Boon, W. R. published the artcilePteridines. IV. Derivatives of 2,4-diaminopteridine and related compounds, Formula: C6H9N3O2, the publication is Journal of the Chemical Society (1957), 2146-58, database is CAplus.
cf. C.A. 46, 2082g. Several derivatives of 2,4-(H2N)2-Y (in this abstract Y = pteridine) possess antimalarial activity (Potter and Henshall, C.A. 51, 1974h). A series of 2,4,6,7-(H2N)2Ph2-Y were prepared in which the H2N groups were progressively substituted by Me. Antimalarial activity was immediately lost, but the compounds were active against exptl. schistosomiasis in mice. Further modifications of the substituents always lowered the activity. Only a few compounds showed any appreciable activity. 2,4,6-Me2N-(HO)2-Z (in this abstract Z = pyrimidine) ground to pass a 30-mesh sieve, added with stirring during 45 min. to 280 cc. AcOH and 65 cc. HNO3 (d. 1.5) at 20-5°, stirred an addnl. 45 min., the mixture poured into 1350 cc. H2O, the solid separated, washed free from acid, and dried gave 81 g. 5-O2N derivative (I). I (5 g.), 60 cc. POCl3, and 20 cc. PhNMe2 heated to 105° (bath temperature), after the vigorous reaction the heating continued 1 hr., excess POCl3 removed in vacuo, the residue treated with 200 g. ice, the suspension extracted with four 50-cc. portions of Et2O, the combined extracts dried, filtered, evaporated, and the residue crystallized from petr. ether (b. 60-80°) gave 3.7 g. 4,6-Cl2 compound (II), m. 117-20°. II (14 g.), 90 cc. C6H6, and 10 cc. aqueous NH3 (d. 0.880) shaken overnight, the mixture filtered, and the residue (4.2 g.) crystallized twice from dioxane gave the 4,6-(H2N)2 compound, m. 249-50°; evaporation of the filtrate gave a residue which, after chromatography on 120 g. Al2O3 in 30 cc. C6H6 and crystallization from EtOAc-petr. ether afforded 0.5 g. 4-H2N compound, m. 132°. To 91 g. Na in 2 l. MeOH was added 509 g. [MeHNC(:NH)NH2]2.H2SO4, the mixture refluxed 30 min. with stirring, CH2(CO2Et)2 added, the heating continued 6 hrs., the mixture cooled, diluted with 5 l. H2O, treated with C, filtered, the filtrate acidified to litmus with AcOH, and the precipitate collected to give 183 g. 2,4,6-MeHN(HO)2-Z (III); the mother liquors deposited 15 g. presumably 2-amino-1,4,5,6-tetrahydro-1-methyl-4,6-dioxo-Z, m. above 360°. III (93g.) and 510 g. POCl3 refluxed 1 hr., the mixture filtered through sintered glass, the filtrate poured on 2250 cc. 32% aqueous NaOH and ice, the separated solid collected, washed with H2O, and crystallized from MeOH gave 88 g. 2,4,6-(MeHN)Cl2-Z (IV), m. 164°. IV (130 g.) heated 12 hrs. with NaOMe (from 168 g. Na in 570 cc. MeOH), the solution cooled, the precipitate collected, washed with H2O, and crystallized from MeOH yielded 95 g. 4,6,2-Cl(MeO)(MeHN)-Z, m. 153°. Similarly was prepared 81% 4,6,2-Cl(MeO)(Me2N)-Z (VI), m. 62° (after sublimation at 55°/0.1 mm.), from 4,6,2-Cl2(Me2N)-Z at room temperature VI (10 g.) heated 30 min. on a steam bath with 50 cc. HCl, the solution cooled, the product collected, and purified by solution in aqueous alkali, treatment with C, and reprecipitation with AcOH gave 5.5 g. 6-HO compound, m. 265° (decomposition). Similarly was obtained from VI 95% 4,6,2-Cl(HO)(Me2N)-Z (VII), m. 217°. 4,6,2-ClMe(H2N)-Z (28.7 g.) and 78 cc. 19.5% alc. Me2NH heated 17 hrs. at 110-20° gave 172 g. 4-Me2N derivative, m. 172° (from C6H6). Ph(H2N)CHCOPh.HCl (47 g.) dissolved in 750 cc. H2O. basified at 0° with aqueous NH3, the base collected, sucked as dry as possible, added to 35 g. 2,4,6-Cl3-Z (VIII) in 750 cc. EtOH, the mixture set aside 2 days at room temperature, the precipitate (12 g.) collected, and crystallized from EtOH gave α-(2,4-dichloro-6-pyrimidylamino)deoxybenzoin (IX), m. 165°. p-ClC6H4CHBzNH2 (X) (28.5 g.) converted to the base, the latter treated as above with 9 g. VIII, the crude product refluxed 3 hrs. with 10 cc. 19.5% alc. Me2NH and 10 cc. EtOH, the solution evaporated to 0.5 its volume, and the solid recrystallized from MeOH gave ω-(4-chloro-2-dimethylamino-6-pyrimidyl-amino)-ω-(p-chlorophenyl)acetophenone, m. 151-2°; the mother liquors gave the 6-Me2N isomer, m. 181-2° (from EtOH), and a small amount of another compound believed to be 2,5-di(p-chlorophenyl)-3,6-diphenylpyrazine, m. 239-40°. 