GB590706A - New pyrimidine compounds - Google Patents
New pyrimidine compoundsInfo
- Publication number
- GB590706A GB590706A GB2588944A GB2588944A GB590706A GB 590706 A GB590706 A GB 590706A GB 2588944 A GB2588944 A GB 2588944A GB 2588944 A GB2588944 A GB 2588944A GB 590706 A GB590706 A GB 590706A
- Authority
- GB
- United Kingdom
- Prior art keywords
- diethylaminoethylamino
- diethylamino
- group
- methylpyrimidine
- methyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired
Links
- 150000003230 pyrimidines Chemical class 0.000 title abstract 3
- -1 hydrocarbon radical Chemical class 0.000 abstract 10
- 229910052739 hydrogen Inorganic materials 0.000 abstract 6
- 239000001257 hydrogen Substances 0.000 abstract 6
- 239000004215 Carbon black (E152) Substances 0.000 abstract 5
- 238000006243 chemical reaction Methods 0.000 abstract 5
- XHXFXVLFKHQFAL-UHFFFAOYSA-N Phosphoryl chloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 abstract 4
- 125000005647 linker group Chemical group 0.000 abstract 4
- 150000004985 diamines Chemical class 0.000 abstract 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 abstract 3
- 239000007858 starting material Substances 0.000 abstract 3
- SYRKLPUYGHMXDN-UHFFFAOYSA-N 2-methylquinoline-5,8-dione Chemical compound O=C1C=CC(=O)C2=NC(C)=CC=C21 SYRKLPUYGHMXDN-UHFFFAOYSA-N 0.000 abstract 2
- 239000002253 acid Chemical class 0.000 abstract 2
- 125000002252 acyl group Chemical group 0.000 abstract 2
- 125000001931 aliphatic group Chemical group 0.000 abstract 2
- 125000005084 alkoxyalkylaminoalkyl group Chemical group 0.000 abstract 2
- 125000003277 amino group Chemical group 0.000 abstract 2
- 239000003153 chemical reaction reagent Substances 0.000 abstract 2
- 230000000875 corresponding Effects 0.000 abstract 2
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 abstract 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract 2
- 238000010438 heat treatment Methods 0.000 abstract 2
- 125000000623 heterocyclic group Chemical group 0.000 abstract 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 2
- 125000004435 hydrogen atoms Chemical group [H]* 0.000 abstract 2
- 230000003993 interaction Effects 0.000 abstract 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 abstract 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 abstract 2
- 150000003839 salts Chemical class 0.000 abstract 2
- 239000011780 sodium chloride Substances 0.000 abstract 2
- 125000001424 substituent group Chemical group 0.000 abstract 2
- PIICEJLVQHRZGT-UHFFFAOYSA-N 1,2-ethanediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 abstract 1
- LEJMOTVCCRDZNE-UHFFFAOYSA-N 1-amino-3-(diethylamino)propan-2-ol Chemical compound CCN(CC)CC(O)CN LEJMOTVCCRDZNE-UHFFFAOYSA-N 0.000 abstract 1
- CJNRGSHEMCMUOE-UHFFFAOYSA-N 2-piperidin-1-ylethanamine Chemical compound NCCN1CCCCC1 CJNRGSHEMCMUOE-UHFFFAOYSA-N 0.000 abstract 1
- WRXNJTBODVGDRY-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanamine Chemical compound NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 abstract 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N 289-95-2 Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 abstract 1
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-Chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 abstract 1
- TYMLOMAKGOJONV-UHFFFAOYSA-N 4-Nitroaniline Chemical compound NC1=CC=C([N+]([O-])=O)C=C1 TYMLOMAKGOJONV-UHFFFAOYSA-N 0.000 abstract 1
- LONHIKNRVFLWFP-UHFFFAOYSA-N 4-[2-(diethylamino)ethylsulfanyl]aniline Chemical compound CCN(CC)CCSC1=CC=C(N)C=C1 LONHIKNRVFLWFP-UHFFFAOYSA-N 0.000 abstract 1
- DBPKMSBWOKAKLA-UHFFFAOYSA-N 4-chloropyrimidine Chemical class ClC1=CC=NC=N1 DBPKMSBWOKAKLA-UHFFFAOYSA-N 0.000 abstract 1
- JPFCCCDVVRPQQF-UHFFFAOYSA-N 4-methylsulfanylpyrimidine Chemical class CSC1=CC=NC=N1 JPFCCCDVVRPQQF-UHFFFAOYSA-N 0.000 abstract 1
- UBLKHAWYJFEPDX-UHFFFAOYSA-N 6-bromonaphthalen-2-amine Chemical compound C1=C(Br)C=CC2=CC(N)=CC=C21 UBLKHAWYJFEPDX-UHFFFAOYSA-N 0.000 abstract 1
