BRPI0710919A2 - derivados de diceto-piperazina e piperidina como agentes antivirais - Google Patents

Info

Publication number

BRPI0710919A2

BRPI0710919A2 BRPI0710919-9A BRPI0710919A BRPI0710919A2 BR PI0710919 A2 BRPI0710919 A2 BR PI0710919A2 BR PI0710919 A BRPI0710919 A BR PI0710919A BR PI0710919 A2 BRPI0710919 A2 BR PI0710919A2

Authority

BR

Brazil

Prior art keywords

formula

original document

see original

document page

group

Prior art date

2006-04-25

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• 239000003443 antiviral agent Substances 0.000 title claims description 8
• 150000003053 piperidines Chemical class 0.000 title description 3
• BXRNXXXXHLBUKK-UHFFFAOYSA-N piperazine-2,5-dione Chemical compound O=C1CNC(=O)CN1 BXRNXXXXHLBUKK-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 203
• 238000000034 method Methods 0.000 claims abstract description 130
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims abstract description 77
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims abstract description 42
• 208000030507 AIDS Diseases 0.000 claims abstract description 21
• 239000003795 chemical substances by application Substances 0.000 claims abstract description 18
• 230000000840 anti-viral effect Effects 0.000 claims abstract description 16
• 238000011282 treatment Methods 0.000 claims abstract description 15
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
• 239000000203 mixture Substances 0.000 claims description 235
• -1 cyano, hydroxy Chemical group 0.000 claims description 225
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 94
• 125000001072 heteroaryl group Chemical group 0.000 claims description 76
• 125000003118 aryl group Chemical group 0.000 claims description 59
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 51
• 125000000217 alkyl group Chemical group 0.000 claims description 49
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 44
• 229910052736 halogen Inorganic materials 0.000 claims description 41
• 150000002367 halogens Chemical class 0.000 claims description 41
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 39
• 229910052739 hydrogen Inorganic materials 0.000 claims description 39
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 38
• 239000001257 hydrogen Substances 0.000 claims description 33
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 31
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 26
• 125000002950 monocyclic group Chemical group 0.000 claims description 26
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 24
• 229910052757 nitrogen Inorganic materials 0.000 claims description 24
• 125000005842 heteroatom Chemical group 0.000 claims description 22
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
• 150000003839 salts Chemical class 0.000 claims description 20
• 125000001424 substituent group Chemical group 0.000 claims description 18
• 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims description 16
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 14
• 125000006413 ring segment Chemical group 0.000 claims description 14
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 13
• XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims description 13
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 13
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 12
• 125000004104 aryloxy group Chemical group 0.000 claims description 12
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 12
• 125000002619 bicyclic group Chemical group 0.000 claims description 11
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 10
• 150000002431 hydrogen Chemical group 0.000 claims description 10
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 10
• 125000004429 atom Chemical group 0.000 claims description 9
• 239000002835 hiv fusion inhibitor Substances 0.000 claims description 9
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 9
• 208000031886 HIV Infections Diseases 0.000 claims description 8
• 208000037357 HIV infectious disease Diseases 0.000 claims description 8
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
• 125000004122 cyclic group Chemical group 0.000 claims description 8
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 8
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 8
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
• 239000003085 diluting agent Substances 0.000 claims description 7
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Natural products C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 6
• 241000700605 Viruses Species 0.000 claims description 6
• 230000002924 anti-infective effect Effects 0.000 claims description 6
• 239000002955 immunomodulating agent Substances 0.000 claims description 6
• 229940121354 immunomodulator Drugs 0.000 claims description 6
• 125000004043 oxo group Chemical group O=* 0.000 claims description 6
• 125000005309 thioalkoxy group Chemical group 0.000 claims description 6
• 241000124008 Mammalia Species 0.000 claims description 5
• 125000000304 alkynyl group Chemical group 0.000 claims description 5
