FI66356C - Foerfarande foer syntes av 2-isopropylamino-pyrimidin - Google Patents
Foerfarande foer syntes av 2-isopropylamino-pyrimidin Download PDFInfo
- Publication number
- FI66356C FI66356C FI801817A FI801817A FI66356C FI 66356 C FI66356 C FI 66356C FI 801817 A FI801817 A FI 801817A FI 801817 A FI801817 A FI 801817A FI 66356 C FI66356 C FI 66356C
- Authority
- FI
- Finland
- Prior art keywords
- pyrimidine
- isopropylamino
- syntes
- foerfarande foer
- synthesis
- Prior art date
Links
- FTCYIGBVOHNHCD-UHFFFAOYSA-N isaxonine Chemical compound CC(C)NC1=NC=CC=N1 FTCYIGBVOHNHCD-UHFFFAOYSA-N 0.000 title description 7
- 238000003786 synthesis reaction Methods 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- FOEMIZSFFWGXHX-UHFFFAOYSA-N 2-methylsulfanylpyrimidine Chemical compound CSC1=NC=CC=N1 FOEMIZSFFWGXHX-UHFFFAOYSA-N 0.000 description 4
- OIGXNHYFKZCTCH-UHFFFAOYSA-N 2-methylsulfonylpyrimidine Chemical compound CS(=O)(=O)C1=NC=CC=N1 OIGXNHYFKZCTCH-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 4
- 238000007098 aminolysis reaction Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 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
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- HBCQSNAFLVXVAY-UHFFFAOYSA-N pyrimidine-2-thiol Chemical compound SC1=NC=CC=N1 HBCQSNAFLVXVAY-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 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
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 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
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical compound NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 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
R5FH M fii)Kuu.LUTUS,UL*AISU // 7P / flgjA LJ 1 1 utlAggningssrript o 00 o o (M) /tatct3 c 07 D 239/M2 SUOMI-FINLAND «*) νμ^-μμι 8oi8i7 (P) -1111— ftr-tTnlnpitu 05.06.80 (23) AftapM—GNtfcMsdag 05.06.80 (41) TatecIrttlMtal_Mv*<*·«*( 05.01.81
Patent- och mltentywliw ' ’ Ami— «tejdod>inTXiä!!i^Jteo»r»a 29.06.8M
(3^3)(31) Pyi4«trn»oiteM--a^MprtortMt OM.07.79
Englanti-England(GB) 792322M
(71) Soci4t4 d'Etudes de Produits Chimiques, M, rue Thöodule Ribot, 75OI7 Paris, Ranska-Frankrike(FR) (72) Claude Demosthene, Aramon, Christian Aspisi, Boulbon, Ranska-Frankrike(FR) (7M) Leitzinger Oy (5M) 2-isopropyyliamino-pyrimidiinin synteesimenetelmä -Förfarande för syntes av 2-isopropylamino-pyrimidin 2-isopropyyliamino-pyrimidiinin valmistamiseksi on ehdotettu useita synteesejä. Niihin kuuluu 2-klooripyrimidiinin aminolyysi isopropyy-liamiinin kanssa ja N-isopropyyliguaniidin syklisointi 1,1,3,3-tetraetoksipropaanin kanssa.
Eurooppalaisessa patenttihakemuksessa 79400393.9, jätetty 15.6.1979, on kuvattu 2-isopropyyliamino-pyrimidiinin synteesi, jossa alkali-boorihydridin ja karboksyylihapon on annettu vaikuttaa 2-amino-pyrimidiiniin asetonin läsnäollessa.
Oheinen keksintö tuo esiin 2-isopropyyliamino-pyrimidiinin synteesi-menetelmän aminolyysillä. Keksinnön mukaisesti aminolyysi suoritetaan refluksoimalla stökiömetriset määrät isopropyyliamiinia ja 2-metyylisulfonyylipyrimidiiniä ilman liuotinta. Tätä tekniikkaa käyttämällä 2-isopropyyliamino-pyrimidiiniä on saatu oleellisesti kvantitaviitisella saannolla.
Brown D.J. ja Ford P.W. (J. Chem. Soc (c) 1967 568) on kuvannut lähtöaineen, 2-metyylisulfonyyli-pyrimidiinin synteesiä 50 % saannol- 2 66356 la lähtemällä 2-metyylitio-pvrimidiinistä. Brown'in ja Ford'in kuvaamassa tekniikassa kuplitetaan klooria 2-metvylitio-pvrimidiinin vesisuspension läpi O - +5°C:ssa.
Tätä tekniikkaahan parannettu johtamalla klooria hitaammin ja alentamalla reaktiolämpötila -5 - 0°C:een. Näin on saatu noin 90 % saanto.
Boarland M.P.V. ja McOmie J.P.W. (J. Chem. Soc. 1952/ 3716) ovat ensimmäiseksi kuvanneet 2-metvylitio-pvrimidiinin valmistamisen 62 % saannolla lähtemällä 2-merkapto-pyrimidiinistä ja metyvlisul-faatista. Hunig S. ja Oette K.F. (Liebig's Annalen der Chemie, 1961, 640, 98) saivat 83 % saannon.
Dou, H. et.al'in (Phosphorus and Sulphur and the related elements, 1977, 3, 355) faasinsiirto-katalvvttitökniikkaa on sovellettu 2-metyylitio-pyrimidiinin valmistamiseen kvantitatiivisella saannolla.
