HRP20040180A2 - Purification and crystalline forms of zaleplon - Google Patents
Purification and crystalline forms of zaleplonInfo
- Publication number
- HRP20040180A2 HRP20040180A2 HR20040180A HRP20040180A HRP20040180A2 HR P20040180 A2 HRP20040180 A2 HR P20040180A2 HR 20040180 A HR20040180 A HR 20040180A HR P20040180 A HRP20040180 A HR P20040180A HR P20040180 A2 HRP20040180 A2 HR P20040180A2
- Authority
- HR
- Croatia
- Prior art keywords
- zaleplon
- solution
- water
- organic solvent
- solid
- Prior art date
Links
- HUNXMJYCHXQEGX-UHFFFAOYSA-N zaleplon Chemical compound CCN(C(C)=O)C1=CC=CC(C=2N3N=CC(=C3N=CC=2)C#N)=C1 HUNXMJYCHXQEGX-UHFFFAOYSA-N 0.000 title claims description 359
- 229960004010 zaleplon Drugs 0.000 title claims description 306
- 238000000746 purification Methods 0.000 title description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 114
- 239000000243 solution Substances 0.000 claims description 109
- 238000000034 method Methods 0.000 claims description 103
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 84
- 239000000203 mixture Substances 0.000 claims description 81
- 239000003960 organic solvent Substances 0.000 claims description 64
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 64
- 239000007787 solid Substances 0.000 claims description 53
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 52
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 50
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 49
- 239000012296 anti-solvent Substances 0.000 claims description 47
- 238000002360 preparation method Methods 0.000 claims description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 36
- 238000001816 cooling Methods 0.000 claims description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 33
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 32
- 239000012535 impurity Substances 0.000 claims description 30
- 239000000523 sample Substances 0.000 claims description 29
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 24
- 238000001556 precipitation Methods 0.000 claims description 22
- 239000007788 liquid Substances 0.000 claims description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 239000000843 powder Substances 0.000 claims description 18
- 238000002441 X-ray diffraction Methods 0.000 claims description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 16
- ZMUMYMWAIXXLIY-UHFFFAOYSA-N n-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-5-yl)phenyl]-n-ethylacetamide Chemical compound CCN(C(C)=O)C1=CC=CC(C2=NC3=C(C#N)C=NN3C=C2)=C1 ZMUMYMWAIXXLIY-UHFFFAOYSA-N 0.000 claims description 15
- 238000000926 separation method Methods 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 14
- FFNKBQRKZRMYCL-UHFFFAOYSA-N 5-amino-1h-pyrazole-4-carbonitrile Chemical compound NC1=NNC=C1C#N FFNKBQRKZRMYCL-UHFFFAOYSA-N 0.000 claims description 13
- 239000002244 precipitate Substances 0.000 claims description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 11
- 239000003480 eluent Substances 0.000 claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 10
- UXWJJVRASIHSQS-MDZDMXLPSA-N n-[3-[(e)-3-(dimethylamino)prop-2-enoyl]phenyl]-n-ethylacetamide Chemical compound CCN(C(C)=O)C1=CC=CC(C(=O)\C=C\N(C)C)=C1 UXWJJVRASIHSQS-MDZDMXLPSA-N 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 9
- 239000000872 buffer Substances 0.000 claims description 8
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 7
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims description 7
- 238000009835 boiling Methods 0.000 claims description 7
- 206010022437 insomnia Diseases 0.000 claims description 7
- 239000000725 suspension Substances 0.000 claims description 7
- PMDCZENCAXMSOU-UHFFFAOYSA-N N-ethylacetamide Chemical compound CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 claims description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
- 238000010828 elution Methods 0.000 claims description 6
- 238000002955 isolation Methods 0.000 claims description 6
- 239000011541 reaction mixture Substances 0.000 claims description 6
- 239000000741 silica gel Substances 0.000 claims description 6
- 229910002027 silica gel Inorganic materials 0.000 claims description 6
- 150000001338 aliphatic hydrocarbons Chemical group 0.000 claims description 5
- 239000012043 crude product Substances 0.000 claims description 5
- 238000002425 crystallisation Methods 0.000 claims description 5
- 230000008025 crystallization Effects 0.000 claims description 5
- 230000008021 deposition Effects 0.000 claims description 5
- 238000010790 dilution Methods 0.000 claims description 5
