Crystalline dipeptides useful in the synthesis of elamipretide
Disclosed are crystalline forms of L-Lys(Boc)-Phe-NH 2 and Boc-D-Arg-DMT.
1. A crystalline form of Compound (II),
wherein said crystalline form has characteristic peaks in its XRPD pattern at values of two theta as described in Table 2;
TABLE 2
Net
Gross
Rel.
Angle
d value
Intensity
Intensity
intensity
8.253
10.70488
3779
4204
15.0%
9.353
9.44784
20863
21225
82.9%
12.104
7.30592
20016
20338
79.6%
12.809
6.90584
2797
3120
11.1%
13.755
6.43269
11432
11758
45.4%
15.709
5.63659
906
1235
3.6%
16.307
5.43127
7500
7829
29.8%
16.556
5.35006
12773
13103
50.8%
16.725
5.29645
2495
2825
9.9%
17.557
5.04740
22493
22824
89.4%
18.006
4.92236
25154
25485
100.0%
18.756
4.72740
18203
18534
72.4%
18.90s
4.68953
4809
5141
19.1%
19.414
4.56848
12725
13056
50.6%
20.716
4.28417
899
1231
3.6%
21.259
4.17597
5074
5406
20.2%
22.357
3.97329
383u
4161
15.2%
23.009
3.86218
7511
7842
29.9%
23.163
3.83695
2203
2533
8.8%
23.511
3.78085
4659
4989
18.5%
24.208
3.67354
7257
7585
28.8%
24.809
3.58598
1940
2268
7.7%
25.060
3.55054
5627
5954
22.4%
25.767
3.45478
970
1297
3.9%
26.009
3.42308
1418
1744
5.6%
26.457
3.36613
255
580
1.0%
26.721
3.33347
161
485
0.6%
27.763
3.21073
1862
2185
7.4%
28.111
3.17181
1182
1503
4.7%
28.263
3.15505
366
687
1.5%
29.311
3.04456
1100
1418
4.40%
29.662
3.00931
616
933
2.40%
29.912
2.98476
1550
1866
6.20%
30.212
2.95583
1607
1922
6.40%
30.865
2.89475
1913
2226
7.60%
31.414
2.8454
1565
1876
6.20%
31.695
2.82084
468
778
1.90%
32.665
2.73926
657
963
2.60%
32.915
2.71901
296
602
1.20%
33.805
2.64939
326
632
1.30%
34.165
2.6223
670
976
2.70%
34.977
2.5633
485
795
1.90%
36.166
2.48167
798
1113
3.20%
36.514
2.45883
611
927
2.40%
36.813
2.43955
364
682
1.40%
37.466
2.39851
173
502
0.70%
37.966
2.36808
901
1257
3.60%
38.221
2.35285
394
764
1.60%
38.576
2.33202
878
1266
3.50%
39.114
2.30117
394
810
1.60%
39.516
2.27866
363
801
1.40%
29.311
3.04456
1100
1418
4.40%
29.662
3.00931
616
933
2.40%
29.912
2.98476
1550
1866
6.20%
30.212
2.95583
1607
1922
6.40%
30.865
2.89475
1913
2226
7.60%
31.414
2.8454
1565
1876
6.20%
31.695
2.82084
468
778
1.90%
32.665
2.73926
657
963
2.60%
32.915
2.71901
296
602
1.20%
33.805
2.64939
326
632
1.30%
34.165
2.6223
670
976
2.70%
34.977
2.5633
485
795
1.90%
36.166
2.48167
798
1113
3.20%
36.514
2.45883
611
927
2.40%
36.813
2.43955
364
682
1.40%
37.466
2.39851
173
502
0.70%
37.966
2.36808
901
1257
3.60%
38.221
2.35285
394
764
1.60%
38.576
2.33202
878
1266
3.50%
39.114
2.30117
394
810
1.60%
39.516
2.27866
363
801
1.40%.
2. A crystalline form of Compound (II),
wherein said crystalline form has characteristic peaks in its XRPD pattern as shown in FIG. 2 .
3. A crystalline form of Compound (II),
wherein said crystalline form has characteristic peaks in its XRPD pattern at values of two theta theta (θ 2θ) of: 9.3, 12.1, 16.6, 17.6, 18.0, 18.8, and 19.4.
4. The crystalline form of claim 3 , wherein said crystalline form has characteristic peaks in its XRPD pattern at values of two theta (°2θ) of: 9.3, 12.1, 13.7, 16.3, 16.6, 17.6, 18.0, 18.8, 19.4, 21.3, 23.0, 24.2, and 25.1.