SK472004A3 - Purification and crystalline forms of zaleplon - Google Patents

Purification and crystalline forms of zaleplon Download PDF

Info

Publication number: SK472004A3
Authority: SK; Slovakia
Prior art keywords: zaleplon; solution; water; organic solvent; solvent
Prior art date: 2001-08-01

Application number

SK47-2004A

Other languages

English (en)

Slovak (sk)

Inventor

Erika Feher

Ferenc Korodi

Claude Singer

Erika Magyar

Original Assignee

Biogal Gyogyszergyar

Priority date (The priority date 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 date listed.)

2001-08-01

Filing date

2002-08-01

Publication date

2004-12-01

2002-06-12 Priority claimed from US10/170,673 external-priority patent/US6884888B2/en

2002-08-01 Application filed by Biogal Gyogyszergyar filed Critical Biogal Gyogyszergyar

2004-12-01 Publication of SK472004A3 publication Critical patent/SK472004A3/sk

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 abstract description 361
229960004010 zaleplon Drugs 0.000 title claims abstract description 287
238000000746 purification Methods 0.000 title abstract description 17
238000000034 method Methods 0.000 claims abstract description 93
230000008569 process Effects 0.000 claims abstract description 34
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 117
239000000243 solution Substances 0.000 claims description 111
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 93
239000000203 mixture Substances 0.000 claims description 68
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 68
239000003960 organic solvent Substances 0.000 claims description 66
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 59
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 59
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 52
239000012296 anti-solvent Substances 0.000 claims description 52
239000007787 solid Substances 0.000 claims description 46
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 40
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
238000001816 cooling Methods 0.000 claims description 39
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 39
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 31
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 30
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
238000002360 preparation method Methods 0.000 claims description 25
238000001556 precipitation Methods 0.000 claims description 21
239000007788 liquid Substances 0.000 claims description 20
239000008194 pharmaceutical composition Substances 0.000 claims description 20
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 20
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 17
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 16
239000002253 acid Substances 0.000 claims description 16
238000000634 powder X-ray diffraction Methods 0.000 claims description 16
238000004519 manufacturing process Methods 0.000 claims description 15
239000002244 precipitate Substances 0.000 claims description 15
239000002904 solvent Substances 0.000 claims description 14
-1 carboxyl nitriles Chemical class 0.000 claims description 13
239000000523 sample Substances 0.000 claims description 13
FFNKBQRKZRMYCL-UHFFFAOYSA-N 5-amino-1h-pyrazole-4-carbonitrile Chemical compound NC1=NNC=C1C#N FFNKBQRKZRMYCL-UHFFFAOYSA-N 0.000 claims description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 11
239000003480 eluent Substances 0.000 claims description 11
238000000926 separation method Methods 0.000 claims description 11
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
230000001376 precipitating effect Effects 0.000 claims description 9
239000000872 buffer Substances 0.000 claims description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 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
239000003085 diluting agent Substances 0.000 claims description 7
206010022437 insomnia Diseases 0.000 claims description 7
239000011541 reaction mixture Substances 0.000 claims description 7
239000000725 suspension Substances 0.000 claims description 7
238000012360 testing method Methods 0.000 claims description 7
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 6
238000009835 boiling Methods 0.000 claims description 6
239000012043 crude product Substances 0.000 claims description 6
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
150000001338 aliphatic hydrocarbons Chemical group 0.000 claims description 5
238000002425 crystallisation Methods 0.000 claims description 5
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238000010438 heat treatment Methods 0.000 claims description 5
239000012488 sample solution Substances 0.000 claims description 5
238000010828 elution Methods 0.000 claims description 4
229930195733 hydrocarbon Natural products 0.000 claims description 4
