Developing an atroposelective dynamic kinetic resolution of MRTX1719 by resolving incompatible chemical operations

被引：10

作者：

Achmatowicz, Michal M. ^{[1
]}

Chen, Cheng-yi ^{[1
]}

Snead, David R. ^{[1
]}

机构：

[1] Mirati Therapeut, 3545 Cray Ct, San Diego, CA 92121 USA

来源：

CHEMICAL COMMUNICATIONS | 2022年 / 58卷 / 74期

关键词：

OPTICAL RESOLUTION; ATROPISOMERISM;

D O I：

10.1039/d2cc03627d

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A high-yielding protocol for atropisomeric resolution was developed by rectifying incompatibilities between crystallization and epimerization via continuous processing. Application toward synthesis of MRTX1719, a densely functionalized active pharmaceutical ingredient (API), improved yield from 37% to 87%. This protocol provides a complementary means to access rotamers which challenge current asymmetric methodologies, and greatly improves sustainability by decreasing the consumption of solvent and advanced synthetic intermediates.

引用

页码：10365 / 10367

页数：3

共 19 条

[1] Crystallization-induced diastereomer transformations [J].

Brands, Karel M. J. ;

Davies, Antony J. .

CHEMICAL REVIEWS, 2006, 106 (07) :2711-2733

[2] Atroposelective synthesis of axially chiral biaryl compounds [J].

Bringmann, G ;

Mortimer, AJP ;

Keller, PA ;

Gresser, MJ ;

Garner, J ;

Breuning, M .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2005, 44 (34) :5384-5427

[3] The Challenge of Atropisomerism in Drug Discovery [J].

Clayden, Jonathan ;

Moran, Wesley J. ;

Edwards, Paul J. ;

LaPlante, Steven R. .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2009, 48 (35) :6398-6401

[4] Review and Modeling of Crystal Growth of Atropisomers from Solutions [J].

Derdour, Lotfi ;

Chan, Eric J. ;

Skliar, Dimitri .

PROCESSES, 2019, 7 (09)

[5] Recent encounters with atropisomerism in drug discovery [J].

Glunz, Peter W. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2018, 28 (02) :53-60

[6] EPIMERIZATION-CRYSTALLIZATION METHOD IN OPTICAL RESOLUTION OF 2,2'-DIHYDROXY-1,1'-BINAPHTHYL, AND KINETIC-STUDY [J].

KAWASHIMA, M ;

HIRATA, R .

BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, 1993, 66 (07) :2002-2005

[7] DIRECT OPTICAL RESOLUTION OF 2,2'-DIHYDROXY-1,1'-BINAPHTHYL [J].

KAWASHIMA, M ;

HIRAYAMA, A .

CHEMISTRY LETTERS, 1990, (12) :2299-2300

[8] Continuous Flow Chiral Amine Racemization Applied to Continuously Recirculating Dynamic Diastereomeric Crystallizations [J].

Kwan, Maria H. T. ;

Breen, Jessica ;

Bowden, Martin ;

Conway, Louis ;

Crossley, Ben ;

Jones, Martin F. ;

Munday, Rachel ;

Pokar, Nisha P. B. ;

Screen, Thomas ;

Blacker, A. John .

JOURNAL OF ORGANIC CHEMISTRY, 2021, 86 (03) :2458-2473

[9] Assessing Atropisomer Axial Chirality in Drug Discovery and Development [J].

LaPlante, Steven R. ;

Fader, Lee D. ;

Fandrick, Keith R. ;

Fandrick, Daniel R. ;

Hucke, Oliver ;

Kemper, Ray ;

Miller, Stephen P. F. ;

Edwards, Paul J. .

JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (20) :7005-7022

[10]

Lv Y., 2022, NAT COMMUN, V13, P27813

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