CA2494700C - Calcium receptor modulating compound and use thereof - Google Patents

Info

Publication number

CA2494700C

CA2494700C CA2494700A CA2494700A CA2494700C CA 2494700 C CA2494700 C CA 2494700C CA 2494700 A CA2494700 A CA 2494700A CA 2494700 A CA2494700 A CA 2494700A CA 2494700 C CA2494700 C CA 2494700C

Authority

CA

Canada

Prior art keywords

group

optionally substituted

pyrimidine

phenyl

carboxamide

Prior art date

2002-08-26

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.)

Expired - Lifetime

Links

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• Global Dossier
• CIPO
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• 150000001875 compounds Chemical class 0.000 title claims abstract description 235
• 102000013830 Calcium-Sensing Receptors Human genes 0.000 title abstract description 8
• 108010050543 Calcium-Sensing Receptors Proteins 0.000 title abstract description 8
• 150000003839 salts Chemical class 0.000 claims abstract description 96
• 239000003814 drug Substances 0.000 claims description 27
• 208000001132 Osteoporosis Diseases 0.000 claims description 11
• 208000020084 Bone disease Diseases 0.000 claims description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 4
• BXHRVRKLOIWLRF-UHFFFAOYSA-N (2,2-diethyl-4-methoxypyrrolidin-1-yl)-(7,7-dimethyl-5-phenyl-5,6-dihydro-4H-pyrazolo[1,5-a]pyrimidin-3-yl)methanone Chemical compound CCC1(CC)CC(OC)CN1C(=O)C1=C(NC(CC2(C)C)C=3C=CC=CC=3)N2N=C1 BXHRVRKLOIWLRF-UHFFFAOYSA-N 0.000 claims description 3
• HVJNEZARBXRZAK-UHFFFAOYSA-N (2,2-diethyl-4-phenylmethoxypyrrolidin-1-yl)-(7,7-dimethyl-5-phenyl-5,6-dihydro-4H-pyrazolo[1,5-a]pyrimidin-3-yl)methanone Chemical compound CCC1(CC)CC(OCC=2C=CC=CC=2)CN1C(=O)C=1C=NN(C(C2)(C)C)C=1NC2C1=CC=CC=C1 HVJNEZARBXRZAK-UHFFFAOYSA-N 0.000 claims description 3
• XXVSBTZELNTIDQ-UHFFFAOYSA-N 2-[3-(4-methylphenyl)pentan-3-yl]-5-(2,7,7-trimethyl-5-phenyl-5,6-dihydro-4H-pyrazolo[1,5-a]pyrimidin-3-yl)-1,3,4-oxadiazole Chemical compound C=1C=C(C)C=CC=1C(CC)(CC)C(O1)=NN=C1C=1C(C)=NN(C(C2)(C)C)C=1NC2C1=CC=CC=C1 XXVSBTZELNTIDQ-UHFFFAOYSA-N 0.000 claims description 3
• KPGWORILVIXGJV-UHFFFAOYSA-N 2-[3-(4-methylphenyl)pentan-3-yl]-5-(2,7,7-trimethyl-5-phenyl-5,6-dihydro-4H-pyrazolo[1,5-a]pyrimidin-3-yl)-1,3,4-thiadiazole Chemical compound C=1C=C(C)C=CC=1C(CC)(CC)C(S1)=NN=C1C=1C(C)=NN(C(C2)(C)C)C=1NC2C1=CC=CC=C1 KPGWORILVIXGJV-UHFFFAOYSA-N 0.000 claims description 3
• RMLQZXDBDWLNLI-UHFFFAOYSA-N 5-(2-chlorophenyl)-2,7,7-trimethyl-N-[3-(4-methylphenyl)pentan-3-yl]-5,6-dihydro-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=1C=C(C)C=CC=1C(CC)(CC)NC(=O)C=1C(C)=NN(C(C2)(C)C)C=1NC2C1=CC=CC=C1Cl RMLQZXDBDWLNLI-UHFFFAOYSA-N 0.000 claims description 3
• SNDMCZNLIBQOCN-UHFFFAOYSA-N 5-(2-fluorophenyl)-2,7,7-trimethyl-N-(3-phenylpentan-3-yl)-5,6-dihydro-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=1C=CC=CC=1C(CC)(CC)NC(=O)C=1C(C)=NN(C(C2)(C)C)C=1NC2C1=CC=CC=C1F SNDMCZNLIBQOCN-UHFFFAOYSA-N 0.000 claims description 3
• GBSPWESAARMORA-UHFFFAOYSA-N 5-(2-fluorophenyl)-2,7,7-trimethyl-N-[3-(4-methylphenyl)pentan-3-yl]-5,6-dihydro-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=1C=C(C)C=CC=1C(CC)(CC)NC(=O)C=1C(C)=NN(C(C2)(C)C)C=1NC2C1=CC=CC=C1F GBSPWESAARMORA-UHFFFAOYSA-N 0.000 claims description 3
• UBDSIWCNQHLBBQ-UHFFFAOYSA-N 5-(2-fluorophenyl)-7,7-dimethyl-N-[3-(4-methylphenyl)pentan-3-yl]-5,6-dihydro-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=1C=C(C)C=CC=1C(CC)(CC)NC(=O)C=1C=NN(C(C2)(C)C)C=1NC2C1=CC=CC=C1F UBDSIWCNQHLBBQ-UHFFFAOYSA-N 0.000 claims description 3
• OIPLDJVAZJNLAZ-UHFFFAOYSA-N N-(3-ethylhexan-3-yl)-5-(2-fluorophenyl)-2,7,7-trimethyl-5,6-dihydro-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound CCCC(CC)(CC)NC(=O)C=1C(C)=NN(C(C2)(C)C)C=1NC2C1=CC=CC=C1F OIPLDJVAZJNLAZ-UHFFFAOYSA-N 0.000 claims description 3
