NO802004L - Fremgangsmaate for fremstilling av 2-isopropylamino-pyrimidin - Google Patents
Fremgangsmaate for fremstilling av 2-isopropylamino-pyrimidinInfo
- Publication number
- NO802004L NO802004L NO802004A NO802004A NO802004L NO 802004 L NO802004 L NO 802004L NO 802004 A NO802004 A NO 802004A NO 802004 A NO802004 A NO 802004A NO 802004 L NO802004 L NO 802004L
- Authority
- NO
- Norway
- Prior art keywords
- pyrimidine
- isopropylamino
- preparing
- procedure
- yield
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 8
- FTCYIGBVOHNHCD-UHFFFAOYSA-N isaxonine Chemical compound CC(C)NC1=NC=CC=N1 FTCYIGBVOHNHCD-UHFFFAOYSA-N 0.000 title claims description 7
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- OIGXNHYFKZCTCH-UHFFFAOYSA-N 2-methylsulfonylpyrimidine Chemical compound CS(=O)(=O)C1=NC=CC=N1 OIGXNHYFKZCTCH-UHFFFAOYSA-N 0.000 claims description 5
- 238000007098 aminolysis reaction Methods 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 description 6
- FOEMIZSFFWGXHX-UHFFFAOYSA-N 2-methylsulfanylpyrimidine Chemical compound CSC1=NC=CC=N1 FOEMIZSFFWGXHX-UHFFFAOYSA-N 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- HBCQSNAFLVXVAY-UHFFFAOYSA-N pyrimidine-2-thiol Chemical compound SC1=NC=CC=N1 HBCQSNAFLVXVAY-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- KVJHGPAAOUGYJX-UHFFFAOYSA-N 1,1,3,3-tetraethoxypropane Chemical compound CCOC(OCC)CC(OCC)OCC KVJHGPAAOUGYJX-UHFFFAOYSA-N 0.000 description 1
- UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 1
- UZEKTDVGUQCDBI-UHFFFAOYSA-N 2-propan-2-ylguanidine Chemical compound CC(C)NC(N)=N UZEKTDVGUQCDBI-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 238000003408 phase transfer catalysis Methods 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000000725 suspension 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
- 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
- C07D239/38—One sulfur atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Flere synteser er foreslått for fremstilling av 2-isopropylamino-pyrimidin. Disse omfatter aminolyse av 2-klorpyrimidin med isopropylamin, og ringslutning av N-isopropylguanidin med 1,1,3,3-tetraetoksypropan.
I Europeisk patentansøkning 79400393.9 innlevert 15. juni 1979, beskrives syntese av 2-isopropylamino-pyrimidin ved inn-virkning av et alkaliborhydrid og en karboksylsyre på 2-amino-pyrimidin i nærvær av aceton.
Foreliggende oppfinnelse tilveiebringer en fremgangsmåte for fremstilling av 2-isopropylamino-pyrimidin ved aminolyse av 2-metylsulfonyl-pyrimidin under anvendelse av isopropylamin. Aminolysen foretas i henhold til foreliggende oppfinnelse ved tilbakeløpsbehandling av isopropylamin og 2-metylsulfonyl-pyrimidin i fravær av et oppløsningsmiddel. Under anvendelse av denne teknikk er 2-isopropylaminopyrimidin oppnådd i til-nærmet kvantitativt utbytte.
Syntesen av utgangsmaterialet, 2-metylsulfonyi-pyrimidin,
er beskrevet av Brown D. J.&Ford P.W. (J. Chem. Soc. (c) 1967 56 8) med 50% utbytte ved å starte fra 2-metyltio-pyrimidin.
Den metode som er beskrevet av Brown og Ford, omfatter bobling
av klor gjennom en vandig suspensjon av 2-metyltio-pyrimidin ved fra 0 til +5°C.
Denne metode er forbedret ved å føre klor langsommere gjennom suspensjonen og redusere reaksjonstemperaturen til fra -5 til 0°C. Det er således oppnådd et utbytte på ca. 90%.
