KR20230164602A

KR20230164602A - 다이아실글리세롤 키나아제 저해제로서 헤테로사이클 화합물 및 이의 용도

다이아실글리세롤 키나아제 저해제로서 헤테로사이클 화합물 및 이의 용도 Download PDF

Info

Publication number: KR20230164602A
Authority: KR; South Korea
Prior art keywords: methyl; dihydropyrido; piperidin; pyrazine; chloro
Prior art date: 2022-05-25

Application number

KR1020230067103A

Other languages

English (en)

Korean (ko)

Inventor

윤수영

장창영

김병규

김윤영

김형진

정세환

곽영신

최민호

Original Assignee

주식회사 엘지화학

Priority date

2022-05-25

Filing date

2023-05-24

Publication date

2023-12-04

2023-05-24 Application filed by 주식회사 엘지화학 filed Critical 주식회사 엘지화학

2023-12-04 Publication of KR20230164602A publication Critical patent/KR20230164602A/ko

Links

150000002391 heterocyclic compounds Chemical class 0.000 title abstract description 3
239000003112 inhibitor Substances 0.000 title description 3
108091000080 Phosphotransferase Proteins 0.000 title description 2
102000020233 phosphotransferase Human genes 0.000 title description 2
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
239000004480 active ingredient Substances 0.000 claims abstract description 6
-1 cyano, carboxy Chemical group 0.000 claims description 748
150000001875 compounds Chemical class 0.000 claims description 410
125000000217 alkyl group Chemical group 0.000 claims description 184
ZYOYYQRWXITKFF-UHFFFAOYSA-N pyrazine-2,3-dione Chemical compound O=C1N=CC=NC1=O ZYOYYQRWXITKFF-UHFFFAOYSA-N 0.000 claims description 177
XVIAPHVAGFEFFN-UHFFFAOYSA-N pyrimidine-5-carbonitrile Chemical compound N#CC1=CN=CN=C1 XVIAPHVAGFEFFN-UHFFFAOYSA-N 0.000 claims description 74
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 57
229920006395 saturated elastomer Polymers 0.000 claims description 46
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 33
238000000034 method Methods 0.000 claims description 32
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 30
125000000623 heterocyclic group Chemical group 0.000 claims description 29
125000005843 halogen group Chemical group 0.000 claims description 28
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 24
125000004103 aminoalkyl group Chemical group 0.000 claims description 24
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
125000003545 alkoxy group Chemical group 0.000 claims description 21
GZPHSAQLYPIAIN-UHFFFAOYSA-N 3-pyridinecarbonitrile Chemical compound N#CC1=CC=CN=C1 GZPHSAQLYPIAIN-UHFFFAOYSA-N 0.000 claims description 20
108010062677 Diacylglycerol Kinase Proteins 0.000 claims description 19
125000004093 cyano group Chemical group *C#N 0.000 claims description 19
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 17
206010028980 Neoplasm Diseases 0.000 claims description 16
102000011107 Diacylglycerol Kinase Human genes 0.000 claims description 15
125000001424 substituent group Chemical group 0.000 claims description 15
125000003118 aryl group Chemical group 0.000 claims description 14
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
239000001257 hydrogen Substances 0.000 claims description 12
229910052739 hydrogen Inorganic materials 0.000 claims description 12
229940124530 sulfonamide Drugs 0.000 claims description 12
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 11
201000011510 cancer Diseases 0.000 claims description 11
125000000753 cycloalkyl group Chemical group 0.000 claims description 11
125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 11
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 10
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 10
125000005129 aryl carbonyl group Chemical group 0.000 claims description 10
201000010099 disease Diseases 0.000 claims description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
125000004438 haloalkoxy group Chemical group 0.000 claims description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 10
IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 claims description 10
NIRIGNIPEFMZHT-UHFFFAOYSA-N pyrimidine-5-sulfonamide Chemical compound NS(=O)(=O)C1=CN=CN=C1 NIRIGNIPEFMZHT-UHFFFAOYSA-N 0.000 claims description 10
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 8
125000001188 haloalkyl group Chemical group 0.000 claims description 8
MJBWDEQAUQTVKK-IAGOWNOFSA-N aflatoxin M1 Chemical compound C=1([C@]2(O)C=CO[C@@H]2OC=1C=C(C1=2)OC)C=2OC(=O)C2=C1CCC2=O MJBWDEQAUQTVKK-IAGOWNOFSA-N 0.000 claims description 7
125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
125000005842 heteroatom Chemical group 0.000 claims description 7
125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 7
125000000304 alkynyl group Chemical group 0.000 claims description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
125000004043 oxo group Chemical group O=* 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 5
125000005145 cycloalkylaminosulfonyl group Chemical group 0.000 claims description 5
125000004663 dialkyl amino group Chemical group 0.000 claims description 5
125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