Seuraava reaktiokaavio havainnollistaa synteesiä lähtemällä 2-merkapto-pyrimidiinistä.
. N --N _ N _ N CH3 SH t ^)—SMe —i \C) 'y~ S02,1e—> (q ^)—nh-ch N CH3
Seuraava esimerkki havainnollistaa oheista menetelmän'parannusta Esimerkki: (a) 2-metyylisulfonyyli-pyrimidiinin synteesi 200 ml reaktoriin laitettiinlO g (0,0794 moolia) 2-metyvlitionvrimi-diiniä ja 100 ml vettä.
Klooria kuplitettiin hitaasti liuoksen läpi hieman alle 0°C:ssa.
5 minuutin kuluttua saatiin liuos. Kloorin hidasta johtamista jatkettiin 1 tunti pitämällä reaktioseos samassa lämpötilassa. Tänä aikana 3 66356 reaktion kulkua seurattiin ohutlevvkromatografiällä. Tämän jälkeen kloorin syöttö lopetettiin. Pulloa ravisteltiin vielä 1 tunti 0°C:ssa. pH säädettiin arvoon 8 kaliumkarbonaatilla. Uutto suoritettiin klooratulla liuottimena. Orgaaninen faasi kuivattiin natrium-sulfaatilla ja liuotin haihdutettiin pois.
Näin saatiin valkoista tuotetta, joka kiteytettiin kaksi kertaa uudelleen etanolista.
Saanto: 11,3 g: 90 %. Sp. 70 - 72°C (kirj. 73 - 74°C).
(b) 2-isopropyyllamlno-pyrlmidlinin synteesi 2 g (0,0126 moolia) 2-metyylisulfonyyli-pyrimidiiniä suspendoitiin 20 ml:aan isopropyyliamiinia.
Suspensiota refluksoitiin, jolloin saatiin nopeasti liuos. Tunnin kuluttua (reaktion kulkua seurattiin ohutlevvkromatografiällä) refluksointi lopetettiin ja ylimääräinen isopropyvliamiini pöistet-tiin. Lisättiin 100 ml vettä ja pH säädettiin arvoon 9 käyttämällä soodaliuosta.
Uutto suoritettiin klooratulla liuottimena. Orgaaninen faasi kuivattiin natriumsulfaatilla ja liuotin haihdutettiin pois.
Saatiin 1,7 g tuotetta (saanto noin lOO %).
Tuote voidaan käyttää sellaisenaan tai suoloinaan.
j
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7923224 | 1979-07-04 | ||
| GB7923224 | 1979-07-04 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI801817A7 FI801817A7 (fi) | 1981-01-05 |
| FI66356B FI66356B (fi) | 1984-06-29 |
| FI66356C true FI66356C (fi) | 1984-10-10 |
Family
ID=10506281
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI801817A FI66356C (fi) | 1979-07-04 | 1980-06-05 | Foerfarande foer syntes av 2-isopropylamino-pyrimidin |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US4266058A (fi) |
| JP (1) | JPS6054312B2 (fi) |
| AR (1) | AR222393A1 (fi) |
| AT (1) | AT375072B (fi) |
| AU (1) | AU529586B2 (fi) |
| BE (1) | BE883751A (fi) |
| CA (1) | CA1132563A (fi) |
| CH (1) | CH644109A5 (fi) |
| DE (1) | DE3025419C2 (fi) |
| DK (1) | DK287480A (fi) |
| EG (1) | EG14820A (fi) |
| ES (1) | ES8105717A1 (fi) |
| FI (1) | FI66356C (fi) |
| FR (1) | FR2460937A1 (fi) |
| GR (1) | GR69276B (fi) |
| HK (1) | HK32584A (fi) |
| IE (1) | IE49932B1 (fi) |
| IL (1) | IL60234A (fi) |
| IN (1) | IN154499B (fi) |
| LU (1) | LU82517A1 (fi) |
| MA (1) | MA18890A1 (fi) |
| MX (1) | MX6162E (fi) |
| NL (1) | NL8003616A (fi) |
| NO (1) | NO802004L (fi) |
| NZ (1) | NZ194017A (fi) |
| OA (1) | OA06607A (fi) |
| PT (1) | PT71477A (fi) |
| SE (1) | SE435178B (fi) |
| SG (1) | SG50383G (fi) |
| ZA (1) | ZA803340B (fi) |
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 ZA ZA00803340A patent/ZA803340B/xx unknown
- 1980-06-04 IN IN414/DEL/80A patent/IN154499B/en 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 NZ NZ194017A patent/NZ194017A/xx unknown
- 1980-06-11 LU LU82517A patent/LU82517A1/fr 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 MX MX808898U patent/MX6162E/es unknown
- 1980-07-01 PT PT71477A patent/PT71477A/pt unknown
- 1980-07-02 AR AR281619D patent/AR222393A1/es active
- 1980-07-03 NO NO802004A patent/NO802004L/no unknown
- 1980-07-03 DK DK287480A patent/DK287480A/da unknown
- 1980-07-03 CA CA355,324A patent/CA1132563A/en not_active Expired
- 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
- 1980-07-04 AU AU60113/80A patent/AU529586B2/en not_active Ceased
- 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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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: SOCIETE D'ETUDES DE PRODUITS CHIMIQUES |