JPWO2021194828A5 - - Google Patents
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- JPWO2021194828A5 JPWO2021194828A5 JP2022557823A JP2022557823A JPWO2021194828A5 JP WO2021194828 A5 JPWO2021194828 A5 JP WO2021194828A5 JP 2022557823 A JP2022557823 A JP 2022557823A JP 2022557823 A JP2022557823 A JP 2022557823A JP WO2021194828 A5 JPWO2021194828 A5 JP WO2021194828A5
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- Japan
- Prior art keywords
- mmol
- dcm
- stirred
- amino
- added
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 431
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 174
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 150
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 140
- -1 330 g Substances 0.000 description 139
- 239000000243 solution Substances 0.000 description 128
- 239000007787 solid Substances 0.000 description 126
- 239000000203 mixture Substances 0.000 description 123
- 239000011541 reaction mixture Substances 0.000 description 110
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 109
- 230000014759 maintenance of location Effects 0.000 description 94
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 87
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 78
- 239000011734 sodium Substances 0.000 description 66
- 235000019439 ethyl acetate Nutrition 0.000 description 64
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 64
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 63
- 238000005481 NMR spectroscopy Methods 0.000 description 58
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
- 239000012267 brine Substances 0.000 description 58
- 239000012074 organic phase Substances 0.000 description 43
- 239000003208 petroleum Substances 0.000 description 42
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 34
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 34
- 239000012044 organic layer Substances 0.000 description 33
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 33
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 31
- 238000010898 silica gel chromatography Methods 0.000 description 31
- 239000012043 crude product Substances 0.000 description 30
- 239000012071 phase Substances 0.000 description 30
- 239000000706 filtrate Substances 0.000 description 29
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 27
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
- 238000004128 high performance liquid chromatography Methods 0.000 description 26
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 25
- TXFOLHZMICYNRM-UHFFFAOYSA-N dichlorophosphoryloxybenzene Chemical compound ClP(Cl)(=O)OC1=CC=CC=C1 TXFOLHZMICYNRM-UHFFFAOYSA-N 0.000 description 25
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 25
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 24
- 239000012299 nitrogen atmosphere Substances 0.000 description 24
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 22
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 21
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 21
- 239000005457 ice water Substances 0.000 description 19
- 238000000746 purification Methods 0.000 description 19
- CQRPUKWAZPZXTO-UHFFFAOYSA-M magnesium;2-methylpropane;chloride Chemical compound [Mg+2].[Cl-].C[C-](C)C CQRPUKWAZPZXTO-UHFFFAOYSA-M 0.000 description 18
- 238000001914 filtration Methods 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 17
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
- 239000010410 layer Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000007924 injection Substances 0.000 description 15
- 238000002347 injection Methods 0.000 description 15
- 229910052938 sodium sulfate Inorganic materials 0.000 description 15
- 235000011152 sodium sulphate Nutrition 0.000 description 15