• 230000000694 effects Effects 0.000 claims description 5
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 5
• 125000002883 imidazolyl group Chemical group 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
• 229910052717 sulfur Inorganic materials 0.000 claims description 5
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 4
• 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 4
• 239000000969 carrier Substances 0.000 claims description 4
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
• 230000002584 immunomodulator Effects 0.000 claims description 4
• 239000012678 infectious agent Substances 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• 125000004076 pyridyl group Chemical group 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
• 125000002541 furyl group Chemical group 0.000 claims description 3
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 3
• 125000001624 naphthyl group Chemical group 0.000 claims description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
• 125000002971 oxazolyl group Chemical group 0.000 claims description 3
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 3
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
• 229940124530 sulfonamide Drugs 0.000 claims description 3
• 150000003456 sulfonamides Chemical class 0.000 claims description 3
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
• 125000000335 thiazolyl group Chemical group 0.000 claims description 3
• 125000001544 thienyl group Chemical group 0.000 claims description 3
• 125000001425 triazolyl group Chemical group 0.000 claims description 3
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
• 229910003827 NRaRb Inorganic materials 0.000 claims description 2
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 2
• 230000036436 anti-hiv Effects 0.000 claims description 2
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 2
• 229910052705 radium Inorganic materials 0.000 claims description 2
• 229910052701 rubidium Inorganic materials 0.000 claims description 2
• 125000003226 pyrazolyl group Chemical group 0.000 claims 2
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 1
• 229940126154 HIV entry inhibitor Drugs 0.000 claims 1
• 102220493743 HLA class II histocompatibility antigen, DRB1 beta chain_R42G_mutation Human genes 0.000 claims 1
• 240000007817 Olea europaea Species 0.000 claims 1
• 229940079593 drug Drugs 0.000 abstract description 10
• 239000003814 drug Substances 0.000 abstract description 10
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 435
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 360
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 319
• 239000011541 reaction mixture Substances 0.000 description 183
• 238000005160 1H NMR spectroscopy Methods 0.000 description 168
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 168
• 239000007787 solid Substances 0.000 description 160
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 147
• 239000000243 solution Substances 0.000 description 147
• 238000002360 preparation method Methods 0.000 description 132
• 230000002829 reductive effect Effects 0.000 description 128
• 235000019439 ethyl acetate Nutrition 0.000 description 118
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 112
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 106
• 239000012044 organic layer Substances 0.000 description 106
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 99
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 97
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 80
• 238000006243 chemical reaction Methods 0.000 description 80
• 239000003480 eluent Substances 0.000 description 78
• 239000002904 solvent Substances 0.000 description 72
• 238000004440 column chromatography Methods 0.000 description 70
• 230000014759 maintenance of location Effects 0.000 description 69
• 239000012267 brine Substances 0.000 description 66
• 238000002953 preparative HPLC Methods 0.000 description 66
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 66
• 239000011734 sodium Substances 0.000 description 64
• 239000003039 volatile agent Substances 0.000 description 56
• CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 54
• 239000012317 TBTU Substances 0.000 description 53
• 239000003921 oil Substances 0.000 description 53
• 238000004128 high performance liquid chromatography Methods 0.000 description 52
• 238000000746 purification Methods 0.000 description 52
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 50
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 50
• 235000017557 sodium bicarbonate Nutrition 0.000 description 50
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 48
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 47
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
• 239000000047 product Substances 0.000 description 41
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 40
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 40
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 35
• 239000002253 acid Substances 0.000 description 34
