OA12049A - Amino substituted pyrazoloÄ1,5,-aÜ-1,5-pyrimidinesand pyrazoloÄ1,5,-aÜ-1,3,5-triazines. - Google Patents

Info

Publication number

OA12049A

OA12049A OA1200200088A OA1200200088A OA12049A OA 12049 A OA12049 A OA 12049A OA 1200200088 A OA1200200088 A OA 1200200088A OA 1200200088 A OA1200200088 A OA 1200200088A OA 12049 A OA12049 A OA 12049A

Authority

OA

OAPI

Prior art keywords

alkyl

cycloalkyl

compound

nr8r9

aryl

Prior art date

1999-09-30

Links

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• 125000003277 amino group Chemical group 0.000 title description 7
• 150000001875 compounds Chemical class 0.000 claims abstract description 240
• 108020003175 receptors Proteins 0.000 claims abstract description 72
• 102000005962 receptors Human genes 0.000 claims abstract description 72
• 230000027455 binding Effects 0.000 claims abstract description 45
• 238000000034 method Methods 0.000 claims abstract description 38
• 238000003556 assay Methods 0.000 claims abstract description 24
• 101150027439 NPY1 gene Proteins 0.000 claims abstract description 22
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
• 208000035475 disorder Diseases 0.000 claims abstract description 11
• 208000019454 Feeding and Eating disease Diseases 0.000 claims abstract description 9
• 208000030814 Eating disease Diseases 0.000 claims abstract description 8
• 235000014632 disordered eating Nutrition 0.000 claims abstract description 7
• 206010020772 Hypertension Diseases 0.000 claims abstract description 4
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 142
• 125000000217 alkyl group Chemical group 0.000 claims description 132
• -1 ethyl,isopropyl Chemical group 0.000 claims description 126
• 125000003118 aryl group Chemical group 0.000 claims description 49
• 125000001072 heteroaryl group Chemical group 0.000 claims description 44
• 229910052799 carbon Inorganic materials 0.000 claims description 43
• 101710151321 Melanostatin Proteins 0.000 claims description 41
• 229910052736 halogen Inorganic materials 0.000 claims description 40
• 150000002367 halogens Chemical class 0.000 claims description 39
• 125000001188 haloalkyl group Chemical group 0.000 claims description 38
• 239000000203 mixture Substances 0.000 claims description 38
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 30
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 26
• 239000003795 chemical substances by application Substances 0.000 claims description 24
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 23
• 125000003342 alkenyl group Chemical group 0.000 claims description 20
• 210000004027 cell Anatomy 0.000 claims description 20
• 229910052739 hydrogen Inorganic materials 0.000 claims description 20
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 17
• 239000000651 prodrug Substances 0.000 claims description 17
• 229940002612 prodrug Drugs 0.000 claims description 17
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 15
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 15
• 238000000338 in vitro Methods 0.000 claims description 13
• 125000004429 atom Chemical group 0.000 claims description 12
• 239000003937 drug carrier Substances 0.000 claims description 12
• 125000005843 halogen group Chemical group 0.000 claims description 12
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
• 150000001721 carbon Chemical group 0.000 claims description 11
• 230000000694 effects Effects 0.000 claims description 11
• 125000000623 heterocyclic group Chemical group 0.000 claims description 11
• 239000003981 vehicle Substances 0.000 claims description 11
• 108091005471 CRHR1 Proteins 0.000 claims description 10
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 10
• 125000000304 alkynyl group Chemical group 0.000 claims description 10
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 9
• 125000003435 aroyl group Chemical group 0.000 claims description 9
• 125000001589 carboacyl group Chemical group 0.000 claims description 9
• 239000003085 diluting agent Substances 0.000 claims description 9
• 239000000556 agonist Substances 0.000 claims description 8
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 8
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 8
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 7
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
• 125000001424 substituent group Chemical group 0.000 claims description 7
• 125000005143 heteroarylsulfonyl group Chemical group 0.000 claims description 6