150000002430 hydrocarbons Chemical class 0.000 claims description 4
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238000002844 melting Methods 0.000 claims description 4
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239000012429 reaction media Substances 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
150000001298 alcohols Chemical class 0.000 claims description 3
150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 3
150000001733 carboxylic acid esters Chemical class 0.000 claims description 3
125000002843 carboxylic acid group Chemical group 0.000 claims description 3
238000004090 dissolution Methods 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
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 3
230000003472 neutralizing effect Effects 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
238000010898 silica gel chromatography Methods 0.000 claims description 3
239000004215 Carbon black (E152) Substances 0.000 claims description 2
238000007710 freezing Methods 0.000 claims description 2
230000008014 freezing Effects 0.000 claims description 2
238000002347 injection Methods 0.000 claims 2
239000007924 injection Substances 0.000 claims 2
206010053567 Coagulopathies Diseases 0.000 claims 1
150000007513 acids Chemical class 0.000 claims 1
230000003255 anti-acne Effects 0.000 claims 1
239000000010 aprotic solvent Substances 0.000 claims 1
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238000010583 slow cooling Methods 0.000 claims 1
239000006227 byproduct Substances 0.000 abstract description 7
239000013078 crystal Substances 0.000 abstract description 6
238000003786 synthesis reaction Methods 0.000 abstract description 5
235000019441 ethanol Nutrition 0.000 description 27
239000012535 impurity Substances 0.000 description 27
238000010992 reflux Methods 0.000 description 18
229960000583 acetic acid Drugs 0.000 description 14
238000001914 filtration Methods 0.000 description 12
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239000000047 product Substances 0.000 description 9
238000003756 stirring Methods 0.000 description 9
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
238000002441 X-ray diffraction Methods 0.000 description 8
239000004480 active ingredient Substances 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 8
239000003814 drug Substances 0.000 description 8
PMDCZENCAXMSOU-UHFFFAOYSA-N N-ethylacetamide Chemical compound CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 description 7
229940079593 drug Drugs 0.000 description 7
239000007790 solid phase Substances 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
239000001913 cellulose Substances 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
229920002907 Guar gum Polymers 0.000 description 5
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
239000000665 guar gum Substances 0.000 description 5
235000010417 guar gum Nutrition 0.000 description 5
229960002154 guar gum Drugs 0.000 description 5
239000005457 ice water Substances 0.000 description 5
238000002955 isolation Methods 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
239000008107 starch Substances 0.000 description 5
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OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-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
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 4
239000011575 calcium Substances 0.000 description 4
229910052791 calcium Inorganic materials 0.000 description 4
229940125898 compound 5 Drugs 0.000 description 4
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 4
229940088679 drug related substance Drugs 0.000 description 4
229940061368 sonata Drugs 0.000 description 4
238000004611 spectroscopical analysis Methods 0.000 description 4
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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
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
235000010643 Leucaena leucocephala Nutrition 0.000 description 3
229920000881 Modified starch Polymers 0.000 description 3
238000005481 NMR spectroscopy Methods 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 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
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 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
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235000002906 tartaric acid Nutrition 0.000 description 1
238000010998 test method Methods 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
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
239000003021 water soluble solvent Substances 0.000 description 1
238000002424 x-ray crystallography Methods 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)
Inorganic Compounds Of Heavy Metals (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

