NO153570B - Fremgangsmaate for fremstilling av 2-isopropylaminopyrimidin - Google Patents
Fremgangsmaate for fremstilling av 2-isopropylaminopyrimidin Download PDFInfo
- Publication number
- NO153570B NO153570B NO802372A NO802372A NO153570B NO 153570 B NO153570 B NO 153570B NO 802372 A NO802372 A NO 802372A NO 802372 A NO802372 A NO 802372A NO 153570 B NO153570 B NO 153570B
- Authority
- NO
- Norway
- Prior art keywords
- preparation
- mol
- pyrimidine
- bis
- sulfate
- Prior art date
Links
- FTCYIGBVOHNHCD-UHFFFAOYSA-N isaxonine Chemical compound CC(C)NC1=NC=CC=N1 FTCYIGBVOHNHCD-UHFFFAOYSA-N 0.000 title claims description 7
- 238000000034 method Methods 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 8
- MFIQZHWDRVKGAK-UHFFFAOYSA-N 2-propan-2-ylguanidine;sulfuric acid Chemical compound OS(O)(=O)=O.CC(C)NC(N)=N.CC(C)NC(N)=N MFIQZHWDRVKGAK-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- KVJHGPAAOUGYJX-UHFFFAOYSA-N 1,1,3,3-tetraethoxypropane Chemical compound CCOC(OCC)CC(OCC)OCC KVJHGPAAOUGYJX-UHFFFAOYSA-N 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 2
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- BZZXQZOBAUXLHZ-UHFFFAOYSA-N (c-methylsulfanylcarbonimidoyl)azanium;sulfate Chemical compound CSC(N)=N.CSC(N)=N.OS(O)(=O)=O BZZXQZOBAUXLHZ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 150000005006 2-aminopyrimidines Chemical class 0.000 description 1
- BWMDMTSNSXYYSP-UHFFFAOYSA-N 2-propylguanidine Chemical compound CCCNC(N)=N BWMDMTSNSXYYSP-UHFFFAOYSA-N 0.000 description 1
- BTMCCOMLYMKBFL-UHFFFAOYSA-N 2-propylpyrimidin-4-amine Chemical compound CCCC1=NC=CC(N)=N1 BTMCCOMLYMKBFL-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C277/08—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups of substituted guanidines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/48—Preparation of compounds having groups
- C07C41/50—Preparation of compounds having groups by reactions producing groups
- C07C41/54—Preparation of compounds having groups by reactions producing groups by addition of compounds to unsaturated carbon-to-carbon bonds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
Denne oppfinnelse angår en fremgangsmåte for fremstilling
av 2-isopropylamino-pyrimidin, en forbindelse som anvendes ved fremstilling av farmasøytiske forbindelser.
Fransk patent 886 084 beskriver fremstilling av 2-aminopyrimidin og ring-substituerte derivater derav. Det nevnes intet om fremstilling av derivater som er substituert på amino-gruppen i 2-stilling. Det høyeste utbytte som oppnås ifølge patentet, synes å være 75-80% ifølge patentets eksempel 12.
Fransk patent 957 802 angår fremstilling av substituert 2-aminopyrimidin, men utbyttene er i alle tilfeller dårlige,
idet det beste utbyttet synes å være 38% i eksempel 3. Fremstilling av 2-isopropylamino-pyrimidin er ikke beskrevet,
selv om propyl-guanidin er angitt som utgangsmateriale på
side 2, linje 95-96, øyensynlig for fremstilling av 2-propyl-amino-pyrimidin, uten at noe nærmere er angitt om fremstilling-
en .
Foreliggende fremgangsmåte er enkel å utføre og gir
meget gunstige utbytter.
Oppfinnelsen tilveiebringer en fremgangsmåte for fremstilling av 2-isopropylamino-pyrimidin, og den omfatter at 1 mol bis-(isopropylguanidin)-sulfat omsettes med 2 mol 1,1,3,3-tetra-etoksypropan ved tilbakeløpskjøling ved 40-60°C
i vandig saltsyreoppløsning, hvorefter 2-isopropylamino-
pyrimidin ekstraheres for reaksjonsblandingen med dietyleter.
1,1,3,3-tetraetoksy-propan kan fremstilles ved omsetning av et støkiometrisk overskudd av trietyl-ortoformiat med vinylacetat ved 70-90°C i nærvær av jern (III)klorid og eddiksyreanhydrid. Bis-(isopropylguanidin)-sulfat kan oppnås ved omsetning av et støkiometrisk overskudd av isopropylamin med bis-(S-metylisotiourinstoff)-sulfat under tilbake-løpskjøling.