229910052717 sulfur Inorganic materials 0.000 claims description 5
DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 claims description 4
XWXPRCDFFCVMNT-UHFFFAOYSA-N 1,3-thiazole-5-carbonitrile Chemical compound N#CC1=CN=CS1 XWXPRCDFFCVMNT-UHFFFAOYSA-N 0.000 claims description 4
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 4
125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 4
125000004429 atom Chemical group 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
PMSVVUSIPKHUMT-UHFFFAOYSA-N cyanopyrazine Chemical compound N#CC1=CN=CC=N1 PMSVVUSIPKHUMT-UHFFFAOYSA-N 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
PJESVVYWPFAJCS-UHFFFAOYSA-N pyridazine-3-carbonitrile Chemical compound N#CC1=CC=CN=N1 PJESVVYWPFAJCS-UHFFFAOYSA-N 0.000 claims description 4
IIHQNAXFIODVDU-UHFFFAOYSA-N pyrimidine-2-carbonitrile Chemical compound N#CC1=NC=CC=N1 IIHQNAXFIODVDU-UHFFFAOYSA-N 0.000 claims description 4
239000011593 sulfur Substances 0.000 claims description 4
125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims description 3
125000005084 alkoxyalkylaminoalkyl group Chemical group 0.000 claims description 3
125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 3
125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 3
125000003710 aryl alkyl group Chemical group 0.000 claims description 3
125000005128 aryl amino alkyl group Chemical group 0.000 claims description 3
125000005605 benzo group Chemical group 0.000 claims description 3
125000004966 cyanoalkyl group Chemical group 0.000 claims description 3
125000004858 cycloalkoxyalkyl group Chemical group 0.000 claims description 3
125000004472 dialkylaminosulfonyl group Chemical group 0.000 claims description 3
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
125000005181 hydroxyalkylaminoalkyl group Chemical group 0.000 claims description 3
125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 3
206010005003 Bladder cancer Diseases 0.000 claims description 2
208000003174 Brain Neoplasms Diseases 0.000 claims description 2
206010006187 Breast cancer Diseases 0.000 claims description 2
208000026310 Breast neoplasm Diseases 0.000 claims description 2
206010008342 Cervix carcinoma Diseases 0.000 claims description 2
206010009944 Colon cancer Diseases 0.000 claims description 2
206010014733 Endometrial cancer Diseases 0.000 claims description 2
206010014759 Endometrial neoplasm Diseases 0.000 claims description 2
208000000461 Esophageal Neoplasms Diseases 0.000 claims description 2
206010017993 Gastrointestinal neoplasms Diseases 0.000 claims description 2
208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
206010023825 Laryngeal cancer Diseases 0.000 claims description 2
206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
206010029260 Neuroblastoma Diseases 0.000 claims description 2
206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
206010033128 Ovarian cancer Diseases 0.000 claims description 2
206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
206010060862 Prostate cancer Diseases 0.000 claims description 2
208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
206010038389 Renal cancer Diseases 0.000 claims description 2
201000000582 Retinoblastoma Diseases 0.000 claims description 2
208000000453 Skin Neoplasms Diseases 0.000 claims description 2
208000024313 Testicular Neoplasms Diseases 0.000 claims description 2
206010057644 Testis cancer Diseases 0.000 claims description 2
208000024770 Thyroid neoplasm Diseases 0.000 claims description 2
208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
201000010881 cervical cancer Diseases 0.000 claims description 2
208000029742 colonic neoplasm Diseases 0.000 claims description 2
125000005357 cycloalkylalkynyl group Chemical group 0.000 claims description 2
201000004101 esophageal cancer Diseases 0.000 claims description 2
201000010982 kidney cancer Diseases 0.000 claims description 2
206010023841 laryngeal neoplasm Diseases 0.000 claims description 2
201000007270 liver cancer Diseases 0.000 claims description 2
208000014018 liver neoplasm Diseases 0.000 claims description 2
201000005202 lung cancer Diseases 0.000 claims description 2
208000020816 lung neoplasm Diseases 0.000 claims description 2
208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
201000008968 osteosarcoma Diseases 0.000 claims description 2
201000002528 pancreatic cancer Diseases 0.000 claims description 2
208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
RSBWEDPLUWCPQX-UHFFFAOYSA-N pyrido[2,3-b]pyrazine-7-carboxamide Chemical compound NC(=O)c1cnc2nccnc2c1 RSBWEDPLUWCPQX-UHFFFAOYSA-N 0.000 claims description 2
201000000849 skin cancer Diseases 0.000 claims description 2
201000003120 testicular cancer Diseases 0.000 claims description 2
201000002510 thyroid cancer Diseases 0.000 claims description 2
201000005112 urinary bladder cancer Diseases 0.000 claims description 2
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 4