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 6
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
• 208000008589 Obesity Diseases 0.000 claims description 4
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 4
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
• 239000001257 hydrogen Substances 0.000 claims description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
• 230000002401 inhibitory effect Effects 0.000 claims description 4
• 239000002660 neuropeptide Y receptor antagonist Substances 0.000 claims description 4
• 235000020824 obesity Nutrition 0.000 claims description 4
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 3
• 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 3
• 206010006550 Bulimia nervosa Diseases 0.000 claims description 3
• 102000004877 Insulin Human genes 0.000 claims description 3
• 108090001061 Insulin Proteins 0.000 claims description 3
• 201000010099 disease Diseases 0.000 claims description 3
• 239000002552 dosage form Substances 0.000 claims description 3
• 230000020595 eating behavior Effects 0.000 claims description 3
• 229940125396 insulin Drugs 0.000 claims description 3
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
• 230000000929 thyromimetic effect Effects 0.000 claims description 3
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 2
• 229910052801 chlorine Inorganic materials 0.000 claims description 2
• 125000004427 diamine group Chemical group 0.000 claims description 2
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
• 239000008024 pharmaceutical diluent Substances 0.000 claims description 2
• 238000005406 washing Methods 0.000 claims description 2
• SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical group [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 2
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims 2
• XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 claims 1
• ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims 1
• ROJNYKZWTOHRNU-UHFFFAOYSA-N 2-chloro-4,5-difluoro-n-[[2-methoxy-5-(methylcarbamoylamino)phenyl]carbamoyl]benzamide Chemical compound CNC(=O)NC1=CC=C(OC)C(NC(=O)NC(=O)C=2C(=CC(F)=C(F)C=2)Cl)=C1 ROJNYKZWTOHRNU-UHFFFAOYSA-N 0.000 claims 1
• NKOHRVBBQISBSB-UHFFFAOYSA-N 5-[(4-hydroxyphenyl)methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1=CC(O)=CC=C1CC1C(=O)NC(=O)S1 NKOHRVBBQISBSB-UHFFFAOYSA-N 0.000 claims 1
• 208000000044 Amnesia Diseases 0.000 claims 1
• 208000019901 Anxiety disease Diseases 0.000 claims 1
• 206010007559 Cardiac failure congestive Diseases 0.000 claims 1
• RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 claims 1
• 206010010904 Convulsion Diseases 0.000 claims 1
• 206010012735 Diarrhoea Diseases 0.000 claims 1
• 101100440695 Dictyostelium discoideum corB gene Proteins 0.000 claims 1
• 206010019280 Heart failures Diseases 0.000 claims 1
• 208000026139 Memory disease Diseases 0.000 claims 1
• 208000019695 Migraine disease Diseases 0.000 claims 1
• 206010028735 Nasal congestion Diseases 0.000 claims 1
• 208000002193 Pain Diseases 0.000 claims 1
• 229940123934 Reductase inhibitor Drugs 0.000 claims 1
• 229940123659 Sorbitol dehydrogenase inhibitor Drugs 0.000 claims 1
• 229940100389 Sulfonylurea Drugs 0.000 claims 1
• 229940123464 Thiazolidinedione Drugs 0.000 claims 1
• 229960002632 acarbose Drugs 0.000 claims 1
• XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 claims 1
• IMHBYKMAHXWHRP-UHFFFAOYSA-N anilazine Chemical compound ClC1=CC=CC=C1NC1=NC(Cl)=NC(Cl)=N1 IMHBYKMAHXWHRP-UHFFFAOYSA-N 0.000 claims 1
• 230000036506 anxiety Effects 0.000 claims 1
• 229960001761 chlorpropamide Drugs 0.000 claims 1
• 229960004580 glibenclamide Drugs 0.000 claims 1
• ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 claims 1
• 230000006984 memory degeneration Effects 0.000 claims 1
• 208000023060 memory loss Diseases 0.000 claims 1
• XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims 1
• 229960003105 metformin Drugs 0.000 claims 1
• 206010027599 migraine Diseases 0.000 claims 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
• 230000001850 reproductive effect Effects 0.000 claims 1
• 230000001568 sexual effect Effects 0.000 claims 1
• 230000035939 shock Effects 0.000 claims 1
• 208000019116 sleep disease Diseases 0.000 claims 1
• YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims 1
• 230000001225 therapeutic effect Effects 0.000 claims 1
• GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 claims 1
• 229960001641 troglitazone Drugs 0.000 claims 1