- QNANRGHPXMUJQC-UHFFFAOYSA-N 6-chloro-2-methyl-1H-pyrimidin-4-one Chemical compound CC1=NC(=O)C=C(Cl)N1 QNANRGHPXMUJQC-UHFFFAOYSA-N 0.000 abstract 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract 1
- JILXUIANNUALRZ-UHFFFAOYSA-N N',N'-diethylbutane-1,4-diamine Chemical compound CCN(CC)CCCCN JILXUIANNUALRZ-UHFFFAOYSA-N 0.000 abstract 1
- JYCCKJSLUHEIDU-UHFFFAOYSA-N N',N'-diethylpentane-1,5-diamine Chemical compound CCN(CC)CCCCCN JYCCKJSLUHEIDU-UHFFFAOYSA-N 0.000 abstract 1
- DILRJUIACXKSQE-UHFFFAOYSA-N N',N'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 abstract 1
- MIFWXJNZWLWCGL-UHFFFAOYSA-N N'-butylpropane-1,3-diamine Chemical compound CCCCNCCCN MIFWXJNZWLWCGL-UHFFFAOYSA-N 0.000 abstract 1
- KFIGICHILYTCJF-UHFFFAOYSA-N N'-methylethane-1,2-diamine Chemical compound CNCCN KFIGICHILYTCJF-UHFFFAOYSA-N 0.000 abstract 1
- BHAAPTBBJKJZER-UHFFFAOYSA-N P-Anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 abstract 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N Phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 abstract 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N Picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 abstract 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M acetate Chemical class CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 abstract 1
- 230000002378 acidificating Effects 0.000 abstract 1
- 150000007513 acids Chemical class 0.000 abstract 1
- 125000002723 alicyclic group Chemical group 0.000 abstract 1
- 229910052783 alkali metal Inorganic materials 0.000 abstract 1
- 150000001340 alkali metals Chemical class 0.000 abstract 1
- 125000003545 alkoxy group Chemical group 0.000 abstract 1
- 125000003282 alkyl amino group Chemical group 0.000 abstract 1
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 125000004414 alkyl thio group Chemical group 0.000 abstract 1
- 238000005804 alkylation reaction Methods 0.000 abstract 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 abstract 1
- 239000002246 antineoplastic agent Substances 0.000 abstract 1
- 125000004104 aryloxy group Chemical group 0.000 abstract 1
- 125000004429 atoms Chemical group 0.000 abstract 1
- 239000011230 binding agent Substances 0.000 abstract 1
- 125000004663 dialkyl amino group Chemical group 0.000 abstract 1
- 239000003085 diluting agent Substances 0.000 abstract 1
- 125000001033 ether group Chemical group 0.000 abstract 1
- 125000005843 halogen group Chemical group 0.000 abstract 1
- 150000002431 hydrogen Chemical group 0.000 abstract 1
- 238000006460 hydrolysis reaction Methods 0.000 abstract 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
- 125000005181 hydroxyalkylaminoalkyl group Chemical group 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 abstract 1
- 150000007522 mineralic acids Chemical class 0.000 abstract 1
- 230000004048 modification Effects 0.000 abstract 1
- 238000006011 modification reaction Methods 0.000 abstract 1
- 229910052757 nitrogen Inorganic materials 0.000 abstract 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract 1
- 150000007524 organic acids Chemical class 0.000 abstract 1
- 235000005985 organic acids Nutrition 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- 239000001301 oxygen Substances 0.000 abstract 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N oxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 abstract 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 1
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical group NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 abstract 1
- 239000002904 solvent Substances 0.000 abstract 1
- 125000000547 substituted alkyl group Chemical group 0.000 abstract 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
- 125000000101 thioether group Chemical group 0.000 abstract 1
- 150000003568 thioethers Chemical class 0.000 abstract 1