Fremstillingen av 2-metyltio-pyrimidin ble først beskrevet av Boarland M.P.V. og McOmie J.P.W. (J. Chem. Soc. 1952, 3716) med et utbytte på 6 2%, ved å starte fra 2-merkapto-pyrimidin og metylsulfat. Hunig S. og Oette K.F. (Liebig's Annalen der Chemie, 1961, 640, 98) oppnådde et utbytte på 83%.
Faseoverføringskatalyse-teknikken ifølge Dou H. et al
(Phosphorus and Sulphur and the related elements, 1977, 3, 355)
ble anvendt for å oppnå 2-metyltio-pyrimidin i kvantitativt utbytte.
Det følgende reaksjonsskjema illustrerer syntesen ved
å starte fra 2-merkapto-pyrimidin.
Det følgende eksempel illustrerer forbedringen oppnådd ved hjelp av foreliggende fremgangsmåte.
Eksempel:
(a) Syntese av 2- metylsulfonyl- pyrimidin
Inn i en 200 ml reaktor ble innført 10 g (0,0794 mol) 2-metyltiopyrimidin og 100 ml vann.
Klor ble boblet langsomt gjennom ved en temperatur litt under 0°C. Efter 5 minutter fikk man en oppløsning. Gjennom-boblingen av klor ble fortsatt langsomt i 1 time mens den samme temperatur ble opprettholdt. I løpet av denne tid ble reaksjonens forløp overvåket ved tynnskiktkromatografi. Klortilførselen ble derefter avbrutt. Kolben ble ristet i ytterligere 1 time ved 0°C. pH-verdien ble regulert til 8 under anvendelse av ¥.^ C0^. Ekstraksjon ble foretatt med et klorert oppløsningsmiddel. Den organiske fase ble tørret under anvendelse av Na2S0^, og opp-løsningsmidlet ble derefter avdampet.
Man fikk et hvitt produkt som ble omkrystallisert to ganger fra etanol.
Utbytte 11,3 g: 90%. Sm.p. 70-72°C (litteratur 73-74°C).
(b) Syntese av 2- isopropylamino- pyrimidin
2 g (0,0126 mol) 2-metylsulfonyl-pyrimidin ble suspendert
i 20 ml isopropylamin.
Tilbakeløpsbehandling ble utført slik at man raskt fikk en oppløsning. Efter 1 time (reaksjonsforløpet ble kontrollert ved tynnskiktkromatografi) ble tilbakeløpsbehandlingen stanset, og overskudd av isopropylamin ble fjernet. Det ble tilsatt 100 ml vann, og pH ble regulert til 9 under anvendelse av soda-oppløsning.
Ekstraksjon ble foretatt med et klorert oppløsningsmiddel. Den organiske fase ble tørret over ^£30^, og oppløsningsmidlet ble avdampet.
Man fikk 1,7 g produkt (ca. 100% utbytte).
Produktet kunne anvendes som sådant eller i form av sine
Claims (1)
- Fremgangsmåte for fremstilling av 2-isopropylamino-pyrimidin ved aminolyse, karakterisert ved tilbakeløpsbehandling av støkiometriske mengder av isopropylamin og 2-metylsulfonyl-pyrimidin i fravær av et oppløsnings-middel.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7923224 | 1979-07-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO802004L true NO802004L (no) | 1981-01-05 |
Family
ID=10506281
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO802004A NO802004L (no) | 1979-07-04 | 1980-07-03 | Fremgangsmaate for fremstilling av 2-isopropylamino-pyrimidin |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US4266058A (no) |
| JP (1) | JPS6054312B2 (no) |
| AR (1) | AR222393A1 (no) |
| AT (1) | AT375072B (no) |
| AU (1) | AU529586B2 (no) |
| BE (1) | BE883751A (no) |
| CA (1) | CA1132563A (no) |
| CH (1) | CH644109A5 (no) |
| DE (1) | DE3025419C2 (no) |
| DK (1) | DK287480A (no) |
| EG (1) | EG14820A (no) |
| ES (1) | ES8105717A1 (no) |