• UEEHORXWFOHMHK-UHFFFAOYSA-N N-[3-(4-ethylphenyl)pentan-3-yl]-2,7,7-trimethyl-5-phenyl-5,6-dihydro-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=CC(CC)=CC=C1C(CC)(CC)NC(=O)C1=C(NC(CC2(C)C)C=3C=CC=CC=3)N2N=C1C UEEHORXWFOHMHK-UHFFFAOYSA-N 0.000 claims description 3
• ZWYZZYLXVBBARS-UHFFFAOYSA-N N-[3-(4-ethylphenyl)pentan-3-yl]-5-(2-fluorophenyl)-2,7,7-trimethyl-5,6-dihydro-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1=CC(CC)=CC=C1C(CC)(CC)NC(=O)C1=C(NC(CC2(C)C)C=3C(=CC=CC=3)F)N2N=C1C ZWYZZYLXVBBARS-UHFFFAOYSA-N 0.000 claims description 3
• LTXILEVHUFCFIX-UHFFFAOYSA-N N-[3-[4-(dimethylamino)phenyl]pentan-3-yl]-5-(2-fluorophenyl)-2,7,7-trimethyl-5,6-dihydro-4H-pyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C=1C=C(N(C)C)C=CC=1C(CC)(CC)NC(=O)C=1C(C)=NN(C(C2)(C)C)C=1NC2C1=CC=CC=C1F LTXILEVHUFCFIX-UHFFFAOYSA-N 0.000 claims description 3
• HUZMHENQDRSAGB-UHFFFAOYSA-N chembl1687946 Chemical compound C=1C=C(C)C=CC=1C(CC)(CC)NC(=O)C=1C=NN(C(C2)(C)C)C=1NC2C1=CC=CC=C1 HUZMHENQDRSAGB-UHFFFAOYSA-N 0.000 claims description 3
• QDXRZFVLYYUMGO-UHFFFAOYSA-N chembl1739914 Chemical compound C=1C=C(C)C=CC=1C(CC)(CC)NC(=O)C=1C(C)=NN(C(C2)(C)C)C=1NC2C1=CC=CC=C1 QDXRZFVLYYUMGO-UHFFFAOYSA-N 0.000 claims description 3
• CJKTUXMCNPTCQS-UHFFFAOYSA-N (2,2-diethyl-4-fluoropyrrolidin-1-yl)-(7,7-dimethyl-5-phenyl-5,6-dihydro-4H-pyrazolo[1,5-a]pyrimidin-3-yl)methanone Chemical compound CCC1(CC)CC(F)CN1C(=O)C1=C(NC(CC2(C)C)C=3C=CC=CC=3)N2N=C1 CJKTUXMCNPTCQS-UHFFFAOYSA-N 0.000 claims 2
• 230000002265 prevention Effects 0.000 claims 2
• 125000003341 7 membered heterocyclic group Chemical group 0.000 abstract description 14
• 229940002612 prodrug Drugs 0.000 abstract description 13
• 239000000651 prodrug Substances 0.000 abstract description 13
• 125000005750 substituted cyclic group Chemical group 0.000 abstract description 7
• 101150020251 NR13 gene Proteins 0.000 abstract description 4
• 229940075993 receptor modulator Drugs 0.000 abstract description 2
• 125000001183 hydrocarbyl group Chemical group 0.000 abstract 3
• -1 nitro, nitroso, phosphono Chemical group 0.000 description 475
• LPCQBTAOTIZGAE-UHFFFAOYSA-N 2h-pyrimidine-1-carboxamide Chemical compound NC(=O)N1CN=CC=C1 LPCQBTAOTIZGAE-UHFFFAOYSA-N 0.000 description 273
• 125000001424 substituent group Chemical group 0.000 description 183
• 125000000623 heterocyclic group Chemical group 0.000 description 152
• 150000002430 hydrocarbons Chemical group 0.000 description 151
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 110
• 125000003277 amino group Chemical group 0.000 description 107
• 125000003118 aryl group Chemical group 0.000 description 83
• 125000000217 alkyl group Chemical group 0.000 description 79
• 238000006243 chemical reaction Methods 0.000 description 74
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 74
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 72
• 235000002639 sodium chloride Nutrition 0.000 description 70
• 229910052757 nitrogen Inorganic materials 0.000 description 67
• 239000002904 solvent Substances 0.000 description 63
• 125000005843 halogen group Chemical group 0.000 description 56
• 125000003396 thiol group Chemical group [H]S* 0.000 description 56
• 229920006395 saturated elastomer Polymers 0.000 description 55
• 229910052717 sulfur Inorganic materials 0.000 description 53
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 52
• 125000004434 sulfur atom Chemical group 0.000 description 51
• 239000011575 calcium Substances 0.000 description 50
• 125000004433 nitrogen atom Chemical group N* 0.000 description 50
• 125000004430 oxygen atom Chemical group O* 0.000 description 50
• 125000005842 heteroatom Chemical group 0.000 description 47
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 46
• 125000004093 cyano group Chemical group *C#N 0.000 description 46
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 44
