ZA200208014B - Macrocyclic NS3-serine protease inhibitors of hepatitis C virus comprising alkyl and aryl alanine P2 moieties. - Google Patents

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Publication number

ZA200208014B

ZA200208014B ZA200208014A ZA200208014A ZA200208014B ZA 200208014 B ZA200208014 B ZA 200208014B ZA 200208014 A ZA200208014 A ZA 200208014A ZA 200208014 A ZA200208014 A ZA 200208014A ZA 200208014 B ZA200208014 B ZA 200208014B

Authority

ZA

South Africa

Prior art keywords

mmol

equiv

reaction mixture

solution

concentrated

Prior art date

2000-04-19

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• -1 aryl alanine Chemical compound 0.000 title claims description 69
• 241000711549 Hepacivirus C Species 0.000 title claims description 38
• 239000003001 serine protease inhibitor Substances 0.000 title claims description 4
• 125000000217 alkyl group Chemical group 0.000 title description 26
• 235000004279 alanine Nutrition 0.000 title description 2
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 244
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• 239000011541 reaction mixture Substances 0.000 claims description 167
• 150000001875 compounds Chemical class 0.000 claims description 152
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 133
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 119
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 84
• 239000007787 solid Substances 0.000 claims description 79
• 238000000034 method Methods 0.000 claims description 72
• 235000019439 ethyl acetate Nutrition 0.000 claims description 65
• 229910001868 water Inorganic materials 0.000 claims description 64
• 238000002360 preparation method Methods 0.000 claims description 61
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 60
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 60
• 239000000203 mixture Substances 0.000 claims description 59
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 59
• 239000012044 organic layer Substances 0.000 claims description 56
• 238000000746 purification Methods 0.000 claims description 48
• 239000012267 brine Substances 0.000 claims description 42
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 claims description 42
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 40
• 239000011347 resin Substances 0.000 claims description 40
• 229920005989 resin Polymers 0.000 claims description 40
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 39
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 39
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 39
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