• 239000000523 sample Substances 0.000 abstract description 9
• 230000002093 peripheral effect Effects 0.000 abstract description 3
• 208000015114 central nervous system disease Diseases 0.000 abstract description 2
• 230000004807 localization Effects 0.000 abstract 2
• 208000030159 metabolic disease Diseases 0.000 abstract 1
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 65
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 59
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
• 239000003513 alkali Substances 0.000 description 55
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 54
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 43
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 41
• 238000003756 stirring Methods 0.000 description 39
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 38
• 238000006243 chemical reaction Methods 0.000 description 38
• 239000003921 oil Substances 0.000 description 35
• 235000019198 oils Nutrition 0.000 description 35
• 239000012442 inert solvent Substances 0.000 description 34
• 239000000243 solution Substances 0.000 description 34
• 102400000064 Neuropeptide Y Human genes 0.000 description 33
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 26
• 235000019439 ethyl acetate Nutrition 0.000 description 26
• 239000010410 layer Substances 0.000 description 25
• 239000007787 solid Substances 0.000 description 25
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 22
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
• 239000002585 base Substances 0.000 description 21
• 239000000284 extract Substances 0.000 description 21
• URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 description 21
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
• 230000002829 reductive effect Effects 0.000 description 19
• 125000004432 carbon atom Chemical group C* 0.000 description 18
• 150000004292 cyclic ethers Chemical class 0.000 description 18
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 17
• 239000012141 concentrate Substances 0.000 description 17
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 16
• 150000001983 dialkylethers Chemical class 0.000 description 16
• 238000010992 reflux Methods 0.000 description 16
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 16
• 235000008504 concentrate Nutrition 0.000 description 15
• 150000004678 hydrides Chemical class 0.000 description 15
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 14
• 239000007832 Na2SO4 Substances 0.000 description 13
• 239000002253 acid Substances 0.000 description 13
• 150000003950 cyclic amides Chemical class 0.000 description 13
• 239000000047 product Substances 0.000 description 13
• 229910052938 sodium sulfate Inorganic materials 0.000 description 13
• 235000011152 sodium sulphate Nutrition 0.000 description 13
• 238000004809 thin layer chromatography Methods 0.000 description 13
• 125000003545 alkoxy group Chemical group 0.000 description 12
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 12
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 12
• 239000012044 organic layer Substances 0.000 description 12
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
• 150000008064 anhydrides Chemical class 0.000 description 11
• 229960004132 diethyl ether Drugs 0.000 description 11
• 239000003480 eluent Substances 0.000 description 11
• 238000000746 purification Methods 0.000 description 11
• 229920006395 saturated elastomer Polymers 0.000 description 11
• 125000005270 trialkylamine group Chemical group 0.000 description 11
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 10
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 10
• 125000005233 alkylalcohol group Chemical group 0.000 description 10
• 150000001408 amides Chemical class 0.000 description 10
• 229940113088 dimethylacetamide Drugs 0.000 description 10
• 239000011734 sodium Substances 0.000 description 10
• 229910052708 sodium Inorganic materials 0.000 description 10
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 9
• QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 9
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 9
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
• 229960000583 acetic acid Drugs 0.000 description 9
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 9
• 239000003814 drug Substances 0.000 description 9
• 239000012528 membrane Substances 0.000 description 9
• 239000000546 pharmaceutical excipient Substances 0.000 description 9
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