US 12,304,896 B2
Highly purified pharmaceutical grade tasimelteon
Deepak Phadke, Olathe, KS (US); Natalie M. Platt, Columbia, MD (US); and Ravi K. Pandrapragada, Clarksburg, MD (US)
Assigned to VANDA PHARMACEUTICALS INC., Washington, DC (US)
Filed by VANDA PHARMACEUTICALS INC., Washington, DC (US)
Filed on Jun. 13, 2024, as Appl. No. 18/741,969.
Application 18/741,969 is a continuation of application No. 18/362,073, filed on Jul. 31, 2023, granted, now 12,049,457.
Application 18/362,073 is a continuation of application No. 18/149,590, filed on Jan. 3, 2023, granted, now 11,760,740, issued on Sep. 19, 2023.
Application 18/149,590 is a continuation of application No. 17/455,308, filed on Nov. 17, 2021, granted, now 11,566,011, issued on Jan. 31, 2023.
Application 17/455,308 is a continuation of application No. 17/039,795, filed on Sep. 30, 2020, granted, now 11,203,581, issued on Dec. 21, 2021.
Application 17/039,795 is a continuation of application No. 16/800,721, filed on Feb. 25, 2020, granted, now 10,829,465, issued on Nov. 10, 2020.
Application 16/800,721 is a continuation of application No. 16/123,303, filed on Sep. 6, 2018, granted, now 10,611,744, issued on Apr. 7, 2020.
Application 16/123,303 is a continuation of application No. 15/117,734, granted, now 10,071,977, issued on Sep. 11, 2018, previously published as PCT/US2015/015564, filed on Feb. 12, 2015.
Claims priority of provisional application 62/087,394, filed on Dec. 4, 2014.
Prior Publication US 2024/0336584 A1, Oct. 10, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 307/81 (2006.01); C07D 307/79 (2006.01)
CPC C07D 307/81 (2013.01) [C07D 307/79 (2013.01)] 17 Claims
 
1. A process for synthesizing highly purified, pharmaceutical grade tasimelteon, the process comprising:
(a) propionylating ((1R,2R)-2-(2,3-dihydrobenzofuran-4-yl)cyclopropyl)methanamine or a salt thereof to yield tasimelteon;
(b) crystallizing the tasimelteon produced in step (a);
(c) assaying the crystallized tasimelteon from step (b) for the presence of one or both of Impurity 5 (N-((2-(2,3-dihydrobenzofuran-4-yl)-1-((2-(2,3-dihydrobenzofuran-4-yl)cyclopropyl)(propionamido)methyl) cyclopropyl)methyl)propionamide) and Impurity 6 (2-hydroxy-6-(2-(propionamidomethyl)cyclopropyl)phenethyl 2-(2-hydroxyethyl)-3-(2-(propionamidomethyl)cyclopropyl)phenyl carbonate); and
(d)(i) if the crystallized tasimelteon meets pre-set specifications for Impurity 5 or Impurity 6, or both, then collecting the highly purified, pharmaceutical grade tasimelteon or
(d)(ii) if the crystallized tasimelteon fails to meet pre-set specifications for Impurity 5 or Impurity 6, or both, then further purifying the tasimelteon and repeating steps (c) and (d), or discarding the batch.