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 32
• 150000001412 amines Chemical class 0.000 description 32
• 229920006395 saturated elastomer Polymers 0.000 description 32
• 238000010898 silica gel chromatography Methods 0.000 description 29
• OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 28
• 238000003756 stirring Methods 0.000 description 27
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
• 239000012043 crude product Substances 0.000 description 25
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 25
• 229910000104 sodium hydride Inorganic materials 0.000 description 24
• 239000000460 chlorine Substances 0.000 description 23
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 23
• 239000000543 intermediate Substances 0.000 description 23
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
• 239000002585 base Substances 0.000 description 21
• 229910052796 boron Inorganic materials 0.000 description 21
• 239000000706 filtrate Substances 0.000 description 21
• HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 21
• 238000005481 NMR spectroscopy Methods 0.000 description 20
• 238000001704 evaporation Methods 0.000 description 20
• 230000008020 evaporation Effects 0.000 description 20
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 20
• 235000019341 magnesium sulphate Nutrition 0.000 description 20
• 239000012071 phase Substances 0.000 description 20
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 20
• LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 19
• 230000002441 reversible effect Effects 0.000 description 19
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
• 239000012265 solid product Substances 0.000 description 18
• 229960002555 zidovudine Drugs 0.000 description 18
• VTURGTOHORWCLD-UHFFFAOYSA-N 2-[4-fluoro-7-(triazol-1-yl)-1h-pyrrolo[2,3-c]pyridin-3-yl]-2-oxoacetic acid Chemical compound N1=CC(F)=C2C(C(=O)C(=O)O)=CNC2=C1N1C=CN=N1 VTURGTOHORWCLD-UHFFFAOYSA-N 0.000 description 17
• 239000003112 inhibitor Substances 0.000 description 17
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 16
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
• 239000012312 sodium hydride Substances 0.000 description 16
• WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 15
• 239000010410 layer Substances 0.000 description 15
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• 238000001914 filtration Methods 0.000 description 14
• 239000008107 starch Substances 0.000 description 14
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
• 241000725303 Human immunodeficiency virus Species 0.000 description 13
• 239000007788 liquid Substances 0.000 description 13
• 239000012299 nitrogen atmosphere Substances 0.000 description 13
• QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 description 13
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• 238000001816 cooling Methods 0.000 description 12
• 229940086542 triethylamine Drugs 0.000 description 12
• XTYSXGHMTNTKFH-BDEHJDMKSA-N (2s)-1-[(2s,4r)-4-benzyl-2-hydroxy-5-[[(1s,2r)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]amino]-5-oxopentyl]-n-tert-butyl-4-(pyridin-3-ylmethyl)piperazine-2-carboxamide;hydrate Chemical compound O.C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 XTYSXGHMTNTKFH-BDEHJDMKSA-N 0.000 description 11
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 11
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• 238000010438 heat treatment Methods 0.000 description 11
• 229960001936 indinavir Drugs 0.000 description 11
• 238000010992 reflux Methods 0.000 description 11
• VGTAXUWLRKSWSD-UHFFFAOYSA-N 1-(7-bromo-4-fluoro-1h-pyrrolo[2,3-c]pyridin-3-yl)-2-[4-(1-phenyltetrazol-5-yl)piperazin-1-yl]ethane-1,2-dione Chemical compound C1=2C(F)=CN=C(Br)C=2NC=C1C(=O)C(=O)N(CC1)CCN1C1=NN=NN1C1=CC=CC=C1 VGTAXUWLRKSWSD-UHFFFAOYSA-N 0.000 description 10
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• 238000004811 liquid chromatography Methods 0.000 description 10
• 239000000126 substance Substances 0.000 description 10
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• 125000004432 carbon atom Chemical group C* 0.000 description 9
• 229910002091 carbon monoxide Inorganic materials 0.000 description 9
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 9
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• 125000003545 alkoxy group Chemical group 0.000 description 8
• 150000001408 amides Chemical class 0.000 description 8
• 229910052799 carbon Inorganic materials 0.000 description 8
• 239000003153 chemical reaction reagent Substances 0.000 description 8
• AJDPNPAGZMZOMN-UHFFFAOYSA-N diethyl (4-oxo-1,2,3-benzotriazin-3-yl) phosphate Chemical compound C1=CC=C2C(=O)N(OP(=O)(OCC)OCC)N=NC2=C1 AJDPNPAGZMZOMN-UHFFFAOYSA-N 0.000 description 8
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
• UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 8
• 229910000027 potassium carbonate Inorganic materials 0.000 description 8
• 239000002244 precipitate Substances 0.000 description 8
• 239000000725 suspension Substances 0.000 description 8
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