Aprepitant

CAT#: H100065

CAS#: 170729-80-3

Description: Aprepitant is a small molecule, high-affinity substance P antagonist (SPA) with antiemetic activity. Crossing the blood brain barrier, aprepitant binds selectively to the human substance P/neurokinin 1 receptor in the central nervous system (CNS), thereby inhibiting receptor binding of endogenous substance P and substance P-induced emesis. This agent has little or no affinity for serotonin type 3 (5-HT3), dopamine, and corticosteroid receptors.

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Synthetic Routes

Aprepitant - Synthetic Route 1

Aprepitant route01

Synthetic reference

Brands, Karel M. J.; Payack, Joseph F.; Rosen, Jonathan D.; Nelson, Todd D.; Candelario, Alexander; Huffman, Mark A.; Zhao, Matthew M.; Li, Jing; Craig, Bridgette; Song, Zhiguo J.; Tschaen, David M.; Hansen, Karl; Devine, Paul N.; Pye, Philip J.; Rossen, Kai; Dormer, Peter G.; Reamer, Robert A.; Welch, Christopher J.; Mathre, David J.; Tsou, Nancy N.; McNamara, James M.; Reider, Paul J.Efficient Synthesis of NK1 Receptor Antagonist Aprepitant Using a Crystallization-Induced Diastereoselective Transformation. Journal of the American Chemical Society. Volume 125. Issue 8. Pages 2129-2135. 2003.

Aprepitant - Synthetic Route 2

Aprepitant route02

Synthetic reference

Hale, Jeffrey J.; Mills, Sander G.; MacCoss, Malcolm; Finke, Paul E.; Cascieri, Margaret A.; Sadowski, Sharon; Ber, Elzbieta; Chicchi, Gary G.; Kurtz, Marc; Metzger, Joseph; Eiermann, George; Tsou, Nancy N.; Tattersall, F. David; Rupniak, Nadia M. J.; Williams, Angela R.; Rycroft, Wayne; Hargreaves, Richard; MacIntyre, D. Euan. Structural Optimization Affording 2-(R)-(1-(R)-3,5-Bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluoro)phenyl-4- (3-oxo-1,2,4-triazol-5-yl)methylmorpholine, a Potent, Orally Active, Long-Acting Morpholine Acetal Human NK-1 Receptor Antagonist. Journal of Medicinal Chemistry. Volume 41. Issue 23. Pages 4607-4614. 1998.

Aprepitant - Synthetic Route 3

Aprepitant route03

Synthetic reference

Zhao, Matthew M.; McNamara, James M.; Ho, Guo-Jie; Emerson, Khateeta M.; Song, Zhiguo J.; Tschaen, David M.; Brands, Karel M. J.; Dolling, Ulf-H.; Grabowski, Edward J. J.; Reider, Paul J.; Cottrell, Ian F.; Ashwood, Michael S.; Bishop, Brian C.Practical Asymmetric Synthesis of Aprepitant, a Potent Human NK-1 Receptor Antagonist, via a Stereoselective Lewis Acid-Catalyzed Trans Acetalization Reaction. Journal of Organic Chemistry. Volume 67. Issue 19. Pages 6743-6747. 2002.

Aprepitant - Synthetic Route 4

Aprepitant route04

Synthetic reference

Mazuela, Javier; Antonsson, Thomas; Johansson, Magnus J.; Knerr, Laurent; Marsden, Stephen P. Direct synthesis of N-alkyl arylglycines by organocatalytic asymmetric transfer hydrogenation of N-alkyl aryl imino esters. Organic Letters. Volume 19. Issue 20. Pages 5541-5544. 2017.

Aprepitant - Synthetic Route 5

Aprepitant route05

Synthetic reference

Petasis, Nicos A.; Morshed, M. Monzur; Ahmad, M. Syarhabil; Hossain, M. Mahmun; Trippier, Paul C. Bis(cyclopentadienyl)dimethyltitanium. e-EROS Encyclopedia of Reagents for Organic Synthesis. University of Southern California. Pages 1-13. 2012.

Aprepitant - Synthetic Route 6

Aprepitant route06

Synthetic reference

Elati, Chandrashekar R.; Kolla, Naveenkumar; Gangula, Srinivas; Naredla, Anitha; Vankawala, Pravinchandra J.; Avinigiri, Muttu L.; Chalamala, Subrahmanyeswararao; Sundaram, Venkatraman; Mathad, Vijayavitthal T.; Bhattacharya, Apurba; Bandichhor, Rakeshwar.A convergent approach to the synthesis of aprepitant: A potent human NK-1 receptor antagonist.Tetrahedron Letters. Volume 48. Issue 45. Pages 8001-8004. 2007.

Aprepitant - Synthetic Route 7

Aprepitant route07

Synthetic reference

Gangula, Srinivas; Elati, Chandrashekhar R.; Mudunuru, Satish Varma; Nardela, Anitha; Dongamanti, Ashok; Bhattacharya, Apurba; Bandichhor, Rakeshwar. Synthesis of All Enantiomerically Pure Diastereomers of Aprepitant. Synthetic Communications. Volume 40. Issue 15. Pages 2254-2268.2010.

Aprepitant - Synthetic Route 8

Aprepitant route08

Synthetic reference

Liu, Yan; Tang, Tuo-Xian; Pei, Xiao-Qiong; Zhang, Chao; Wu, Zhong-Liu. Identification of ketone reductase ChKRED20 from the genome of Chryseobacterium sp. CA49 for highly efficient anti-Prelog reduction of 3,5-bis(trifluoromethyl)acetophenone. Journal of Molecular Catalysis B: Enzymatic. Volume 102. Pages 1-8. 2014.

Aprepitant - Synthetic Route 9

Aprepitant route09

Synthetic reference

Su, Wenrou; Ni, Feng; Zhang, Jin; Zhu, Ben; Li, Jianqi. Synthesis of aprepitant. Zhongguo Yiyao Gongye Zazhi. Volume 45. Issue 10. Pages 901-905.2014.

Aprepitant - Synthetic Route 10

Aprepitant route010

Synthetic reference

Crocker, Louis; McCauley, James.Polymorphic form of the tachykinin receptor antagonist 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluorophenyl)-4-(3-(5-oxo-1H,4H-1,2,4-triazolo))methylmorpholine. Assignee Merck & Co., Inc. 1999.