2,4,6-Triaminopyrimidine

2,4,6-Triaminopyrimidin Struktur.svg Pyrimidine-2,4,6-triamine 1004-38-2 39857 571518 13263 213-720-7 405732 13863 D6ZP6F2ECK 1S/C4H7N5/c5-2-1-3(6)9-4(7)8-2/h1H,(H6,5,6,7,8,9) JTTIOYHBNXDJOD-UHFFFAOYSA-N C1=C(N=C(N=C1N)N)N C4H7N5 125,13 g·mol−1 2,4,6-Triaminopyrimidine is a pyrimidine (1,3-diazine) carrying three symmetrically arranged amino groups and has been proposed as a potential prebiotic nucleic base analog.Menor Salván C. Bouza Marcos Fialho David M. Burcar Bradley T. Fernández Facundo M. Hud Nicholas V. 2020 https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cbic.202000510 10.1002/cbic.202000510 24 3504–3510 ChemBioChem Prebiotic Origin of Pre-RNA Building Blocks in a Urea 'Warm Little Pond' Scenario 21 32770593 subscription Pyrimidine triamine serves as a starting material for the production of hair dyes and explosives, but most notably for the vitamin folic acid and for pharmaceuticals such as malaria treatments, the cytostatic agents aminopterin and methotrexate, as well as the diuretic triamterene. Occurrence and preparation In 1905, Wilhelm Traube reported the synthesis of 2,4,6-triaminopyrimidine from malonic acid dinitrile and guanidine in the presence of sodium methanolate using ethanol as solvent.W. Traube 1904 10.1002/cber.19040370454 4 4544–4547 Chem. Ber. Über (2)-Amino-Adenin (2.6-Diaminopurin) 37 400px|center|Synthesis of 2,4,6-triaminopyrimidine The product can be isolated from the solution as a well-crystallizing sulfate. When a more manageable guanidine salt is used, e.g. guanidine hydrochloride, the base sodium methanolate is added to liberate free guanidine.US 4145548 Method for the production of 5-nitroso-2,4,6-triaminopyrimidine 1979-3-20 1977-11-10 D. Rose Henkel KGaA Because the aromatic triamine is highly sensitive to oxidation, all operations must be carried out under exclusion of air. The synthesis of TAP using guanidine bound to polystyrene according to the principle of a Merrifield synthesis, with malodinitrile and subsequent cleavage using trifluoroacetic acid under microwave chemistry conditions, has also been reported to yield very high product quantities (92%) within short reaction times.E.P. Aparna, K.S. Devaky 2018 8 67–72 J. Chem. Pharm. Res. Microwave assisted solid phase synthesis of trisubstituted pyrimidines https://www.jocpr.com/articles/microwave-assisted-solid-phase-synthesis-of-trisubstituted-9695.html 10 Properties Pure 2,4,6-triaminopyrimidine is a white crystalline solid "which precipitates in long needles when recrystallized from hot, dilute alcohol". The substance rapidly forms dark brown oxidation products upon exposure to air. TAP is highly soluble in water (36.5 g/kg at 20 °C) and in methanol (22.7 g/kg at 20 °C), but less soluble in ethanol (4.5 g/kg at 20 °C).Datenblatt 2,4,6-Triaminopyrimidin, 97 % bei Fisher Scientific, retrieved 28 November 2022. (PDF). Applications The spontaneous reaction of 2,4,6-triaminopyrimidine with ribose under simulated conditions of chemical evolution forms a nucleoside TAP–ribose conjugate that associates with complementary cyanuric acid. This reaction serves as a model for the prebiotic formation of ribonucleic acid (pre-RNA).Chen Michael C. Cafferty Brian J. Mamajanov Irena Gállego Isaac Khanam Jaheda Krishnamurthy Ramanarayanan Hud Nicholas V. 2013 https://pubs.acs.org/doi/10.1021/ja410124v 10.1021/ja410124v 15 5640–5646 J. Amer. Chem. Soc. Spontaneous prebiotic formation of a β-ribofuranoside that self-assembles with a complementary heterocycle 136 subscription Kaur Sarabjeet Sharma Purshotam Wetmore Stacey D. 2019 https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cphc.201900237 10.1002/cphc.201900237 11 1425–1436 ChemPhysChem Can Cyanuric Acid and 2,4,6-Triaminopyrimidine Containing Ribonucleosides be Components of Prebiotic RNA? Insights from QM