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 42
• 125000001931 aliphatic group Chemical group 0.000 description 41
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 40
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
• 238000000034 method Methods 0.000 description 38
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 37
• 239000002253 acid Substances 0.000 description 37
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 37
• 150000002367 halogens Chemical class 0.000 description 36
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 34
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 34
• 125000002252 acyl group Chemical group 0.000 description 34
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 33
• 125000003710 aryl alkyl group Chemical group 0.000 description 33
• 229910052736 halogen Inorganic materials 0.000 description 33
• 102000005962 receptors Human genes 0.000 description 33
• 108020003175 receptors Proteins 0.000 description 33
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
• 125000002723 alicyclic group Chemical group 0.000 description 32
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 31
• 125000002619 bicyclic group Chemical group 0.000 description 30
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 30
• 125000000041 C6-C10 aryl group Chemical group 0.000 description 29
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• 239000002585 base Substances 0.000 description 27
• 125000005115 alkyl carbamoyl group Chemical group 0.000 description 26
• 239000000203 mixture Substances 0.000 description 25
• 229940079593 drug Drugs 0.000 description 24
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 23
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
• 125000003545 alkoxy group Chemical group 0.000 description 22
• 231100000989 no adverse effect Toxicity 0.000 description 22
• 125000003386 piperidinyl group Chemical group 0.000 description 22
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 22
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 21
• 125000004414 alkyl thio group Chemical group 0.000 description 21
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 21
• 239000000460 chlorine Chemical group 0.000 description 21
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 21
• 229910052783 alkali metal Inorganic materials 0.000 description 20
• 229930195733 hydrocarbon Natural products 0.000 description 20
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 20
• 239000004215 Carbon black (E152) Substances 0.000 description 19
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 19
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 description 18
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
• 125000004070 6 membered heterocyclic group Chemical group 0.000 description 17
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 17
• JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 16
• 150000004945 aromatic hydrocarbons Chemical group 0.000 description 16
• 125000001624 naphthyl group Chemical group 0.000 description 16
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
• 238000002425 crystallisation Methods 0.000 description 15
• 230000008025 crystallization Effects 0.000 description 15
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
• 230000035484 reaction time Effects 0.000 description 15
• 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 description 14
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 14
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 14
• 238000004587 chromatography analysis Methods 0.000 description 14
• 238000004090 dissolution Methods 0.000 description 14
• 238000000605 extraction Methods 0.000 description 14
• 125000004043 oxo group Chemical group O=* 0.000 description 14
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 14