Fremstilling av utgangsmaterialene.
(1) Fremstilling av 1, 1, 3, 3- tetraetoksy- propan
I en 1 liters reaktor utstyrt med oppvarmnings-, kjøle-
og røreutstyr ble hellet, under nitrogengjennomblåsning, 25,8 g (0,3 mol) vinylacetat og 125,8 g (0,85 mol) trietyl-ortoformiat. Blandingen ble oppvarmet til 70°C under omrøring. Derefter ble langsomt tilsatt (i løpet av 3 timer) 1,4 g jern(III)klorid og 2,2 g eddiksyreanhydrid. Efter tilsetningen ble omrøring fortsatt i 1/2 time og blandingen ble derefter avkjølt. Man fikk en sort blanding, og denne ble ekstrahert under anvendelse av 500 ml dietyleter. Efter vasking og tørring av ekstrakten ble dietyleteren fjernet under vakuum, slik at man fikk et olje-aktig produkt med kokepunkt 100-101°C ved 15 mm Hg.
Utbytte 56,8 g (86%).
(2) Fremstilling av bis-( isopropylguanidin)- sulfat
Inn i en 1 liters reaktor utstyrt med oppvarmnings-,
kjøle- og røreanordninger ble hellet 108,5 g (0,39 mol) bis-(S-metyl-isotiourinstoff)-sulfat, 150 ml vann og 94 ml (eller 68 g, dvs. 1,15 mol) isopropylamin. Blandingen ble tilbake-løpsbehandlet ved ca. 35°C i 2 timer og derefter inndampet til tørrhet. Residuet ble tatt opp i etanol fra hvilken det efter filtrering, vasking og tørring ble erholdt 96 g (utbytte 82%) produkt.
Eksempel
Fremstilling av 2- isopropylamino- pyrimidin
Inn i den samme reaktor som ble anvendt ved fremstillingen
av bis-(isopropylguanidin)-sulfat ble hellet 30 g (0,1 mol) bis-(isopropylguanidin)-sulfat, 120 ml vann, 75 ml ren salt-syreoppløsning (egenvekt 1,18) og langsomt (i løpet av 1 1/2
time), ved romtemperatur, 44 g (0,2 mol) 1,1,3,3-tetraetoksy-propan. Blandingen ble derefter oppvarmet til 50-55°C under omrøring i 2 timer, ble derefter avkjølt og nøytralisert ved hjelp av et overskudd av ren natriumhydroksydoppløsning. Blandingen ble ekstrahert under anvendelse av 300 ml dietyl-
eter. Ekstraktene ble vasket med en mettet oppløsning av natriumklorid, ble derefter tørret, og dietyleteren ble fjernet under vakuum. Man fikk 25 g (utbytte 91%) av en gulaktig olje med kokepunkt 91-91,5°C ved 11 mm Hg, og analysen viste god overensstemmelse med formelen C-^H-^N.^.
Claims (1)
- Fremgangsmåte for fremstilling av 2-isopropylamino-pyrimidin, karakterisert ved atl mol bis-(isopropylguanidin)-sulfat omsettes med 2 mol 1,1,3,3-tetraetoksy-propan ved tilbakeløpskjøling ved 40-60°C i vandig saltsyreoppløsning, hvorefter 2-isopropylamino-pyrimidin ekstraheres fra reaksjonsblandingen med dietyleter.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7927811 | 1979-08-09 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO802372L NO802372L (no) | 1981-02-10 |
| NO153570B true NO153570B (no) | 1986-01-06 |
| NO153570C NO153570C (no) | 1986-05-21 |
Family
ID=10507096
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO802372A NO153570C (no) | 1979-08-09 | 1980-08-08 | Fremgangsmaate for fremstilling av 2-isopropylaminopyrimidin. |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US4297495A (no) |
| JP (1) | JPS6054313B2 (no) |
| AR (1) | AR223383A1 (no) |
| AT (1) | AT375073B (no) |
| AU (1) | AU531561B2 (no) |
| BE (1) | BE883750A (no) |
| CA (1) | CA1132564A (no) |
| CH (1) | CH644110A5 (no) |
| DE (1) | DE3030171C2 (no) |
| DK (1) | DK341980A (no) |
| EG (1) | EG14476A (no) |
| ES (1) | ES493417A0 (no) |