SK47-2004A 2001-08-01 2002-08-01 Purification and crystalline forms of zaleplon SK472004A3 (en)

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 (en)	2001-08-01	2002-08-01	Purification and crystalline forms of zaleplon

Publications (1)

Publication Number	Publication Date
SK472004A3 true SK472004A3 (en)	2004-12-01

Family

ID=27496922

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK47-2004A SK472004A3 (en)	2001-08-01	2002-08-01	Purification and crystalline forms of zaleplon

Country Status (14)

Country	Link
US (2)	US6852858B2 (cs)
EP (1)	EP1430054A4 (cs)
JP (1)	JP2005523874A (cs)
CA (1)	CA2453751A1 (cs)
CZ (1)	CZ200471A3 (cs)
HR (1)	HRP20040180A2 (cs)
HU (1)	HUP0402253A3 (cs)
IL (1)	IL160076A0 (cs)
IS (1)	IS7128A (cs)
MX (1)	MXPA04001035A (cs)
NO (1)	NO20040887L (cs)
PL (1)	PL374176A1 (cs)
SK (1)	SK472004A3 (cs)
WO (1)	WO2003011228A2 (cs)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SG125971A1 (en) *	2000-08-03	2006-10-30	Wyeth Corp	Variable water hydrates of zaleplon and method forthe preparation thereof
CA2450384A1 (en) *	2001-06-12	2002-12-19	Biogal Gyogyszergyar Rt.	Process for the production of zaleplon
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
PL374176A1 (en) *	2001-08-01	2005-10-03	Biogal Gyogyszergyar Rt	Process for purifying n-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-n-ethylacetamide(zaleplon) and crystalline forms of zaleplon accessible with the process
AU2003218058A1 (en) *	2002-02-15	2003-09-04	Teva Gyogyszergyar Reszvenytarsasag	Powder composition comprising zaleplon of defined particle size distribution and pharmaceutical products made therefrom
CZ293015B6 (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)
KR101248123B1 (ko)	2003-09-04	2013-03-27	씨아이피엘에이 엘티디.	잘레플론의 합성
WO2005070931A1 (en) *	2004-01-14	2005-08-04	Mallinckrodt Inc.	Two-phase method for the synthesis of selected pyrazolopyrimidines
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
WO2006062129A1 (ja) *	2004-12-08	2006-06-15	Kuraray Co., Ltd.	（５α，７α）－３－スピロ－２’－（１’，３’－ジオキソラン）－２４－オキソコレスト－２２－エン－７－イルベンゾアートの製造方法
WO2007043939A1 (en) *	2005-10-07	2007-04-19	Astrazeneca Ab	Novel crystalline form of 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
RU2021125455A (ru)	2013-11-15	2021-10-05	Экебиа Терапьютикс, Инк.	Твердые формы { [5-(3-хлорфенил)-3-гидроксипиридин-2-карбонил]амино} уксусной кислоты, их композиции и применения

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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
EP1272181A2 (en)	2000-04-13	2003-01-08	Synthon B.V.	Modified release formulations containing a hypnotic agent
SG125971A1 (en) *	2000-08-03	2006-10-30	Wyeth Corp	Variable water hydrates of zaleplon and method forthe 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
CA2450384A1 (en) *	2001-06-12	2002-12-19	Biogal Gyogyszergyar Rt.	Process for the production of zaleplon
PL374176A1 (en) *	2001-08-01	2005-10-03	Biogal Gyogyszergyar Rt	Process for purifying n-[3-(3-cyanopyrazolo[1,5-a]pyrimidin-7-yl)phenyl]-n-ethylacetamide(zaleplon) and crystalline forms of zaleplon accessible with the process
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
CZ293015B6 (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 PL PL02374176A patent/PL374176A1/xx unknown
- 2002-08-01 US US10/211,461 patent/US6852858B2/en not_active Expired - Fee Related
- 2002-08-01 EP EP02765928A patent/EP1430054A4/en not_active Withdrawn
- 2002-08-01 HU HU0402253A patent/HUP0402253A3/hu unknown
- 2002-08-01 CZ CZ200471A patent/CZ200471A3/cs unknown
- 2002-08-01 JP JP2003516460A patent/JP2005523874A/ja active Pending
- 2002-08-01 SK SK47-2004A patent/SK472004A3/sk unknown
- 2002-08-01 WO PCT/US2002/024553 patent/WO2003011228A2/en not_active Ceased
- 2002-08-01 HR HR20040180A patent/HRP20040180A2/hr not_active Application Discontinuation
- 2002-08-01 IL IL16007602A patent/IL160076A0/xx unknown
- 2002-08-01 CA CA002453751A patent/CA2453751A1/en not_active Abandoned
- 2002-08-01 MX MXPA04001035A patent/MXPA04001035A/es unknown
2004
- 2004-01-28 IS IS7128A patent/IS7128A/is unknown
- 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
HUP0402253A2 (hu)	2005-02-28
US7348429B2 (en)	2008-03-25
EP1430054A4 (en)	2005-06-22
IL160076A0 (en)	2004-06-20
MXPA04001035A (es)	2004-06-22
CZ200471A3 (cs)	2004-11-10
WO2003011228A2 (en)	2003-02-13
IS7128A (is)	2004-01-28
EP1430054A2 (en)	2004-06-23
NO20040887L (no)	2004-02-27
HUP0402253A3 (en)	2005-12-28
CA2453751A1 (en)	2003-02-13
US20030130291A1 (en)	2003-07-10
PL374176A1 (en)	2005-10-03
US20050065168A1 (en)	2005-03-24
US6852858B2 (en)	2005-02-08
WO2003011228A3 (en)	2003-10-30
HRP20040180A2 (en)	2004-12-31
JP2005523874A (ja)	2005-08-11

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2012-12-03	FB9A	Suspension of patent application procedure