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Synthesis 2016; 48(18): 3120-3126
DOI: 10.1055/s-0035-1561865
DOI: 10.1055/s-0035-1561865
paper
A New and Practical Synthesis of Cariprazine through the Facile Construction of 2-[trans-4-(3,3-Dimethylureido)cyclohexyl]acetic Acid
Authors
Further Information
Publication History
Received: 20 March 2016
Accepted after revision: 25 April 2016
Publication Date:
23 June 2016 (online)
Abstract
A new, practical, and improved synthetic route to cariprazine is described. The key step is the facile preparation of 2-[4-(3,3-dimethylureido)cyclohexyl]acetic acid in the trans configuration through direct recrystallization. The entire synthetic procedure was accomplished under mild conditions while avoiding tedious purification processes. The trans configuration of cariprazine was confirmed by X-ray crystallographic analysis.
Key words
cariprazine - antipsychotic agents - synthetic methods - recrystallization - trans configuration - X-ray crystallographySupporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1561865.
- Supporting Information (PDF) (opens in new window)
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- 12 The byproduct was isolated by column chromatography (silica gel; CH2Cl2–MeOH, 50:1) and its structure was confirmed by 1H NMR and MS analysis. 1H NMR (400 MHz, CDCl3): δ = 7.20–7.15 (m, 2 H), 7.02–6.98 (m, 1 H), 4.50–4.48 (m, 1 H), 4.11 (q, J = 6.4 Hz, 2 H), 3.16 (br s, 4 H), 3.45 (br s, 1 H), 2.74–2.54 (m, 6 H), 2.04–2.02 (m, 2 H), 1.86–1.80 (m, 2 H), 1.53 (br s, 2 H), 1.31–1.24 (m, 4 H), 1.18–1.04 (m, 4 H). MS (ESI): m/z = 428.0 [M + H]+.
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