| FI (1) | FI66355C (no) |
| FR (1) | FR2463130A1 (no) |
| GR (1) | GR67309B (no) |
| HK (1) | HK55783A (no) |
| IE (1) | IE50084B1 (no) |
| IL (1) | IL60235A (no) |
| IN (1) | IN154407B (no) |
| LU (1) | LU82518A1 (no) |
| MA (1) | MA18923A1 (no) |
| MX (1) | MX6740E (no) |
| MY (1) | MY8400205A (no) |
| NL (1) | NL8003617A (no) |
| NO (1) | NO153570C (no) |
| NZ (1) | NZ194018A (no) |
| OA (1) | OA06608A (no) |
| PT (1) | PT71657B (no) |
| SE (1) | SE435179B (no) |
| ZA (1) | ZA803339B (no) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4620006A (en) * | 1982-08-11 | 1986-10-28 | Eastman Kodak Company | Acid salts of 1-(cyanoalkyl)-4-guanylpiperazines |
| HU206337B (en) * | 1988-12-29 | 1992-10-28 | Mitsui Petrochemical Ind | Process for producing pyrimidine derivatives and pharmaceutical compositions |
| US5264435A (en) * | 1988-12-29 | 1993-11-23 | Mitsui Petrochemical Industries, Ltd. | Pyrimidines and their pharmaceutical acceptable salts, and their use as medicines |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA487444A (en) * | 1952-10-21 | William Copenhaver John | Process for producing pyrimidines | |
| FR886084A (fr) * | 1941-06-05 | 1943-10-04 | Schering Ag | Procédé de préparation de composés de la 2-amino-pyrimidine et de leurs dérivés ainsi que de composés se rattachant au propane et servant à leur fabrication |
-
1980
- 1980-06-04 IN IN413/DEL/80A patent/IN154407B/en unknown
- 1980-06-04 FI FI801796A patent/FI66355C/fi not_active IP Right Cessation
- 1980-06-04 ZA ZA00803339A patent/ZA803339B/xx unknown
- 1980-06-05 IL IL60235A patent/IL60235A/xx unknown
- 1980-06-06 GR GR62137A patent/GR67309B/el unknown
- 1980-06-10 BE BE0/200984A patent/BE883750A/fr not_active IP Right Cessation
- 1980-06-11 NZ NZ194018A patent/NZ194018A/xx unknown
- 1980-06-11 LU LU82518A patent/LU82518A1/fr unknown
- 1980-06-12 AT AT0311080A patent/AT375073B/de active
- 1980-06-23 NL NL8003617A patent/NL8003617A/nl not_active Application Discontinuation
- 1980-06-27 CH CH494580A patent/CH644110A5/fr not_active IP Right Cessation
- 1980-06-30 US US06/164,889 patent/US4297495A/en not_active Expired - Lifetime
- 1980-07-01 JP JP55088571A patent/JPS6054313B2/ja not_active Expired
- 1980-07-04 FR FR8014891A patent/FR2463130A1/fr active Granted
- 1980-07-10 SE SE8005078A patent/SE435179B/sv not_active IP Right Cessation
- 1980-07-11 AR AR281729A patent/AR223383A1/es active
- 1980-07-12 OA OA57165A patent/OA06608A/xx unknown
- 1980-07-16 ES ES493417A patent/ES493417A0/es active Granted
- 1980-07-18 CA CA356,532A patent/CA1132564A/en not_active Expired
- 1980-08-01 MA MA19123A patent/MA18923A1/fr unknown
- 1980-08-05 EG EG477/80A patent/EG14476A/xx active
- 1980-08-06 MX MX808960U patent/MX6740E/es unknown
- 1980-08-06 PT PT71657A patent/PT71657B/pt unknown
- 1980-08-07 IE IE1657/80A patent/IE50084B1/en unknown
- 1980-08-08 DE DE3030171A patent/DE3030171C2/de not_active Expired
- 1980-08-08 NO NO802372A patent/NO153570C/no unknown
- 1980-08-08 AU AU61192/80A patent/AU531561B2/en not_active Ceased
- 1980-08-08 DK DK341980A patent/DK341980A/da not_active Application Discontinuation
-
1983
- 1983-11-17 HK HK557/83A patent/HK55783A/xx unknown
-
1984
- 1984-12-30 MY MY205/84A patent/MY8400205A/xx unknown
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