| Identification | Back Directory | [Name]
RILPIVIRINE HCL | [CAS]
700361-47-3 | [Synonyms]
RILPIVIRINE HCL
Rilpivirine-d6 HCl
Rilpivirine HCl (TMC278
Rilpivirine Hydrochloride | [Molecular Formula]
C22H18N6.ClH | [MDL Number]
MFCD11046523 | [MOL File]
700361-47-3.mol | [Molecular Weight]
402.887 |
| Hazard Information | Back Directory | [Uses]
Rilpivirine Hydrochloride was shown to be able to treat and or prevent immunodeficiency virus-1. It also has uses for anti-viral therapy | [Definition]
ChEBI: A hydrochloride obtained by reaction of rilpivirine with one equivalent of hydrochloric acid. Used for treatment of HIV. | [Clinical Use]
Rilpivirine hydrochloride (Edurant), a non-nucleoside reverse
transcriptase inhibitor (NNRTI), received its approval both from
the U.S. FDA and E.U. EMA in 2011 for the treatment of HIV-1 infection in treatment-na?ve adult patients. It was discovered and
developed by Janssen Pharmaceuticals and its subsidiary Tibotec
Pharmaceuticals. As a second generation NNRTI, rilpivirine hydrochloride
displayed higher potency and longer half-life with a 25 mg
once a day dose, compared to existing NNRTIs, such as the 200 mg
BID of efavirenze (Sustiva). In late 2011, the fixed-dose
combination products of rilpivirine hydrochloride with two
nucleoside reverse transcriptase inhibitor (RTIs) emtricitabine and tenofovir disoproxil fumarate, co-developed by Gilead Science
and Tibotec, were also approved both by the FDA and EMA under
brand names Complera® and Eviplera®, respectively. | [Synthesis]
Similar
to efavirenze, rilpivirine hydrochloride is a diarylpyrimidine
(DAPY) compound, and the large-scale process synthesis begins
with commercially available 2-methylthio-4-pyrimidinone (193)
shown in the scheme.
Thioether 193 was condensed with neat 4-cyanoaniline (194) at
elevated temperature to afford diarylamine 195 in 77% yield. Subsequent
treatment of pyrimidone 195 with refluxing POCl3 provided
the corresponding chloride 196 in 77% yield.160,161 In the
presence of K2CO3, chloride 196 was treated with the (E)-cinnamonitrile
aniline 200 to give rilpivirine hydrochloride (XIX) in good
yield.158 Aniline 200 was prepared via a Heck reaction of commercially
available 4-iodo-2,6-dimethyl-benzeneamine (197) and
acrylonitrile (198) affording compound 199 as a 4:1 mixture of E/Z isomers. The distribution of E/Z olefins was increased to 98:2
by salt formation and recrystallization to ultimately provide pure
(E)-200 in 64% yield for two steps. |
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