- 239000012895 dilution Substances 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 239000012488 sample solution Substances 0.000 claims description 5
- 150000001735 carboxylic acids Chemical class 0.000 claims description 4
- 238000004587 chromatography analysis Methods 0.000 claims description 4
- 229930195733 hydrocarbon Natural products 0.000 claims description 4
- 150000002430 hydrocarbons Chemical class 0.000 claims description 4
- 230000008018 melting Effects 0.000 claims description 4
- 238000002844 melting Methods 0.000 claims description 4
- 150000002894 organic compounds Chemical class 0.000 claims description 4
- 239000008096 xylene Substances 0.000 claims description 4
- 150000003738 xylenes Chemical class 0.000 claims description 4
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 claims description 3
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 3
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 claims description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 3
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 3
- 125000002843 carboxylic acid group Chemical group 0.000 claims description 3
- 150000002170 ethers Chemical class 0.000 claims description 3
- 150000008282 halocarbons Chemical class 0.000 claims description 3
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 claims description 3
- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 claims description 3
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- 150000002825 nitriles Chemical class 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 235000019260 propionic acid Nutrition 0.000 claims description 3
- 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 3
- 239000004215 Carbon black (E152) Substances 0.000 claims description 2
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 2
- 239000012429 reaction media Substances 0.000 claims description 2
- 238000010998 test method Methods 0.000 claims description 2
- 230000001737 promoting effect Effects 0.000 claims 2
- 230000003472 neutralizing effect Effects 0.000 claims 1
- 238000010583 slow cooling Methods 0.000 claims 1
- 239000006104 solid solution Substances 0.000 claims 1
- 230000008023 solidification Effects 0.000 claims 1
- 238000007711 solidification Methods 0.000 claims 1
- 235000019441 ethanol Nutrition 0.000 description 24
- 238000010992 reflux Methods 0.000 description 19
- 229960000583 acetic acid Drugs 0.000 description 14
- 238000001914 filtration Methods 0.000 description 13
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- 235000011054 acetic acid Nutrition 0.000 description 12
- 238000003756 stirring Methods 0.000 description 10
- 239000000546 pharmaceutical excipient Substances 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 8
- 239000002552 dosage form Substances 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 229940079593 drug Drugs 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000006227 byproduct Substances 0.000 description 6
- 230000001376 precipitating effect Effects 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 239000013078 crystal Substances 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000008107 starch Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 229920002125 Sokalan® Polymers 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 229940125898 compound 5 Drugs 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 229920000609 methyl cellulose Polymers 0.000 description 4
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- 239000003826 tablet Substances 0.000 description 4
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 229920002907 Guar gum Polymers 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
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- 229920000881 Modified starch Polymers 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 235000010413 sodium alginate Nutrition 0.000 description 3
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- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- YMJLEPMVGQBLHL-UHFFFAOYSA-N 1h-pyrazole-5-carbonitrile Chemical compound N#CC1=CC=NN1 YMJLEPMVGQBLHL-UHFFFAOYSA-N 0.000 description 2
- XPCTZQVDEJYUGT-UHFFFAOYSA-N 3-hydroxy-2-methyl-4-pyrone Chemical compound CC=1OC=CC(=O)C=1O XPCTZQVDEJYUGT-UHFFFAOYSA-N 0.000 description 2
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- 229940080313 sodium starch Drugs 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 239000007892 solid unit dosage form Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
- 229940057977 zinc stearate Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
- Y10T436/145555—Hetero-N
- Y10T436/147777—Plural nitrogen in the same ring [e.g., barbituates, creatinine, etc.]
