Lusutrombopag
- CAS No.
- 1110768-00-7
- Chemical Name:
- Lusutrombopag
- Synonyms
- Lusutrombopag;Lusutrombopag Impurity 6;Lusutrombopag Impurity 39;(S,E)-3-(2,6-dichloro-4-((4-(3-(1-(hexyloxy)ethyl)-2-methoxyphenyl)thiazol-2-yl)carbamoyl)phenyl)-2-methylacrylic acid;Ethyl (S,E)-3-(2,6-dichloro-4-((4-(3-(1-(hexyloxy)ethyl)-2-methoxyphenyl)thiazol-2-yl)carbamoyl)phenyl)-2-methylacrylate;ethyl (S)-(E)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(1-hexyloxyethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylate;(S,E)-Ethyl 3-(2,6-dichloro-4-((4-(3-(1-(hexyloxy)ethyl)-2-methoxyphenyl)thiazol-2-yl)carbamoyl)phenyl)-2-methylacrylate;(S)-ethyl 3-(2,6-dichloro-4-((4-(3-(1-(hexyloxy)ethyl)-2-methoxyphenyl)thiazol-2-yl)carbamoyl)phenyl)-2-methylacrylate(WXG02540);2-Propenoic acid, 3-[2,6-dichloro-4-[[[4-[3-[(1S)-1-(hexyloxy)ethyl]-2-methoxyphenyl]-2-thiazolyl]amino]carbonyl]phenyl]-2-methyl-, ethyl ester, (2E)-
- CBNumber:
- CB62756507
- Molecular Formula:
- C31H36Cl2N2O5S
- Molecular Weight:
- 619.6
- MOL File:
- 1110768-00-7.mol
- Modify Date:
- 2023/7/14 17:33:20
Lusutrombopag Chemical Properties,Uses,Production
Description
Lusutrombopag is an orally bioavailable thrombopoietin (TPO) receptor agonist developed by Shionogi for improvement of thrombocytopenia associated with chronic liver disease in patients undergoing an elective invasive procedure (e.g., liver biopsy, liver transplantation). Thrombocytopenia, which is common among patients with chronic liver disease, increases the risk of bleeding when undergoing invasive procedures, which in turn complicates therapy and increases the risk of mortality. Lusutrombopag, which was approved in Japan in September 2015, promotes platelet production by stimulating the proliferation and differentiation of human bone marrow progenitor cells into megakaryocytes via the thrombopoietic pathway. The consequent increase in platelet levels avoids postponement of invasive procedures or transfusion of platelets and administration of platelet products, the current standard of care for thrombocytopenia in these patients.
Synthesis
To date, only two synthetic routes to lusutrombopag have
been reported: one in the Japanese patent literature which has
been exemplified on kilogram scale and the other a closely
related discovery route which has been reported in the United
States patent literature. Commercial 2,6-dibromoanisole
(106) was treated with isopropylmagnesium chloride to form
the corresponding Grignard reagent prior to reaction with
Weinreb amide 107, furnishing a ketone which underwent
immediate reduction with formic acid in the presence of chiral
catalyst RuCl(p-cymene)[(S,S)-Ts-DPEN] (108) and generate
the desired (S)-stereogenic alcohol 109. 
Unfortunately, neither
the yield nor the stereoselectivity of this reduction was reported
in any of the disclosures. Benzyl alcohol 109 was subjected to
Williamson etherification conditions with n-hexyl bromide to
furnish ether 110. The aryl bromide within 110 was then
converted to the corresponding Grignard reagent, which was
reacted with N-methyloxy-N-methyl-2-chloroacetamide (111),
followed by subsequent treatment with thiourea in toluene/
ethanol at elevated temperatures to give aminothiazole
intermediate 112 in 45% yield across the two-step sequence.
Next, activation of acid 113 prior to exposure to 112 facilitated
amide bond formation. Saponification of the pendant ester with
sodium hydroxide furnished luxutrombopag (XIV) in 89%
yield. Although acid 113 is not commercial, it could be
prepared from 3,5-dichlorobenzoic acid (33) via formylation
with 4-formylmorpholine, followed by a Horner-Wadsworth-Emmons reaction with triethylphosphonopropionate.
Lusutrombopag Preparation Products And Raw materials
Raw materials
Preparation Products
Lusutrombopag Suppliers
| Supplier | Tel | Country | ProdList | Advantage | Inquiry |
|---|---|---|---|---|---|
| SynZeal Research Pvt Ltd | +1 226-802-2078 | Gujarat, India | 6514 | 58 | Inquiry |
| Pharmaffiliates Analytics and Synthetics P. Ltd | +91-172-5066494 | Haryana, India | 6739 | 58 | Inquiry |
| career henan chemical co | +86-0371-86658258 +8613203830695 | China | 29811 | 58 | Inquiry |
| AFINE CHEMICALS LIMITED | +86-0571-85134551 | China | 15354 | 58 | Inquiry |
| Zhejiang J&C Biological Technology Co.,Limited | +1-2135480471 +1-2135480471 | China | 10473 | 58 | Inquiry |
| Henan Fengda Chemical Co., Ltd | +86-371-86557731 +86-13613820652 | China | 20287 | 58 | Inquiry |
| Qingdao Minzhi Yijie new material Co., LTD | +86-13589435123 +86-13589435123 | China | 240 | 58 | Inquiry |
| Qingdao Yonghefeng Economic and Trade Co., Ltd. | +86-13375559818 +86-13375559818 | China | 195 | 58 | Inquiry |
| SHANGHAI KEAN TECHNOLOGY CO., LTD. | +8613817748580 | China | 40066 | 58 | Inquiry |
| Molcoo Chemicals Inc. | 18627756402 | China | 9534 | 58 | Inquiry |