NZ571829A - Crystalline forms and processes for the preparation of phenyl-pyrazoles useful as modulators of the 5-HT2A serotonin receptor - Google Patents

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Publication number

NZ571829A

NZ571829A NZ571829A NZ57182907A NZ571829A NZ 571829 A NZ571829 A NZ 571829A NZ 571829 A NZ571829 A NZ 571829A NZ 57182907 A NZ57182907 A NZ 57182907A NZ 571829 A NZ571829 A NZ 571829A

Authority

NZ

New Zealand

Prior art keywords

compound

formula

reacting

alkyl

process according

Prior art date

2006-05-18

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• 238000000034 method Methods 0.000 title claims abstract description 140
• 230000008569 process Effects 0.000 title claims abstract description 67
• 238000002360 preparation method Methods 0.000 title description 44
• 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 title description 15
• 108010072564 5-HT2A Serotonin Receptor Proteins 0.000 title description 14
• 150000008048 phenylpyrazoles Chemical class 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 323
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 69
• 208000035475 disorder Diseases 0.000 claims abstract description 50
• 125000003118 aryl group Chemical group 0.000 claims abstract description 34
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 32
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 32
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 25
• 239000003814 drug Substances 0.000 claims abstract description 24
• 238000004519 manufacturing process Methods 0.000 claims abstract description 19
• 238000011282 treatment Methods 0.000 claims abstract description 14
• 206010002383 Angina Pectoris Diseases 0.000 claims abstract description 13
• 150000003839 salts Chemical class 0.000 claims description 118
• 239000002904 solvent Substances 0.000 claims description 79
• 125000000217 alkyl group Chemical group 0.000 claims description 52
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 38
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 38
• 125000003342 alkenyl group Chemical group 0.000 claims description 34
• 125000000304 alkynyl group Chemical group 0.000 claims description 34
• 208000028017 Psychotic disease Diseases 0.000 claims description 32
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 28
• 239000002253 acid Substances 0.000 claims description 27
• 150000001412 amines Chemical class 0.000 claims description 27
• 201000000980 schizophrenia Diseases 0.000 claims description 25
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 19
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical group Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 18
• 125000002252 acyl group Chemical group 0.000 claims description 17
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
• 230000035602 clotting Effects 0.000 claims description 16
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• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
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• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 9
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• PQLAYKMGZDUDLQ-UHFFFAOYSA-K aluminium bromide Chemical compound Br[Al](Br)Br PQLAYKMGZDUDLQ-UHFFFAOYSA-K 0.000 claims description 4
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• KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 claims description 4
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• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 4
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 3
• 229910002651 NO3 Inorganic materials 0.000 claims description 3
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 3
• 229910019142 PO4 Inorganic materials 0.000 claims description 3
• 150000001350 alkyl halides Chemical class 0.000 claims description 3
• 235000019253 formic acid Nutrition 0.000 claims description 3
• LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 3
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
• 239000010452 phosphate Substances 0.000 claims description 3
• 239000011592 zinc chloride Substances 0.000 claims description 3
• 235000005074 zinc chloride Nutrition 0.000 claims description 3
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 3
• 150000002825 nitriles Chemical class 0.000 claims description 2
• 125000004971 nitroalkyl group Chemical group 0.000 claims description 2
• MCSAJNNLRCFZED-UHFFFAOYSA-N nitroethane Chemical compound CC[N+]([O-])=O MCSAJNNLRCFZED-UHFFFAOYSA-N 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• QGJOPFRUJISHPQ-NJFSPNSNSA-N carbon disulfide-14c Chemical compound S=[14C]=S QGJOPFRUJISHPQ-NJFSPNSNSA-N 0.000 claims 2
• 229910010165 TiCu Inorganic materials 0.000 claims 1
• 150000001735 carboxylic acids Chemical class 0.000 claims 1
• 125000001475 halogen functional group Chemical group 0.000 claims 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 claims 1
• -1 pyrazole phenol compound Chemical class 0.000 abstract description 36
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 abstract 1
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• 238000006243 chemical reaction Methods 0.000 description 66
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