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- Neurology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Anesthesiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Inorganic Compounds Of Heavy Metals (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30939101P | 2001-08-01 | 2001-08-01 | |
| US31790701P | 2001-09-06 | 2001-09-06 | |
| US38819902P | 2002-06-12 | 2002-06-12 | |
| US10/170,673 US6884888B2 (en) | 2001-06-12 | 2002-06-12 | Process for the production of N-[3-(3-cyanopyrazolo[1,5-a] pyrimidin-7-yl) phenyl]-N-ethylacetamide (zaleplon) |
| PCT/US2002/024553 WO2003011228A2 (fr) | 2001-08-01 | 2002-08-01 | Procede de purification de n-[3-(3-cyanopyrazolo[1,5-a]pyrimidine-7-yl)phenyl]-n-ethylacetamide(zaleplon) et des formes cristallines de zaleplon auxquelles ce procede donne acces |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20040180A2 true HRP20040180A2 (en) | 2004-12-31 |
Family
ID=27496922
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR20040180A HRP20040180A2 (en) | 2001-08-01 | 2004-02-23 | Purification and crystalline forms of zaleplon |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US6852858B2 (fr) |
| EP (1) | EP1430054A4 (fr) |
| JP (1) | JP2005523874A (fr) |
| CA (1) | CA2453751A1 (fr) |
| CZ (1) | CZ200471A3 (fr) |
| HR (1) | HRP20040180A2 (fr) |
| HU (1) | HUP0402253A3 (fr) |
| IL (1) | IL160076A0 (fr) |
| IS (1) | IS7128A (fr) |
| MX (1) | MXPA04001035A (fr) |
| NO (1) | NO20040887L (fr) |
| PL (1) | PL374176A1 (fr) |
| SK (1) | SK472004A3 (fr) |
| WO (1) | WO2003011228A2 (fr) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL365678A1 (en) * | 2000-08-03 | 2005-01-10 | Wyeth | Polymorphs of zaleplon and methods for the preparation thereof |
| HUP0402257A2 (hu) * | 2001-06-12 | 2005-02-28 | BIOGAL Gyógyszergyár Rt. | Eljárás az N-[3-(3-cianopirazolo[1,5-a]pirimidin-7-il)-fenil]-N-etil-acetamid (zaleplon) előállítására |
| US20050032818A1 (en) * | 2001-06-12 | 2005-02-10 | Entire Interest | N-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-5-yl)phenyl]-N-ethylacetamide and crystalline forms of zaleplon |
| CA2453751A1 (fr) * | 2001-08-01 | 2003-02-13 | Biogal Gyogyszergyar Rt. | Procede de purification de n-[3-(3-cyanopyrazolo[1,5-a]pyrimidine-7-yl)phenyl]-n-ethylacetamide(zaleplon) et des formes cristallines de zaleplon auxquelles ce procede donne acces |
| KR20040086375A (ko) * | 2002-02-15 | 2004-10-08 | 비오갈 기오기스제르갸르 알티. | 소정의 입도 분포를 갖는 잘레플론을 포함하는 분말조성물 및 이로부터 생성된 약학적 생성물 |
| CZ20023575A3 (cs) * | 2002-10-25 | 2004-01-14 | Léčiva, A.S. | Způsob výroby N-ethyl-N-[3-(3-methyl-pyrazolo[1,5-a]pyrimidin-7-yl)-fenyl]-acetamidu (zaleplonu) |
| WO2005023813A1 (fr) | 2003-09-04 | 2005-03-17 | Cipla Limited | Synthese du zaleplon |
| CN1906197A (zh) * | 2004-01-14 | 2007-01-31 | 马林克罗特公司 | 用于合成选择的吡唑并嘧啶的两相方法 |
| HUP0400325A3 (en) * | 2004-02-02 | 2005-11-28 | Richter Gedeon Vegyeszet | Pure n-[3-(-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-n-ethyl-acetamide, process for its preparation and intermediates |
| EP1837343A4 (fr) * | 2004-12-08 | 2009-07-29 | Kuraray Co | Procédé servant à produire du benzoate de (5 alpha, 7 alpha)-3-spiro-2'-(1',3'-dioxolan)-24-oxocholest-22-èn-7-yle |
| WO2007043939A1 (fr) * | 2005-10-07 | 2007-04-19 | Astrazeneca Ab | Nouvelle forme cristalline de 3,5-dibromo-n-[(2s)-2-(4-fluorophenyl)-4-(3-morpholin-4-ylazetidin-1-yl)butyl]-n-methylbenzamide, modification a |
| US7761955B1 (en) * | 2007-08-30 | 2010-07-27 | Hiltz Erik D | Dual port cleaning and extraction apparatus |
| US8171598B1 (en) | 2010-07-26 | 2012-05-08 | Erik Daniel Hiltz | Dual port cleaning and extraction apparatus |
| MX2021001169A (es) | 2013-11-15 | 2023-02-10 | Akebia Therapeutics Inc | Formas sólidas de ácido {[5-(3-clorofenil)-3-hidroxipiridin-2-carb onil]amino}acético, composiciones, y usos de las mismas. |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4626538A (en) | 1983-06-23 | 1986-12-02 | American Cyanamid Company | [7-(3-disubstituted amino)phenyl]pyrazolo[1,5-a]pyrimidines |
