Hepatitis c virus inhibitors
A compound, selected technology, applied in the direction of antiviral agents, drug combinations, peptides, etc., can solve problems such as viral load reduction
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Embodiment 1
[0133] Example 1: Compound 1
[0134]
[0135] plan 1
[0136]
[0137] step 1.
[0138]Add (2S,4R)-4-(biphenyl-4-yl)-4-hydroxypyrrolidine-1-carboxylic acid benzyl-2-methyl carboxylate (3236 mg, 7.5 mmol) and prop-2-ene at room temperature - To a clear solution of 1-thiol (834 mg, 9.00 mmol) in acetonitrile (40 mL) was added solid scandium(III) triflate (369 mg, 0.750 mmol) in one portion. The resulting pink solution was stirred at this temperature for 20 hours. Quenched with saturated aqueous ammonium chloride and extracted with EtOAc. The organic layer was washed with brine, MgSO 4 Dry, filter and evaporate in vacuo. The residue was purified by Biotage column eluting with 5%-50% EtOAc-Hexanes to give a mixture of diastereoisomers (2.88g, 79%) and recovered starting material (0.600g, 18%). The mixture was repurified on a Biotage column eluting with 2%-8% EtOAc-toluene to give the desired product (2S,4R)-4-(allylthio)-4-(biphenyl-4-yl ) pyrrolidine-1-carboxylate-m...
Embodiment 2
[0150] Example 2: Compound 2
[0151]
[0152] Compound 2
[0153] step 1.
[0154] To (2S, 4R)-4-(allylthio)-4-(biphenyl-4-yl)pyrrolidine-2-carboxylic acid methyl ester hydrochloride (97mg, 0.25mmol), (S)-2 - To an ice-cold slurry of (tert-butoxycarbonylamino)dec-9-enoic acid (86 mg, 0.300 mmol) and HATU (143 mg, 0.375 mmol) in dichloromethane (4 mL) was added N,N-diisopropyl Ethylamine (0.218 mL, 1.250 mmol). The resulting colorless slurry was stirred overnight at room temperature. Dilute with dichloromethane and wash with 5% citric acid. The organic layer was washed successively with 0.1 M NaOH aqueous solution and brine, washed with MgSO 4 Dry, filter and evaporate in vacuo. The residue was purified by Biotage column eluting with 1-25% EtOAc-hexane to give the desired product (2S,4R)-4-(allylthio)-4-(biphenyl-4-yl)-1 - Methyl ((S)-2-(tert-butoxycarbonylamino)dec-9-enoyl)pyrrolidine-2-carboxylate (111 mg, 0.161 mmol, 64.4% yield) as a white wax. LC-MS (retention ...
Embodiment 3
[0162] Example 3: Compound 3
[0163]
[0164] Compound 3
[0165] Scenario 2
[0166]
[0167] Compound 3
[0168] step 1.
[0169] H at 30psi 2 Atmosphere will contain (3S, 14R, 16S, E)-14-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)-2-oxo-13-thia-1-aza A container of bicyclo[12.2.1]heptadeca-10-ene-16-carboxylic acid (46 mg, 0.079 mmol), 5% sulfurized Pt / C (372 mg, 0.095 mmol) and methanol (4 mL) was placed on a Parr shaker overnight. Quenched with celite, filtered and washed with excess MeOH, dichloromethane and EtOAc. The combined filtrates were evaporated to dryness. The white residue (20 mg) was used in the next coupling reaction without further purification. LC-MS (retention time: 3.43 min, method C), MS m / z 581 (M+H).
[0170] Step 2.
[0171] To (3S, 14R, 16S)-14-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)-2-oxo-13-thia-1-azabicyclo[12.2. 1] Heptadecan-16-carboxylic acid (20mg, 0.034mmol), (1R, 2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropane...
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