4,6,2-Cl2(H2N)-Z (XI) (33 g.) heated 3 hrs. with 175 cc. 19.5% alc. Me2NH, after the initial reaction had subsided the solution cooled, the precipitate (24 g.) collected, and crystallized from MeOH and then from C6H6 gave 4,2,6-Cl(H2N)(Me2N)-Z, m. 164-5°. Similarly were obtained in 70% yield from the appropriate derivative of XI and an alc. solution of H2NCH2CO2Et, Et 4-chloro-2-methylamino-6-pyrimidylaminoacetate (XII), m. 167°, and Et 4-chloro-2-dimethylamino-6-pyrimidylamino-acetate, m. 121°. 2,4,6-Cl2(Me2N)-Z (36 g.), 200 cc. EtOH, and 50 cc. 70% aqueous EtNH2 refluxed 6 hrs., EtOH removed, the mixture diluted with H2O, extracted with Et2O, the extract dried, Et2O removed, the residue dissolved in 70 cc. absolute EtOH, 9 cc. concentrated H2SO4 added (the mixture acid to Congo red), and dry Et2O added to a permanent turbidity gave 34 g. 4,6,2-Cl(EtNH)(MeNH)-Z sulfate, m. 148° (from EtOH-Et2O). The following compounds were prepared similarly: 4,2,6-Cl(Me2N)(MeNH)-Z, m. 78° (from petr. ether); 4,2,6-Cl(Et2N)(MeNH)-Z sulfate, m. 148-9° (from EtOH-Et2O); 4-chloro-6-methylamino-2-piperidino-Z, m. 118° (from MeOH); 4,6,2-Cl(MeNH)(Me2NCH2CH2NH)-Z, m. 99° (from EtOAc-petr. ether). To 17.5 g. VII in 500 cc. H2O containing 60 cc. 2N NaOH and 12.6 g. NaHCO3 was added 4-ClC6H4N2Cl (XIII) [from 12.75 g. 4-ClC6H4NH2 (XIV)], the solution stirred overnight, the precipitate collected, washed with H2O, EtOH, and Et2O, and crystallized from dioxane to give 20 g. 5-p-ClC6H4N2 derivative (XV), m. 220-2° (decomposition). 4,6,2,5-Cl(HO)(MeNH)(p-ClC6H4N2)-Z was obtained similarly but could not be purified without decomposition XIII (500 cc. 0.025M) and 46 g. NaOAc.3H2O (XVI) added with stirring to 3.8 g. 6,4,2-Me(HO)(Me2N)-Z in 500 cc. H2O, after 16 hrs. the precipitate collected, washed, dried in air, and recrystallized from BuOH gave 5.5 g. 5-(p-ClC6H4N2) derivative, m. 216-17°. XIII (50 cc. 0.025M) and 40 g. XVI added with stirring to 5.0 g. 4,2,6-Cl(Me2N)2-Z in 70 cc. AcOH, diluted with 200 cc. H2O, after 48 hrs. stirring the solid collected, washed with H2O, and crystallized twice from EtOH gave 5 g. 5-(p-ClC6H4N2) derivative (XVII), m. 91°. The following N.CX:N.CW:C(N:NR).CY (XVIII) (W = Cl) were prepared (X, Y, R, m.p., crystallization solvent, % yield given): NH2, NHMe, p-ClC6H4, 255°, HCONMe (XIX), 47; NH2, NMe2, p-ClC6H4, 204°, XIX-EtOH, 65; NHMe, NH2, p-ClC6H4, 272° (decomposition), XIX, 90; NHMe, NHMe, p-ClC6H4, 272°, XIX-EtOH, 95; NHEt, NHMe, p-ClC6H4, 214°, BuOH, 75; NMe2, NH2, p-ClC6H4, 229°, BuOH, 90; NMe2, NHMe, Ph, 163°, EtOH, 78; NMe2, NHMe, p-ClC6H4, 183°, BuOH, 90; HNCH2CH2NMe2, NHMe, p-ClC6H4, 158°, EtOH, 50. 6,4,2,5-Cl(H2N)(Me2N)(p-ClC6 H4N2)-Z (XX) (2 g.) and 40 cc. saturated alc. NH3 heated 36 hrs. at 150-60°, the solution cooled, and the product (1.75 g.) crystallized from BuOH gave 6-H2N compound, m. 272-3° [HCl salt, m. 301° (decomposition) (from 80% HCO2H) (prepared from XIII and 4,6,2-(H2N)2(Me2N)-Z in AcOH)]. Similarly were prepared the following XVIII (W = NH2, R = p-ClC6H4) (X, Y, m.p., crystallization solvent, % yield given): NH2, NHMe, 213°, BuOH, 40 and 80; NH2, NMe2, 205°, XIX-H2O, 96; NH2,
Journal of the Chemical Society published new progress about 5738-14-7. 5738-14-7 belongs to pyrimidines, auxiliary class Pyrimidine,Amine,Alcohol,Pyrimidine, name is 2-(Dimethylamino)pyrimidine-4,6-diol, and the molecular formula is C6H9N3O2, Formula: C6H9N3O2.
Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia