| Company Name: |
Suzhou yacoo science co.,Ltd
|
| Tel: |
0512-87182056 18013166090 |
| Email: |
lingling.qi@yacoo.com.cn |
| Products Intro: |
Product Name:Ximelagatran
Purity:98% Package:10g;50g;1kg;5Kg;25kg;
|
| Company Name: |
Suzhou yacoo science co.,Ltd
|
| Tel: |
0512-87182056 13451648594 |
| Email: |
sales@yacoo.com.cn |
| Products Intro: |
Product Name:Ximelagatran
Purity:98% Package:10g;50g;1kg;5Kg;25kg;
|
|
| | Ximelagatran Basic information |
| Product Name: | Ximelagatran | | Synonyms: | Ximelagatran | | CAS: | | | MF: | | | MW: | 0 | | EINECS: | | | Product Categories: | | | Mol File: | Mol File | ![Ximelagatran Structure]() |
| | Ximelagatran Chemical Properties |
| Melting point | 70-75oC | | storage temp. | Hygroscopic, -20°C Freezer, Under inert atmosphere | | solubility | Chloroform (Slightly), Methanol (Slightly) | | form | Solid | | color | White | | Stability: | Hygroscopic |
| | Ximelagatran Usage And Synthesis |
| Description | Ximelagatran (XII), a prodrug of a direct thrombin
inhibitor, melagatrin, was approved in the European Union
in December, 2003, for the prevention of venous
thromboembolic events in patients undergoing major
elective orthopedic surgery, that is, hip or knee replacement. The FDA, however, did not approve the drug in the
US based on the recommendation of the advisory panel. | | Uses | Antithrombotic agent. | | Brand name | Exanta (proposed) (AstraZeneca). | | Synthesis | Synthesis of melagatran and ximelagatran has been published
in several patents and is shown in the Scheme. The
synthesis is based on coupling of key fragment 86 with acid
91 followed by elaboration to provide ximelagatran. The
synthesis of the key intermediate, shown in Scheme 12, was
reported to be scalable in high yields. Reaction of
benzyl bromide 81 with ditertbutylimino dicarboxylate in
the presence of sodium hydride gave 82, which was reacted
with hydroxyl amine in aqueous ethanol to give hydroxyl
amidine 83 in 80% yield. Immediate hydrogenation removed
the hydroxyl group and gave 84, which was protected with
benzyl chloroformate to provide 85. Deprotection of 85 with
acid furnished amidine intermediate 86. Synthesis of
fragment 91 was done by hydrogenation of N-BOC phenyl
glycine (87) in the presence of rhodium in alumina to
provide cyclohexyl amino acid 88 in 83% yield. Coupling of
the acid 88 with azetidine 2-methyl ester (89) using EDC
provided 90 in 92% yield. Hydrolysis of the ester followed
by coupling to a key intermediate benzyl carbamate protected aminino benzyl amine 86 under EDC coupling conditions
provided 92 in 86%. Subsequent hydrogenolysis removed
the benzyl carbamate and provided intermediate 93. To
complete the synthesis, the intermediate 93 was reacted with
activated double ester 94 to furnish simultaneously protected
and activated amidine 95. Removal of the BOC group
(TFA) followed by reaction with ethyl (Otrifluoromethanesulfonyl)-
glycolate in the presence of base
provided esterified intermediate 97. Reaction of 97 with
hydroxyl amine hydrochloride in the presence of base
deprotected and installed hydroxyl amidine product,
ximelagatrin (XII). 
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| | Ximelagatran Preparation Products And Raw materials |
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