) 2 CF 3 .

14 . The process according to claim 1 , wherein R 6 is independently H.

15 . The process according to claim 1 , wherein R 1 ′ is independently CH 3 .

16 . The process according to claim 1 , wherein the acid is selected from the group consisting of hydrochloric acid, phosphoric acid, and trifluoracetic acid (TFA), or a combination thereof.