| FI (1) | FI66356C (no) |
| FR (1) | FR2460937A1 (no) |
| GR (1) | GR69276B (no) |
| HK (1) | HK32584A (no) |
| IE (1) | IE49932B1 (no) |
| IL (1) | IL60234A (no) |
| IN (1) | IN154499B (no) |
| LU (1) | LU82517A1 (no) |
| MA (1) | MA18890A1 (no) |
| MX (1) | MX6162E (no) |
| NL (1) | NL8003616A (no) |
| NO (1) | NO802004L (no) |
| NZ (1) | NZ194017A (no) |
| OA (1) | OA06607A (no) |
| PT (1) | PT71477A (no) |
| SE (1) | SE435178B (no) |
| SG (1) | SG50383G (no) |
| ZA (1) | ZA803340B (no) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4661303A (en) * | 1985-06-11 | 1987-04-28 | The Dow Chemical Company | Reactive coextrusion of functionalized polymers |
| US5264435A (en) * | 1988-12-29 | 1993-11-23 | Mitsui Petrochemical Industries, Ltd. | Pyrimidines and their pharmaceutical acceptable salts, and their use as medicines |
| HU206337B (en) * | 1988-12-29 | 1992-10-28 | Mitsui Petrochemical Ind | Process for producing pyrimidine derivatives and pharmaceutical compositions |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2586844A (en) * | 1947-10-21 | 1952-02-26 | Ayerst Mckenna & Harrison | Preparation of delta2-1, 3-diazacycloalkenes |
| GB1523274A (en) * | 1974-08-05 | 1978-08-31 | Ici Ltd | Herbicidal compositions containing substituted pyrimidine |
-
1980
- 1980-06-04 IN IN414/DEL/80A patent/IN154499B/en unknown
- 1980-06-04 ZA ZA00803340A patent/ZA803340B/xx unknown
- 1980-06-05 FI FI801817A patent/FI66356C/fi not_active IP Right Cessation
- 1980-06-05 IL IL60234A patent/IL60234A/xx unknown
- 1980-06-06 GR GR62136A patent/GR69276B/el unknown
- 1980-06-10 BE BE0/200985A patent/BE883751A/fr not_active IP Right Cessation
- 1980-06-11 LU LU82517A patent/LU82517A1/fr unknown
- 1980-06-11 NZ NZ194017A patent/NZ194017A/xx unknown
- 1980-06-12 AT AT0310580A patent/AT375072B/de not_active IP Right Cessation
- 1980-06-23 US US06/162,114 patent/US4266058A/en not_active Expired - Lifetime
- 1980-06-23 NL NL8003616A patent/NL8003616A/nl not_active Application Discontinuation
- 1980-06-24 SE SE8004659A patent/SE435178B/sv not_active IP Right Cessation
- 1980-06-25 ES ES492747A patent/ES8105717A1/es not_active Expired
- 1980-06-27 CH CH494480A patent/CH644109A5/fr not_active IP Right Cessation
- 1980-06-30 JP JP55088001A patent/JPS6054312B2/ja not_active Expired
- 1980-06-30 IE IE1355/80A patent/IE49932B1/en unknown
- 1980-07-01 MA MA19087A patent/MA18890A1/fr unknown
- 1980-07-01 PT PT71477A patent/PT71477A/pt unknown
- 1980-07-01 MX MX808898U patent/MX6162E/es unknown
- 1980-07-02 AR AR281619D patent/AR222393A1/es active
- 1980-07-03 DK DK287480A patent/DK287480A/da unknown
- 1980-07-03 NO NO802004A patent/NO802004L/no unknown
- 1980-07-03 CA CA355,324A patent/CA1132563A/en not_active Expired
- 1980-07-04 AU AU60113/80A patent/AU529586B2/en not_active Ceased
- 1980-07-04 DE DE3025419A patent/DE3025419C2/de not_active Expired
- 1980-07-04 FR FR8014890A patent/FR2460937A1/fr active Granted
- 1980-07-04 OA OA57154A patent/OA06607A/xx unknown
- 1980-07-05 EG EG398/80A patent/EG14820A/xx active
-
1983
- 1983-08-13 SG SG50383A patent/SG50383G/en unknown
-
1984
- 1984-04-12 HK HK325/84A patent/HK32584A/xx unknown
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