• 238000001953 recrystallisation Methods 0.000 description 14
• 230000002829 reductive effect Effects 0.000 description 14
• 238000012546 transfer Methods 0.000 description 14
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 13
• 125000004432 carbon atom Chemical group C* 0.000 description 13
• 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 13
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 12
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
• 150000001408 amides Chemical class 0.000 description 12
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 12
• 150000002170 ethers Chemical class 0.000 description 12
• 125000005946 imidazo[1,2-a]pyridyl group Chemical group 0.000 description 12
• 125000004076 pyridyl group Chemical group 0.000 description 12
• 239000000243 solution Substances 0.000 description 12
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 11
• LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 11
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 10
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 10
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 10
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 10
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 10
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 10
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
• CMDLMEWUTRWGGS-UHFFFAOYSA-N 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide Chemical compound C1CCNC2=C(C(=O)N)C=NN21 CMDLMEWUTRWGGS-UHFFFAOYSA-N 0.000 description 9
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 9
• 102000003982 Parathyroid hormone Human genes 0.000 description 9
• 108090000445 Parathyroid hormone Proteins 0.000 description 9
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 9
• 125000004104 aryloxy group Chemical group 0.000 description 9
• 125000000392 cycloalkenyl group Chemical group 0.000 description 9
• 230000032050 esterification Effects 0.000 description 9
• 238000005886 esterification reaction Methods 0.000 description 9
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 9
• 229910052739 hydrogen Inorganic materials 0.000 description 9
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 9
• 229910052751 metal Inorganic materials 0.000 description 9
• 239000002184 metal Substances 0.000 description 9
• 238000002156 mixing Methods 0.000 description 9
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
• 125000002347 octyl 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])[H] 0.000 description 9
• 239000000199 parathyroid hormone Substances 0.000 description 9
• 229960001319 parathyroid hormone Drugs 0.000 description 9
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 9
• 229910000027 potassium carbonate Inorganic materials 0.000 description 9
• 235000011181 potassium carbonates Nutrition 0.000 description 9
• 238000006722 reduction reaction Methods 0.000 description 9
• 150000003462 sulfoxides Chemical class 0.000 description 9
• 239000008096 xylene Substances 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 8
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
• 125000003282 alkyl amino group Chemical group 0.000 description 8
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
• 150000001412 amines Chemical class 0.000 description 8
• 239000003638 chemical reducing agent Substances 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• 238000007796 conventional method Methods 0.000 description 8
• 150000002148 esters Chemical class 0.000 description 8
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 8
• 125000002757 morpholinyl group Chemical group 0.000 description 8
• 125000003373 pyrazinyl group Chemical group 0.000 description 8
• 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
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