609799-22-6 Usage
Description
Tasimelteon, which is marketed by Vanda Pharmaceuticals as
Hetlioz and developed in partnership with Bristol-Myers Squibb,
is a drug that was approved by the US FDA in January 2014 for
the treatment of non-24-hour sleep–wake disorder (also called
Non-24, N24 and N24HSWD). Tasimelteon is a melatonin MT1
and MT2 receptor agonist; because it exhibits a greater affinity to
the MT2 receptor than MT1, is also known as Dual Melatonin
Receptor Agonist.234 Two randomized controlled trials (phases II
and III) demonstrated that tasimelteon improved sleep latency
and maintenance of sleep with a shift in circadian rhythms, and
therefore has the potential to treat patients with transient insomnia
associated with circadian rhythm sleep disorders. Preclinical
studies showed that the drug has similar phase-shifting properties
to melatonin, but with less vasoconstrictive effects.
Uses
Tasimelteon is a novel drug, used in the treatment of non-24 hour sleep-wake disorder. It helps to correct the circadian rhythm disorder often seen in patients who are visually impaired.
Definition
ChEBI: A member of the class of 1-benzofurans that is propionamide in which one of the amide hydrogens is replaced by a [(1R,2R)-2-(2,3-dihydro-1-benzofuran-4-yl)cyclopropyl]methyl group. A melatonin receptor agonist used for the
treatment of non-24-hour sleep-wake disorder.
Synthesis
Activation of commercial bis-ethanol 250 with 2.5 equivalents
of the Vilsmeier salt 251 followed by treatment with base resulted
an intramolecular cyclization reaction with the proximal phenol
and concomitant elimination of the remaining imidate to deliver
the vinylated dihydrobenzofuran 252 in 76% yield. Interestingly,
this reaction could be performed on multi-kilogram scale, required
no chromatographic purification, and generated environmentallyfriendly
DMF and HCl as byproducts. Sharpless asymmetric
dihydroxylation of olefin 252 delivered diol 253 in 86% yield and
impressive enantioselectivity (>99% ee). This diol was then activated
with trimethylsilyl chloride and then treated with base to generate epoxide 254. Next, a modified Horner–Wadsworth–
Emmons reaction involving triethylphosphonoacetate (TEPA, 255)
was employed to convert epoxide 254 to cyclopropane 256.
The reaction presumably proceeds through removal of the acidic
TEPA proton followed by nucleophilic attack at the terminal epoxide
carbon. The resulting alkoxide undergoes an intramolecular
phosphoryl transfer reaction resulting in an enolate, which then
attacked the newly formed phosphonate ester in an SN2 fashion
resulting in the trans-cyclopropane ester, which was ultimately
saponified and re-acidified to furnish cyclopropane acid 256.
Conversion of this acid to the corresponding primary amide preceded
carbonyl reduction with sodium borohydride. The resulting
amine was acylated with propionyl chloride to furnish tasimelteon
(XXXI) as the final product in 86% yield across the four-step
sequence.
Check Digit Verification of cas no
The CAS Registry Mumber 609799-22-6 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 6,0,9,7,9 and 9 respectively; the second part has 2 digits, 2 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 609799-22:
(8*6)+(7*0)+(6*9)+(5*7)+(4*9)+(3*9)+(2*2)+(1*2)=206
206 % 10 = 6
So 609799-22-6 is a valid CAS Registry Number.
InChI:InChI=1/C15H19NO2/c1-2-15(17)16-9-10-8-13(10)11-4-3-5-14-12(11)6-7-18-14/h3-5,10,13H,2,6-9H2,1H3,(H,16,17)/t10-,13+/m0/s1
609799-22-6Relevant articles and documents
Development of Jacobsen Asymmetric Epoxidation and Sharpless Asymmetric Dihydroxylation Methods for the Large-Scale Preparation of a Chiral Dihydrobenzofuran Epoxide
Siva Prasad,Vu, Truc,Totleben, Michael J.,Crispino, Gerard A.,Kacsur, David J.,Swaminathan, Shankar,Thornton, John E.,Fritz, Alan,Singh, Ambarish K.
, p. 821 - 827 (2003)
Two well-known methodologies, the Jacobsen asymmetric epoxidation (AE) and the Sharpless asymmetric dihydroxylation (AD) followed by epoxidation, were evaluated for the large-scale preparation of a chiral dihydrobenzofuran epoxide. The AE method was improved by substituting ethanol for dichloromethane for the dissolution of meta-chloroperbenzoic acid (m-CPBA). This change in solvent had a significant impact on scaleability of the AE procedure by preventing crystallization of the m-CPBA during addition to the cold reaction mixture. Factors affecting the enantiomeric excess and yield of the chiral epoxide resulting from AD followed by epoxidation were studied. The Sharpless AD reaction provided the intermediate chiral diol as a solid with high ee (>98.5%). The Sharpless-Kolb conversion of the chiral diol to a chiral epoxide was modified to potassium tert-butoxide/tetrahydrofuran to obtain the product in good yield (74-84%) and high ee (>98%). Both the AE and AD processes were scaled up to prepare large quantities of the chiral epoxide.
An efficient and practical asymmetric synthesis of (?)-tasimelteon
Wang, Wenbing,Meng, Xiangwei,Zhu, Jianrong,Zhang, Xingxian
, p. 129 - 135 (2019/01/24)
Tasimelteon is a useful drug for the treatment of Non-24 in totally blind individuals. An efficient and convenient asymmetric synthesis of tasimelteon has been developed from 4-vinyl-2,3-dihydrobenzofuran through six steps in 53% overall yield using the Corey–Bakshi–Shibata (CBS0 asymmetric reduction of ketone as a key step.
PROCESS FOR THE PREPARATION OF ENANTIOMERICALLY ENRICHED DIHYDROBENZOFURANS AND INTERMEDIATE COMPOUNDS OBTAINED IN THE PROCESS
-
, (2018/09/12)
It is described an industrially viable and advantageous process for the preparation of (N- (((1R,2R)-2-(2,3-dihydrobenzofuran-4-yl)cyclopropyl)methyl)propionamide, compound having the formula depicted below and generally known as Tasimelteon, or of intermediates useful in the synthesis thereof: The invention also relates to salts obtained as intermediates of the process.
