Synthesis and novel salt forms of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine
The present invention relates to the stereospecific synthesis of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine, its salt forms, and novel polymorphic forms of these salts.
1. A method of treating pain in a patient in need thereof comprising administration of an effective amount of (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine mono-citrate to the patient in need thereof.
2. The method of claim 1 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine mono-citrate is substantially free of (S)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine.
3. The method of claim 1 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine mono-citrate is in amorphous form and whose XRPD pattern substantially corresponds to that shown in FIG. 1 .
4. The method of claim 1 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine mono-citrate is in crystalline form and the crystalline form is characterized by an XRPD pattern comprising at least one of the following peaks:
2θ
11.02 ± 0.1
20.01 ± 0.1
22.06 ± 0.1
24.66 ± 0.1
32.13 ± 0.1
33.35 ± 0.1
34.61 ± 0.1
35.96 ± 0.1
38.65 ± 0.1
40.23 ± 0.1.
5. The method of claim 1 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine mono-citrate is in crystalline form and whose XRPD pattern substantially corresponds to that shown in FIG. 3 .
6. The method of claim 1 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine mono-citrate is in crystalline form and the crystalline form is characterized by an XRPD pattern comprising at least one of the following peaks:
2θ
9.43 ± 0.1
12.24 ± 0.1
16.24 ± 0.1
18.38 ± 0.1
19.18 ± 0.1
19.48 ± 0.1
21.52 ± 0.1
22.89 ± 0.1
23.08 ± 0.1
24.28 ± 0.1
30.77 ± 0.1
31.27 ± 0.1
32.36 ± 0.1
33.09 ± 0.1
34.86 ± 0.1
37.26 ± 0.1
37.63 ± 0.1
39.47 ± 0.1.
7. The method of claim 1 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine mono-citrate is in crystalline form and whose XRPD pattern substantially corresponds to that shown in FIG. 4 .
8. The method of claim 1 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine mono-citrate is in crystalline form and the crystalline form is characterized by an XRPD pattern comprising at least one of the following peaks:
2θ
5.05 ± 0.1
10.81 ± 0.1
14.06 ± 0.1
15.20 ± 0.1
17.43 ± 0.1
23.57 ± 0.1
24.21 ± 0.1
25.52 ± 0.1
26.95 ± 0.1.
9. The method of claim 1 , wherein the (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine mono-citrate is in crystalline form and whose XRPD pattern substantially corresponds to that shown in FIG. 5 .