230000000694 effects Effects 0.000 abstract description 8
229940123948 Diacylglycerol kinase inhibitor Drugs 0.000 abstract description 3
239000003047 diacylglycerol kinase inhibitor Substances 0.000 abstract description 3
238000002360 preparation method Methods 0.000 description 586
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 340
238000005160 1H NMR spectroscopy Methods 0.000 description 316
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 238
RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 136
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
239000011734 sodium Substances 0.000 description 108
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 75
QYIUJCTWKIOECG-UHFFFAOYSA-N CN(C1=C(N(C2CCNCC2)C2=O)N=CC(Cl)=C1)C2=O Chemical compound CN(C1=C(N(C2CCNCC2)C2=O)N=CC(Cl)=C1)C2=O QYIUJCTWKIOECG-UHFFFAOYSA-N 0.000 description 71
FREJAOSUHFGDBW-UHFFFAOYSA-N pyrimidine-5-carbaldehyde Chemical compound O=CC1=CN=CN=C1 FREJAOSUHFGDBW-UHFFFAOYSA-N 0.000 description 69
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 60
239000000203 mixture Substances 0.000 description 58
238000003820 Medium-pressure liquid chromatography Methods 0.000 description 54
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
239000012044 organic layer Substances 0.000 description 51
239000011541 reaction mixture Substances 0.000 description 48
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 43
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 42
238000004519 manufacturing process Methods 0.000 description 39
239000000243 solution Substances 0.000 description 39
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
238000006243 chemical reaction Methods 0.000 description 32
DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 28
SSIJZDYQYMMISZ-UHFFFAOYSA-N CN(C1=C(N(C2CCNCC2)C2=O)N=CC(F)=C1)C2=O Chemical compound CN(C1=C(N(C2CCNCC2)C2=O)N=CC(F)=C1)C2=O SSIJZDYQYMMISZ-UHFFFAOYSA-N 0.000 description 26
FXQSUQZXESNFNH-UHFFFAOYSA-N 2-chloropyrimidine-5-carbonitrile Chemical compound ClC1=NC=C(C#N)C=N1 FXQSUQZXESNFNH-UHFFFAOYSA-N 0.000 description 25
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 24
239000012267 brine Substances 0.000 description 22
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 22
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
235000019439 ethyl acetate Nutrition 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 20
QDXGKRWDQCEABB-UHFFFAOYSA-N pyrimidine-5-carboxamide Chemical compound NC(=O)C1=CN=CN=C1 QDXGKRWDQCEABB-UHFFFAOYSA-N 0.000 description 17
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 16
238000004821 distillation Methods 0.000 description 16
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 16
YSBGFMCKYPFGTM-UHFFFAOYSA-N pyrido[2,3-b]pyrazine-2,3-dione Chemical compound C1=CC=NC2=NC(=O)C(=O)N=C21 YSBGFMCKYPFGTM-UHFFFAOYSA-N 0.000 description 16
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
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YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 14
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
210000001744 T-lymphocyte Anatomy 0.000 description 13
239000007864 aqueous solution Substances 0.000 description 12
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
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IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
238000000746 purification Methods 0.000 description 9
CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 9
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 8
239000000460 chlorine Substances 0.000 description 8
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 7
239000012153 distilled water Substances 0.000 description 7
229910000027 potassium carbonate Inorganic materials 0.000 description 7
XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 7
DUCXUPKLVVSJKA-UHFFFAOYSA-N 2-chloropyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=C(Cl)N=C1 DUCXUPKLVVSJKA-UHFFFAOYSA-N 0.000 description 6
DMAOAJYJIATWJS-UHFFFAOYSA-N 2-chloropyrimidine-5-sulfonyl chloride Chemical compound ClC1=NC=C(S(Cl)(=O)=O)C=N1 DMAOAJYJIATWJS-UHFFFAOYSA-N 0.000 description 6
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
238000001816 cooling Methods 0.000 description 6
229910001873 dinitrogen Inorganic materials 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
LJYQVOPFBNMTKJ-UHFFFAOYSA-N 2-chloropyrimidine-5-carbaldehyde Chemical compound ClC1=NC=C(C=O)C=N1 LJYQVOPFBNMTKJ-UHFFFAOYSA-N 0.000 description 5
BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 5
235000011054 acetic acid Nutrition 0.000 description 5
235000019270 ammonium chloride Nutrition 0.000 description 5
150000007942 carboxylates Chemical class 0.000 description 5
210000004027 cell Anatomy 0.000 description 5
239000003085 diluting agent Substances 0.000 description 5
238000000605 extraction Methods 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
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