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 14
- XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 description 13
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 13
- 229910021529 ammonia Inorganic materials 0.000 description 13
- 238000001514 detection method Methods 0.000 description 13
- 239000003643 water by type Substances 0.000 description 13
- IKKXOSBHLYMWAE-QRPMWFLTSA-N islatravir Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@H]1C[C@H](O)[C@](CO)(C#C)O1 IKKXOSBHLYMWAE-QRPMWFLTSA-N 0.000 description 12
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 9
- 125000000755 henicosyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
- 239000012488 sample solution Substances 0.000 description 9
- 239000007832 Na2SO4 Substances 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- ZYJPUMXJBDHSIF-NSHDSACASA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ZYJPUMXJBDHSIF-NSHDSACASA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 7
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- CZBNUDVCRKSYDG-NSHDSACASA-N (2s)-3-(3,5-difluorophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC(F)=CC(F)=C1 CZBNUDVCRKSYDG-NSHDSACASA-N 0.000 description 6
- QFGMPXZFCIHYIR-UHFFFAOYSA-N 2-azaniumyl-3-(3,5-difluorophenyl)propanoate Chemical compound OC(=O)C(N)CC1=CC(F)=CC(F)=C1 QFGMPXZFCIHYIR-UHFFFAOYSA-N 0.000 description 6
- 239000007821 HATU Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 239000000377 silicon dioxide Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 5
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 5
- 125000001196 nonadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 235000010290 biphenyl Nutrition 0.000 description 4
- 239000004305 biphenyl Substances 0.000 description 4
- 125000006267 biphenyl group Chemical group 0.000 description 4
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- XGFDHKJUZCCPKQ-UHFFFAOYSA-N nonadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCO XGFDHKJUZCCPKQ-UHFFFAOYSA-N 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- NEFIERWXEGAMKT-PMERELPUSA-N C(C)(C)(C)OC(=O)N[C@H](C(=O)OCCCCCCCCCCCCCCCCCCC)CC1=CC(=CC(=C1)F)F Chemical compound C(C)(C)(C)OC(=O)N[C@H](C(=O)OCCCCCCCCCCCCCCCCCCC)CC1=CC(=CC(=C1)F)F NEFIERWXEGAMKT-PMERELPUSA-N 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-M L-alaninate Chemical compound C[C@H](N)C([O-])=O QNAYBMKLOCPYGJ-REOHCLBHSA-M 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 3
- KFWYWHZFCRTIGA-AWEZNQCLSA-N N[C@@H](C)C(=O)OC(CCCCCC)CCCCCC Chemical compound N[C@@H](C)C(=O)OC(CCCCCC)CCCCCC KFWYWHZFCRTIGA-AWEZNQCLSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 3
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 229920003228 poly(4-vinyl pyridine) Polymers 0.000 description 3
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000012258 stirred mixture Substances 0.000 description 3
- QNMCWJOEQBZQHB-UHFFFAOYSA-N 2-Hexyl-1-octanol Chemical compound CCCCCCC(CO)CCCCCC QNMCWJOEQBZQHB-UHFFFAOYSA-N 0.000 description 2
- ZPOYTBFBRNBWGV-UHFFFAOYSA-N 2-nonylundecan-1-ol Chemical compound CCCCCCCCCC(CO)CCCCCCCCC ZPOYTBFBRNBWGV-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- YPHSBKSXDXYLQB-LDQQKYCSSA-N FC=1C=C(C=C(C=1)F)C[C@@H](C(=O)OCCCCCCCCCCCCC)N[P@](=O)(OC1=CC=CC=C1)OC1=C(C(=C(C(=C1F)F)F)F)F Chemical compound FC=1C=C(C=C(C=1)F)C[C@@H](C(=O)OCCCCCCCCCCCCC)N[P@](=O)(OC1=CC=CC=C1)OC1=C(C(=C(C(=C1F)F)F)F)F YPHSBKSXDXYLQB-LDQQKYCSSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- GJELRZQLNVZTGF-QHCPKHFHSA-N N[C@H](C(=O)OCCCCCCCCCCCCCCC)CC1=CC(=CC(=C1)F)F Chemical compound N[C@H](C(=O)OCCCCCCCCCCCCCCC)CC1=CC(=CC(=C1)F)F GJELRZQLNVZTGF-QHCPKHFHSA-N 0.000 description 2
