IP Library › Granted Patent US 12,319,677
Granted Patent B2
US 12,319,677 · App. 18/222,679 · Granted Jun 3, 2025

Process for the production of 5-(4-((2S,5S)-5-(4-chlorobenzyl)-2-methyl-morpholino)piperidin-1-yl)-1H-1,2,4-triazol-3-amine

Inventors: Grzegorz Witkowski (Warsaw, PL); Marta Magdycz (Chotomów, PL); Magdalena Tyszkiewicz (Warsaw, PL); Marcin Zakrzewski (Warsaw, PL); Stanisław Pikul (Jasło, PL)
Assignee: Molecure S.A.
C07D413/14C07D211/74C07D413/04
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Quick Facts
Patent No.
US 12,319,677
App. No.
18/222,679
Granted
Jun 3, 2025
Kind
B2
Abstract

The present invention relates to a process for the synthesis of 5-(4-((2S,5S)-5-(4-chlorobenzyl)-2-methylmorpholino)piperidin-1-yl)-1H-1,2,4-triazol-3-amine in two hydrated crystalline forms and in one anhydrous crystalline form. The present invention further relates to methyl (Z)-4-((2S,5S)-5-(4-chlorobenzyl)-2-methylmorpholino)-N-cyanopiperidine-1-carbimidothioate which is an intermediate in this process.

Claims (20)

1. A solid crystalline form of 5-(4-((2S,5S)-5-(4-chlorobenzyl)-2-methylmorpholino)piperidin-1-yl)-1H-1,2,4-triazol-3-amine of formula 1

hydrated form I, characterized by:

a) an XRPD pattern comprising at least the following peaks: 14.20±0.1, 15.58±0.1, 18.30±0.1, 23.22±0.1, and 23.68±0.1° 2-theta; and

b) characteristic infrared (IR) spectrum comprising IR bands at 3318, 3206, 2963, 2934, 2859, 2833, 1636, 1589, 1553, 1489, 1462, 1404, 1346,1314, 1277, 1250, 1151, 117, 1092, 1069, 1013, 917, 868, 829, 800, 764, 725, and 673 cm −1 .

2. A solid crystalline form of 5-(4-((2S,5S)-5-(4-chlorobenzyl)-2-methylmorpholino) piperidin-1-yl)-1H-1,2,4-triazol-3-amine of formula 1

anhydrous form, characterized by

an XRPD pattern comprising at least the following peaks: 14.61±0.1, 19.86±0.1, and 21.22±0.1° 2-theta.

3. A process for the preparation of a composition consisting essentially of an anhydrous form of 5-(4-((2S,5S)-5-(4-chlorobenzyl)-2-methylmorpholino) piperidin-1-yl)-1H-1,2,4-triazol-3-amine of formula 1

comprising azeotropic distillation of a solution of the starting compound of formula 1 hydrated form I or II.

4. The process of claim 3 , wherein the starting compound of formula 1 is the hydrated form I.

5. A solid crystalline form of 5-(4-((2S,5S)-5-(4-chlorobenzyl)-2-methylmorpholino) piperidin-1-yl)-1H-1,2,4-triazol-3-amine of formula 1

hydrated form II, characterized by

a) an XRPD pattern comprising at least the following peaks: 15.48±0.1, 19.76±0.1, 22.54±0.1, and 22.86±0.1° 2-theta; and

b) characteristic infrared (IR) spectrum comprising IR bands at 3325, 2963, 2814, 1634, 1580, 1553, 1489, 1460, 1418, 1389, 1343, 1279, 1248, 1206, 1151, 1119, 1090, 1069, 1047, 1013, 991, 914, 866, 831, 797, 760, 665, and 600 cm −1 .

6. The solid crystalline form of claim 2 , further characterized by an XRPD pattern comprising the following peaks: 5.81, 7.39, 9.95, 11.53, 11.97, 12.39, 13.13, 14.07, 14.60, 14.81, 15.11, 16.09, 15.45, 17.15, 17.67, 17.85, 18.21, 18.68, 19.21, 19.84, 20.75, 21.22, 22.24, 23.00, 24.22, 24.98, and 27.48±0.1° 2-theta.

7. The solid crystalline form of claim 2 , having a characteristic infrared (IR) spectrum comprising IR bands at 3252, 3198, 3119, 2955, 2924, 2857, 2793, 1666, 1599, 1543, 1483, 1456, 1404, 1337, 1283, 1248, 1136, 1117, 1094, 1072, 1053, 1013, 908, 858, 795, and 718 cm −1 .

8. The solid crystalline form of claim 2 , further characterized by a DSC thermogram, with onset at 175.83° C.±2.0° C. and a peak at 177.59° C.±2.0° C.

9. A composition consisting essentially of the solid crystalline form of claim 1 .

10. A composition consisting essentially of the solid crystalline form of claim 2 .

11. A composition consisting essentially of the solid crystalline form of claim 5 .

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 19, 2023
From: WITKOWSKI, GRZEGORZ; MAGDYCZ, MARTA; TYSZKIEWICZ, MAGDALENA; PIKUL, STANISLAW
To: ONCOARENDI THERAPEUTICS S.A.
Reel/Frame 064307/0215 →
EMPLOYMENT AGREEMENT Recorded Jul 19, 2023
From: ZAKRZEWSKI, MARCIN
To: ONCOARENDI THERAPEUTICS SP Z O. O.
Reel/Frame 064335/0147 →
CHANGE OF NAME Recorded Jul 19, 2023
From: ONCOARENDI THERAPEUTICS S.A.
To: MOLECURE S.A.
Reel/Frame 064336/0487 →
CHANGE OF NAME Recorded Jul 19, 2023
From: ONCOARENDI THERAPEUTICS SP Z O. O.
To: ONCOARENDI THERAPEUTICS S.A.
Reel/Frame 064336/0490 →
Priority Claims (1)
PL 431269 · Sep 25, 2019 · national
Continuity (3)
Division 17032232 · Sep 25, 2020
Provisional Application 62905494 · Sep 25, 2019
Related Publication 20240025889A1 · Jan 25, 2024
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