Calculations and MD Simulations 20 30997731 subscription 450px|center|Conjugate of 2,4,6-triaminopyrimidine and ribose Reaction of 2,4,6-triaminopyrimidine with the sodium salt of nitromalonaldehydeExterne Identifikatoren von bzw. Datenbank-Links zu Nitromalondialdehyde monohydrate (Name im Wikidata-Eintrag abweichend, dort: Sodium nitromalonaldehyde): CAS-Nr.: 34461-00-2, EG-Nr.: 636-459-4, ECHA-InfoCard: 100.164.255, PubChem: 2786779 (Wert fehlt im Wikidata-Eintrag), ChemSpider: 21169750 (Wert fehlt im Wikidata-Eintrag), Wikidata: Q72508036. (prepared from mucobromic acidPaul E. Fanta: 2,4,6-Triaminopyrimidin In: Organic Syntheses. 32, 1952, S. 95, doi:10.15227/orgsyn.032.0095; Coll. Vol. 4, 1963, S. 844 (PDF). and nitrous acid) yields a heteroaromatic compound (A), which is subsequently converted in two steps into an inhibitor of dihydrofolate reductase active against Pneumocystis carinii and Toxoplasma gondii.Gangjee Aleem Vasudevan Anil Queener Sherry F. Kisliuk Roy L. 1996 https://pubs.acs.org/doi/10.1021/jm950786p 10.1021/jm950786p 7 1438–1446 J. Med. Chem. 2,4-Diamino-5-deaza-6-substituted pyrido[2,3-d]pyrimidine antifolates as potent and selective nonclassical inhibitors of dihydrofolate reductases 39 8691474 Gangjee Aleem Adair Ona O. Pagley Michelle Queener Sherry F. 2008 10.1021/jm800694g 19 6195–6200 J. Med. Chem. N9-Substituted 2,4-Diaminoquinazolines: Synthesis and Biological Evaluation of Lipophilic Inhibitors of Pneumocystis carinii and Toxoplasma gondii Dihydrofolate Reductase 51 18771252 3885247 550px|center|DHFR inhibitor from TAP Treatment of 2,4,6-triaminopyrimidine with nitrous acid (HNO2) affords the 5-nitroso compound (I), which can be further reduced using ammonium sulfide (NH4)2S, sodium dithionite (Na2S2O4),US 4167633 Preparation of 2,4,5,6-tetraaminopyrimidine from 2,4,6-triaminopyrimidine 1979-9-11 1977-7-20 T.J. Morrow The United States of America as represented by the Department of Health, Education and Welfare zinc dust/hydrochloric acid,US 4247693 Process for the preparation of 2,4,5,6-tetraaminopyrimidine sulfate 1981-1-27 1979-9-28 P.F. O'Brien, J. Kazan, J.R. Andrade American Cyanamide Co. or more effectively by catalytic hydrogenation over palladium to yield 2,4,5,6-tetraaminopyrimidineWO 9721711 Process preparing 4-aminopteridine derivatives 1997-06-19 1996-12-11 M. Eyer, W. Pfleiderer, S. Taghavi-Moghadam Lonza AG in das u. a. als Entwickler für oxidative HaarfarbenExterne Identifikatoren von bzw. Datenbank-Links zu 2,4,5,6-Tetraaminopyrimidin Name im Wikidata-Eintrag abweichend, dort: 2,4,5,6-tetraaminopyrimidine): CAS-Nr.: 1004-74-6, EG-Nr.: 213-724-9, ECHA-InfoCard: 100.012.477 PubChem: 70487, ChemSpider: 63662, Wikidata: Q15726087. (II). 450px|center|Synthesis of 2,4,5,6-tetraaminopyrimidine from TAP 5-Nitroso-2,4,6-triaminopyrimidine (I) can also be obtained directly in a one-pot reaction from the starting materials used for TAP without intermediate isolation, providing very good yields. In an early synthetic route for the potassium-sparing diuretic triamterene, 5-nitroso-2,4,6-triaminopyrimidine (I) is cyclized with phenylacetonitrileUS 3081230 Diuretic and antihypertensive triaminoarylpteridines 1963-3-12 1960-9-8 J. Weinstock, V.D. Wiebelhaus Smith Kline & French Laboratories in the presence of sodium methanolate to yield the final product. 400px|center|Synthesis of triamterene from TAP (last step) The extensive work conducted between 1970 and 2000 on the synthesis of 2,4,5,6-tetraaminopyrimidine from 2,4,6-triaminopyrimidine was driven by the high demand for this tetramine as a precursor for triamterene and particularly for the vitamin folic acid and its antagonists used in cancer therapy, such as aminopterin and especially methotrexate. 350px|center|Folic acid and antagonists derived from TAP References Category:Pyrimidines Category:Amines