- GCELXSFEKSRJDB-VWLOTQADSA-N N[C@H](C(=O)OCCCCCCCCCCCCCCCCC)CC1=CC(=CC(=C1)F)F Chemical compound N[C@H](C(=O)OCCCCCCCCCCCCCCCCC)CC1=CC(=CC(=C1)F)F GCELXSFEKSRJDB-VWLOTQADSA-N 0.000 description 2
- GCARIZOXEZRURK-MHZLTWQESA-N N[C@H](C(=O)OCCCCCCCCCCCCCCCCCCC)CC1=CC(=CC(=C1)F)F Chemical compound N[C@H](C(=O)OCCCCCCCCCCCCCCCCCCC)CC1=CC(=CC(=C1)F)F GCARIZOXEZRURK-MHZLTWQESA-N 0.000 description 2
- DQDDKFMDGNBHEP-NDEPHWFRSA-N N[C@H](C(=O)OCCCCCCCCCCCCCCCCCCCC)CC1=CC(=CC(=C1)F)F Chemical compound N[C@H](C(=O)OCCCCCCCCCCCCCCCCCCCC)CC1=CC(=CC(=C1)F)F DQDDKFMDGNBHEP-NDEPHWFRSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 125000002511 behenyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- IBDMRHDXAQZJAP-UHFFFAOYSA-N dichlorophosphorylbenzene Chemical compound ClP(Cl)(=O)C1=CC=CC=C1 IBDMRHDXAQZJAP-UHFFFAOYSA-N 0.000 description 2
- FIPPFBHCBUDBRR-UHFFFAOYSA-N henicosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCO FIPPFBHCBUDBRR-UHFFFAOYSA-N 0.000 description 2
- YWKODMIQWGOHKW-UHFFFAOYSA-N methyl 2-octyldecanoate Chemical compound CCCCCCCCC(C(=O)OC)CCCCCCCC YWKODMIQWGOHKW-UHFFFAOYSA-N 0.000 description 2
- OACOSGXXQYIBBO-UHFFFAOYSA-N methyl 2-pentylheptanoate Chemical compound CCCCCC(C(=O)OC)CCCCC OACOSGXXQYIBBO-UHFFFAOYSA-N 0.000 description 2
- KJIOQYGWTQBHNH-UHFFFAOYSA-N methyl butylhexanol Natural products CCCCCCCCCCCO KJIOQYGWTQBHNH-UHFFFAOYSA-N 0.000 description 2
- HPBFNIVLYYKIPS-FQEVSTJZSA-N octadecyl (2s)-2-aminopropanoate Chemical compound CCCCCCCCCCCCCCCCCCOC(=O)[C@H](C)N HPBFNIVLYYKIPS-FQEVSTJZSA-N 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
- UFCKWKGPXVZTNX-RRKCRQDMSA-N (2R,3S,5R)-5-(6-amino-2-fluoropurin-9-yl)-2-ethynyloxolan-3-ol Chemical compound NC1=C2N=CN(C2=NC(=N1)F)[C@H]1C[C@@H]([C@H](O1)C#C)O UFCKWKGPXVZTNX-RRKCRQDMSA-N 0.000 description 1
- QFGMPXZFCIHYIR-QMMMGPOBSA-N (2s)-2-amino-3-(3,5-difluorophenyl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC(F)=CC(F)=C1 QFGMPXZFCIHYIR-QMMMGPOBSA-N 0.000 description 1
- ZKOGALMNTPHWDR-UHFFFAOYSA-N (3,5-difluorophenyl) propanoate Chemical compound CCC(=O)OC1=CC(F)=CC(F)=C1 ZKOGALMNTPHWDR-UHFFFAOYSA-N 0.000 description 1
- XFRVVPUIAFSTFO-UHFFFAOYSA-N 1-Tridecanol Chemical compound CCCCCCCCCCCCCO XFRVVPUIAFSTFO-UHFFFAOYSA-N 0.000 description 1
- BLXSFCHWMBESKV-UHFFFAOYSA-N 1-iodopentane Chemical compound CCCCCI BLXSFCHWMBESKV-UHFFFAOYSA-N 0.000 description 1
- SUBCOGZKZCCKOV-UHFFFAOYSA-N 12,12,13,13,14,14,15,15,15-nonafluoropentadecan-1-ol Chemical compound OCCCCCCCCCCCC(F)(F)C(F)(F)C(F)(F)C(F)(F)F SUBCOGZKZCCKOV-UHFFFAOYSA-N 0.000 description 1
- LAPPDPWPIZBBJY-UHFFFAOYSA-N 2-butylhexan-1-ol Chemical compound CCCCC(CO)CCCC LAPPDPWPIZBBJY-UHFFFAOYSA-N 0.000 description 1
- OKPDIVZFFUVTNZ-UHFFFAOYSA-N 2-heptylnonan-1-ol Chemical compound CCCCCCCC(CO)CCCCCCC OKPDIVZFFUVTNZ-UHFFFAOYSA-N 0.000 description 1
- JYZLSYFPFQTNNO-UHFFFAOYSA-N 2-octyldecan-1-ol Chemical compound CCCCCCCCC(CO)CCCCCCCC JYZLSYFPFQTNNO-UHFFFAOYSA-N 0.000 description 1
- NYVWQUGCZOIWAC-UHFFFAOYSA-N 2-pentylheptan-1-ol Chemical compound CCCCCC(CO)CCCCC NYVWQUGCZOIWAC-UHFFFAOYSA-N 0.000 description 1
- CZBNUDVCRKSYDG-UHFFFAOYSA-N 3-(3,5-difluorophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC1=CC(F)=CC(F)=C1 CZBNUDVCRKSYDG-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- 238000004679 31P NMR spectroscopy Methods 0.000 description 1
- JWRCXPISQSTBSE-MGGNMLNTSA-N COC1=CC=C(C(C2=CC=CC=C2)(C2=CC=CC=C2)NC2=C3N=CN([C@@H](C[C@@H]4OC(C5=CC=CC=C5)(C5=CC=CC=C5)C(C=C5)=CC=C5OC)O[C@@H]4C#C)C3=NC(F)=N2)C=C1 Chemical compound COC1=CC=C(C(C2=CC=CC=C2)(C2=CC=CC=C2)NC2=C3N=CN([C@@H](C[C@@H]4OC(C5=CC=CC=C5)(C5=CC=CC=C5)C(C=C5)=CC=C5OC)O[C@@H]4C#C)C3=NC(F)=N2)C=C1 JWRCXPISQSTBSE-MGGNMLNTSA-N 0.000 description 1
- 239000005697 Dodecan-1-ol Substances 0.000 description 1