- 125000003396 thiol group Chemical group [H]S* 0.000 abstract 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Pyrimidine compounds, useful as chemotherapeutic agents and as intermediates therefor, of the general formula <FORM:0590706/IV/1> wherein X and X1 each represents hydrogen or a hydrocarbon radical, Y represents hydrogen or a hydrocarbon radical which may bear one or more non-acidic substituents, R11 represents hydrogen or an alkyl or substituted alkyl (e.g. alkoxyalkyl or dialkylaminoalkyl) group, A represents an aliphatic, alicyclic or aliphatic-carbocyclic linking group which may be substituted by hydrocarbon radicals or hydroxy, alkoxy or dialkylaminoalkyl groups, and, when wholly or partly an aliphatic chain, may be interrupted by oxygen, nitrogen or sulphur atoms, and NRR1 represents a strongly basic amino or substituted amino group such as alkylamino, dialkylamino or piperidino or other strongly basic nitrogen-containing heterocyclic group, are manufactured by the interaction of a diamine R11NH-A-NRR1 with an appropriate 6-aminopyrimidine derivative bearing the atoms or groups X and X1 in the 2- and 5-positions and in the 4-position a labile substituent, such as a halogen atom or a hydrocarbon radical attached by an ether or thioether linkage, e.g. an alkoxy, aryloxy or alkylmercapto group. The reaction may be effected by heating the reagents together, optionally in the presence of a solvent or diluent. One or other of the reagents may be employed in the form of a salt, e.g. hydrochloride, or acetate, and an acid-binding agent such as sodium hydroxide may be present. When R1 represents hydrogen, the diamine may be replaced by its acyl derivative R11NH-A-NR-Ac, where R represents hydrogen or a hydrocarbon radical and Ac an acyl group which is subsequently removed by hydrolysis. A further modification consists in introducing the basic 4-substituent in stages by reacting the pyrimidine starting material with an amino compound R11NH-A1-B where A1 represents the whole or part of the linking group A, and B represents a reactive group which is then converted directly or indirectly, by methods involving reaction with ammonia or an amino compound, into the group NRR1 or into a group A11-NRR1 such that A1 and A11 together constitute the linking group A. The terminal amino group, when unsubstituted, may be subsequently modified, e.g. by alkylation, conversion to a heterocyclic group such as piperidino or by reaction with a halogeno-amine Hal-A111-NRRR1 so as to extend the linking group A to A-NH-A111. The products form salts with inorganic and organic acids, e.g. hydrogen halides or sulphuric, phosphoric, acetic, lactic, tartaric, lower alkanesulphonic (e.g. p methanesulphonic), picric, 3 : 5-dinitrobenzoic methylene bis-2 : 3-hydroxynaphthoic and methylene bis-salicyclic acids. In examples, the following products are made from the appropriate diamines and 4-chloropyrimidines : 4-g -dimethyl- and -diethyl-aminopropylamino- and 4 - b - diethylaminoethylamino - 6 - amino -2 : 5-dimethylpyrimidine; 4 - d - diethylamino - a - methylbutylamino-, 4 - b - diethylaminoethylamino- and 4 - g - diethylaminopropylamino-6-amino - 2 - methylpyrimidine; 4 - b - diethylaminoethylamino- 4 g - diethyl- and -di-n-butyl - aminopropylamino-, 4 - g - piperidino-propylamino-, 4 - d - diethylamino - a - methylbutylamino- and 4 - g - (b 1 - diethylaminoethoxy) - propylamino - 6 - p - chloroanilino - 2 - methylpyrimidine; 4 - b - diethylaminoethylamino-, 4 - g - diethylaminopropylamino- and 4 - g - diethylamino - a - methylbutylamino - 6 - p - methoxyanilino - 2 - methylpyrimidine; 4 - b - diethylaminoethylamino - and 4 - g - dimethyl- and -dibutyl - aminopropylamino - 6 - p - nitroanilino - 2 - methylpyrimidine; 4 - b - diethylaminoethylamino-, 4 - g - diethyl-, -dimethyl- and -dibutyl-aminopropylamino- and 4 - a - diethylamino - a - methylbutylamino - 6 - (61 - bromo - 21 - naphthylamino) - 2 - methylpyrimidine; 4 - b - diethylaminoethylamino - 6 - p - methoxyanilino - 2 : 5 - dimethylpyrimidine; 4 - b - diethylaminoethylamino -, 4 - g - diethyl- and -dimethyl-aminopropylamino- and 4 - [d - diethylamino - a - methylbutylamino-6-p-chloroanilino-2 : 5-dimethylpyrimidine; 4-b -diethylaminoethylamino- and 4-g -dimethyl- and -diethyl - aminopropylamino - 6 - p - chloroanilino - 2 - methyl - 5 - ethylpyrimidine; 4-b -diethylaminoethylamino - and 4 - g - dimethylaminopropylamino - 6 - p - methoxyanilino - 2 - methyl - 5 - ethylpyrimidine; 4 - b - diethylaminoethylamino- and 4 - g - diethylaminopropylamino - 6 - amino - 5 - methylpyrimidine; 4 : 6 - bis - (d - diethylamino - a - methylbutylamino) - 2 - methylpyrimidine; 4 - b - diethylaminoethylamino - 6 - p - nitroanilino - 2 : 5 - dimethylpyrimidine; 4 - b - diethylaminoethylamino - 6 - p - chloroanilino - 2 - phenylpyrimidine; and 4 - g - diethylaminopropylamino - 6 - p - chloroanilino - 2 - methyl - 5 - phenylpyrimidine. Additional starting materials specified are, on the one hand, 4-bromo-, 4-ethoxy-, 4-phenoxy- and 4-methylmercaptopyrimidines, and on the other hand, ethylenediamine, 2 - dimethylaminoethylamine, 4 - diethylaminobutylamine, 3 - diethylamino - 1 : 2 - dimethylpropylamine, 3 - diethylamino - 2 - hydroxypropylamine, 2 - methylaminoethylamine, 3 - n - butylaminopropylamine, 3 - (b - diethylaminoethylmercapto) - propylamine, 5-diethylamino - 1 - aminopentane, 2 - pyrrolidinoethylamine, 1 : 3 - bis - diethylamino - 2 - aminopropane, N - ethyl - N b - diethylaminoethyl - ethylenediamine, 2 - piperidinoethylamine, p - dimethyl - and - diethyl - aminoethoxyaniline, p - diethylaminoethylmercaptoaniline, 3 - diethylamino - 2 : 2 - dimethylpropylamine, N - methyl - N - b - diethylaminoethyl - 1 : 3 - propylenediamine, b - piperidino - b - methylethylamine, N-methyl and N-ethyl-N1-diethyl-ethylenediamine and bis-(b -diethylaminoethyl)-amine. Specification 584,917 is referred to. 4 - Halogeno - 6 - aminopyrimidine derivatives of the kind employed as starting materials are obtained by interaction of an amino-compound Y-NH2, e.g. p-chloroaniline, p-anisidine, p-nitroaniline or 6-bromo-2-naphthylamine, with the appropriate 4 : 6-dihalogenopyrimidine, e.g. 2 - methyl -, 2 : 5 - dimethyl -, 2 - methyl - 5 - ethyl- or 2 - methyl - 5 - phenyl - 4 : 6 - dichloropyrimidine, which dihalogeno-compounds are obtained by the action of phosphorus oxychloride or oxybromide on the corresponding 4 : 6-dihydroxy-compounds. The corresponding pyrimidines containing ether or thioether groups in the 4-position are obtainable by reaction of the 4-halogeno-derivatives with the appropriate hydroxy or mercapto compounds or their alkali metal derivatives. 4 - Chloro - 6 - (g - diethylamino - a - methylbutylamino) - 2 - methylpyrimidine is obtainable is obtainable by heating 4-chloro-6-hydroxy-2-methylpyrimidine with d - diethylamino - a - methylbutylamine and phosphorus oxychloride,
Publications (1)
Publication Number | Publication Date |
---|---|
GB590706A true GB590706A (en) | 1947-07-25 |
Family
ID=1739610
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB2588944A Expired GB590706A (en) | 1945-02-27 | New pyrimidine compounds |
Country Status (1)
Country | Link |
---|---|
GB (1) | GB590706A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11077108B2 (en) * | 2016-09-07 | 2021-08-03 | The Regents Of The University Of California | Allosteric corticotropin-releasing factor receptor 1 (CRFR1) antagonists that decrease p-tau and improve cognition |
-
1945
- 1945-02-27 GB GB2588944A patent/GB590706A/en not_active Expired
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11077108B2 (en) * | 2016-09-07 | 2021-08-03 | The Regents Of The University Of California | Allosteric corticotropin-releasing factor receptor 1 (CRFR1) antagonists that decrease p-tau and improve cognition |
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