| US5714607A (en) | 1995-12-01 | 1998-02-03 | American Cyanamid Company | Process improvement in the synthesis of N- 3-(3-cyano-pyrazolo 1,5-a!pyrimidin-7-yl)phenyl!-N-ethylacetamide |
| US6485746B1 (en) * | 2000-08-25 | 2002-11-26 | Neurocrine Biosciences, Inc. | Controlled-release sedative-hypnotic compositions and methods related thereto |
| DE10004790B4 (de) | 2000-02-01 | 2004-09-09 | Lts Lohmann Therapie-Systeme Ag | Transdermales therapeutisches System zur Verabreichung von Zaleplon, Verfahren zu seiner Herstellung und seine Verwendung |
| WO2001078725A2 (fr) | 2000-04-13 | 2001-10-25 | Synthon B.V. | Formulations a liberation modifiee contenant un agent hypnotique |
| PL365678A1 (en) * | 2000-08-03 | 2005-01-10 | Wyeth | Polymorphs of zaleplon and methods for the preparation thereof |
| AR029780A1 (es) * | 2000-12-13 | 2003-07-16 | Gador Sa | Procedimiento mejorado para la obtencion de n-[3(3-ciano-pirazolo[1,5-a]pirimidin-7-il)fenil]-n-etil-acetamida |
| HUP0402257A2 (hu) * | 2001-06-12 | 2005-02-28 | BIOGAL Gyógyszergyár Rt. | Eljárás az N-[3-(3-cianopirazolo[1,5-a]pirimidin-7-il)-fenil]-N-etil-acetamid (zaleplon) előállítására |
| CA2453751A1 (fr) * | 2001-08-01 | 2003-02-13 | Biogal Gyogyszergyar Rt. | Procede de purification de n-[3-(3-cyanopyrazolo[1,5-a]pyrimidine-7-yl)phenyl]-n-ethylacetamide(zaleplon) et des formes cristallines de zaleplon auxquelles ce procede donne acces |
| US7034155B2 (en) * | 2002-02-14 | 2006-04-25 | Cilag Ag | Method for producing n-ethyl-n-[3-(3-cyanopyrazolo[1,5a]pyrimidine-7-yl)phenyl]acetamide |
| PL207322B1 (pl) | 2002-05-14 | 2010-11-30 | Adamed Społka Z Ograniczoną Odpowiedzialnością | Sposób wytwarzania zaleplonu |
| CZ20023575A3 (cs) * | 2002-10-25 | 2004-01-14 | Léčiva, A.S. | Způsob výroby N-ethyl-N-[3-(3-methyl-pyrazolo[1,5-a]pyrimidin-7-yl)-fenyl]-acetamidu (zaleplonu) |
-
2002
- 2002-08-01 CA CA002453751A patent/CA2453751A1/fr not_active Abandoned
- 2002-08-01 JP JP2003516460A patent/JP2005523874A/ja active Pending
- 2002-08-01 EP EP02765928A patent/EP1430054A4/fr not_active Withdrawn
- 2002-08-01 CZ CZ200471A patent/CZ200471A3/cs unknown
- 2002-08-01 WO PCT/US2002/024553 patent/WO2003011228A2/fr not_active Application Discontinuation
- 2002-08-01 PL PL02374176A patent/PL374176A1/xx unknown
- 2002-08-01 MX MXPA04001035A patent/MXPA04001035A/es unknown
- 2002-08-01 SK SK47-2004A patent/SK472004A3/sk unknown
- 2002-08-01 IL IL16007602A patent/IL160076A0/xx unknown
- 2002-08-01 US US10/211,461 patent/US6852858B2/en not_active Expired - Fee Related
- 2002-08-01 HU HU0402253A patent/HUP0402253A3/hu unknown
-
2004
- 2004-01-28 IS IS7128A patent/IS7128A/is unknown
- 2004-02-23 HR HR20040180A patent/HRP20040180A2/hr not_active Application Discontinuation
- 2004-02-27 NO NO20040887A patent/NO20040887L/no not_active Application Discontinuation
- 2004-09-27 US US10/952,151 patent/US7348429B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| PL374176A1 (en) | 2005-10-03 |
| IS7128A (is) | 2004-01-28 |
| CZ200471A3 (cs) | 2004-11-10 |
| NO20040887L (no) | 2004-02-27 |
| IL160076A0 (en) | 2004-06-20 |
| HUP0402253A2 (hu) | 2005-02-28 |
| EP1430054A4 (fr) | 2005-06-22 |
| US7348429B2 (en) | 2008-03-25 |
| SK472004A3 (en) | 2004-12-01 |
| WO2003011228A3 (fr) | 2003-10-30 |
| CA2453751A1 (fr) | 2003-02-13 |
| JP2005523874A (ja) | 2005-08-11 |
| US6852858B2 (en) | 2005-02-08 |
| EP1430054A2 (fr) | 2004-06-23 |
| US20050065168A1 (en) | 2005-03-24 |
| WO2003011228A2 (fr) | 2003-02-13 |
| HUP0402253A3 (en) | 2005-12-28 |
| MXPA04001035A (es) | 2004-06-22 |
| US20030130291A1 (en) | 2003-07-10 |
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