- IOSGQMYMXYUGPY-NDEPHWFRSA-N N[C@@H](CC1=CC=CC=C1)C(=O)OCC(CCCCCCCCC)CCCCCCCCC Chemical compound N[C@@H](CC1=CC=CC=C1)C(=O)OCC(CCCCCCCCC)CCCCCCCCC IOSGQMYMXYUGPY-NDEPHWFRSA-N 0.000 description 1
- XSVVHABRZSHBDT-MHZLTWQESA-N N[C@@H](CC1=CC=CC=C1)C(=O)OCCCCCCCCCCCCCCCCCCC Chemical compound N[C@@H](CC1=CC=CC=C1)C(=O)OCCCCCCCCCCCCCCCCCCC XSVVHABRZSHBDT-MHZLTWQESA-N 0.000 description 1
- DZRUHYKHTHAYKE-NDEPHWFRSA-N N[C@@H](CC1=CC=CC=C1)C(=O)OCCCCCCCCCCCCCCCCCCCC Chemical compound N[C@@H](CC1=CC=CC=C1)C(=O)OCCCCCCCCCCCCCCCCCCCC DZRUHYKHTHAYKE-NDEPHWFRSA-N 0.000 description 1
- XVDKHMOGGNJSLR-SANMLTNESA-N N[C@H](C(=O)OCCCCCCCCCCCCCCCCCC)CC1=CC(=CC(=C1)F)F Chemical compound N[C@H](C(=O)OCCCCCCCCCCCCCCCCCC)CC1=CC(=CC(=C1)F)F XVDKHMOGGNJSLR-SANMLTNESA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-M alaninate Chemical compound CC(N)C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-M 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- RNJZAOHMJXXBBN-DEOSSOPVSA-N docosyl (2S)-2-aminopropanoate Chemical compound CCCCCCCCCCCCCCCCCCCCCCOC(=O)[C@H](C)N RNJZAOHMJXXBBN-DEOSSOPVSA-N 0.000 description 1
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
- DWHHIPIOLSXJLV-AWEZNQCLSA-N dodecyl (2s)-2-aminopropanoate Chemical compound CCCCCCCCCCCCOC(=O)[C@H](C)N DWHHIPIOLSXJLV-AWEZNQCLSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N heptadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- UCCMBYBOOAOUMZ-SFHVURJKSA-N hexadecyl (2s)-2-aminopropanoate Chemical compound CCCCCCCCCCCCCCCCOC(=O)[C@H](C)N UCCMBYBOOAOUMZ-SFHVURJKSA-N 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 125000002960 margaryl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- REIUXOLGHVXAEO-UHFFFAOYSA-N pentadecan-1-ol Chemical compound CCCCCCCCCCCCCCCO REIUXOLGHVXAEO-UHFFFAOYSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- OGRCQGKJWFJROA-INIZCTEOSA-N tetradecyl (2s)-2-aminopropanoate Chemical compound CCCCCCCCCCCCCCOC(=O)[C@H](C)N OGRCQGKJWFJROA-INIZCTEOSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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| US202062993300P | 2020-03-23 | 2020-03-23 | |
| US62/993,300 | 2020-03-23 | ||
| PCT/US2021/022880 WO2021194828A1 (en) | 2020-03-23 | 2021-03-18 | Compounds useful in hiv therapy |
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| JP2023518851A JP2023518851A (ja) | 2023-05-08 |
| JPWO2021194828A5 true JPWO2021194828A5 (de) | 2024-03-29 |
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| JP2022557823A Pending JP2023518851A (ja) | 2020-03-23 | 2021-03-18 | Ｈｉｖ治療に有用な化合物 |
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| US (1) | US20230151049A1 (de) |
| EP (1) | EP4126888A1 (de) |
| JP (1) | JP2023518851A (de) |
| WO (1) | WO2021194828A1 (de) |
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| EP4358968A1 (de) * | 2021-06-22 | 2024-05-01 | Rome Therapeutics, Inc. | 4-ethinyl-3-hydroxy-tetrahydrofuranyl-adeninphosphoramidate und verwandte verbindungen und ihre verwendung bei der behandlung von medizinischen erkrankungen |
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| WO2013187978A1 (en) * | 2012-06-16 | 2013-12-19 | Nanjing Molecular Research, Inc. | Double-liver-targeting phosphoramidate and phosphonoamidate prodrugs |
| CN107286190A (zh) * | 2016-04-13 | 2017-10-24 | 刘沛 | 核苷之烃氧基苄基氨基磷酸/膦酸酯衍生物的制备及其医药用途 |
| CA3087192A1 (en) * | 2017-12-27 | 2019-07-04 | Raymond F. Schinazi | Combined modalities for nucleosides and/or nadph oxidase (nox) inhibitors as myeloid-specific antiviral agents |
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- 2021-03-18 WO PCT/US2021/022880 patent/WO2021194828A1/en unknown
- 2021-03-18 EP EP21721244.8A patent/EP4126888A1/de active Pending
- 2021-03-18 JP JP2022557823A patent/JP2023518851A/ja active Pending
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