Spiteller, G.; Bretschneider, H. published the artcile< Preparation of 2,6-disubstituted 4-sulfanilamidopyrimidines>, Related Products of 3286-55-3, the main research area is .
Crude 2,6-dichloro-4-aminopyrimidine (I) (21.2 g.) was treated portionwise with 50 ml. NaOMe (3.14 g. Na) at 35°, the mixture heated 1 hr. at 50° with stirring, MeOH distilled in vacuo at 40°, and the residue treated with 30 ml. H2O yielded after filtration 14.2 g. 2-methoxy-4-amino-6-chloropyrimidine (II), m. 130° (H2O), sublimable at 120° (0.5 mm.). CaCO3Pd catalyst (1.3 g.) hydrogenated in 10 ml. absolute MeOH was added to 798 mg. II in 35 ml. absolute methanolic NaOH and the mixture hydrogenated to yield 510 mg. 2-methoxy-4-aminopyrimidine, m. 160-7°; mixed m.p. with authentic material gave no depression. II (13.4 g.) was treated with 20 ml. NaOMe (113 mg. Na/ml.) and 10 ml. 90% EtSH, the mixture heated 2 hrs. at 100° in an autoclave, cooled, MeOH and excess EtSH distilled in vacuo, the residue treated with 20 ml. H2O, the oil obtained dissolved in 150 ml. Et2O, washed with H2O, dried, evaporated, and petr. ether added to give 13.1 g. 2-methoxy-4-amino-6-ethylthiopyrimidine (III), m. 83-4°, b0.5 140°. I (24.6 g.) was treated with 20 ml. EtSH, 48 ml. absolute MeOH, and 3.75 g. Na, the mixture heated 1 hr. in an autoclave at 50°, MeOH and excess EtSH distilled in vacuo at 50°, the residue taken up in 20 ml. H2O and 200 ml. Et2O, washed with H2O, the Et2O solution dried, and 2-ethylthio-4-amino-6-chloropyrimidine (IV) precipitated with petr. ether, m. 78-79°, b0.5 130°. Crude IV (17.5 g.) was treated with 30 ml. NaOMe solution (containing 2.1 g. Na) in an autoclave 2 hrs. at 100°, the mixture evaporated, and the residue treated with H2O to give 2-ethylthio-4-amino-6-methoxy pyrimidine (V), m. 117-18° (Et2O), b0.5 135-40°. I (8.4 g.) treated in an autoclave with 20 ml. EtSH and 38 ml. NaOMe (2.8 g. Na) and heated 6 hrs. at 110° gave 2,6-bis(ethylthio)-4-aminopyrimidine (VI), m. 72-3° (petr. ether), b0.5 155-60°. I (8.2 g.) treated with 60 ml. absolute CH2:CHCH2OH and 4 g. Na 2 hrs. at 100° yielded after evaporation in vacuo 2,6-diallyl-4-aminopyrimidine (VII), m. 48-53° (Et2O-petr. ether), b0.5 120-30°. Na (5.5 g.) in 60 ml. HOCH2CH2OMe was heated 3 hrs. at 100° with 16 g. crude I in an autoclave, the mixture evaporated in vacuo, the residue extracted with 500 ml. C6H6, the extract washed neutral with H2O, boiled with active C, filtered, and freed of solvent to give 2,6-bis(β-methoxyethoxy)-4-aminopyrimidine (VIII), m. 84-5° (MeOH-Et2O), and a compound, m. 63-4°. Freshly distilled PhNH2 (92 g.), 150 ml. Et2O, and 100 ml. H2O was treated dropwise with 108 g. ClCO2Et in 50 ml. Et2O at 5°, 54 g. ClCO2Et, then 40 g. NaOH in 60 ml. H2O added by a dropping funnel, the mixture stirred 15 min., the precipitate separated and extracted with Et2O, freed of solvent, and the residue distilled in vacuo to give 90% phenylurethan (IX), b11 145-6°, m. 53° (H2O). To 250 ml. HSO3Cl cooled with an ice-salt mixture was added in 5 g. portions 80 g. IX, the temperature was held at 5° maximum, the mixture stirred 15 min. at 5°, left overnight, heated 1 hr. at 75-80° on a water bath, cooled, poured on ice, the precipitated crystals filtered off, washed with NaHCO3 solution and H2O, extracted in 600 ml. C6H6, and the extract filtered hot gave 46 g. N4-carbethoxysulfanilic chloride (X), m. 103° (C6H6). The aminopyrimidines were converted to compounds of the general formula R3NHC6H4SO2NHC:-N.CR2:N.CR1:CH (Xa) by treatment with 5-10% excess X in 2.5 times absolute C5H5N. The mixture was kept briefly at room temperature, heated 1 hr. at 70-80°, C5H5N evaporated in vacuo, the residue treated with 10% NaHCO3, and the precipitated Na salt dissolved in excess H2O to give, after filtration and acidification of the filtrate, the acylated sulfonamide. V yielded 94% Xa (R1 = EtS, R2 = MeO, R3 = EtOCO) (XI), m. 172-3° (EtOH); III gave 82% Xa (R1 = MeO, R2 = EtS, R3 = EtOCO) (XII), m. 188-9° (EtOH); VI yielded 88% Xa (R1 = R2 = EtS, R3 = EtOCO) (XIII), m. 167-8° (EtOH); VII gave 94% Xa (R1 = R2 = CH2:CHCH2OH, R3 = EtOCO) (XIV), m. 164-5° (EtOH); and VIII yielded 60% Xa (R1 = R2 = MeOCH2CH2O, R3 = MeCO) (XV), m. 164-5° (MeOH). The acylsulfonamides were hydrolyzed by heating 1 hr. in 5 moles N NaOH on a water bath and the cooled solution neutralized by dropwise addition of 50% AcOH to give sulfonamides of the general formula H2NC6H4SO2NHC:N.CR2:N.CR’:CH (XVa). XI yielded 97% XVa (R1 = EtS, R2 = MeO), m. 178-9°; XII gave 75% XVa (R1 = MeO, R2 = EtS), m. 181-2°; XIII gave 94% XVa (R1 = R2 = EtS), m. 176-7°; XIV yielded 90% XVa (R1 = R2 = CH2:CHCH2O), m. 163-4°; and XV gave XVa (R1 = R2 = MeOCH2CH2O) (XVI). XVI was converted to the appropriate Ag salt, m. 262-4° (decomposition). The Ag salt of XVI was treated with H2S and the precipitated Ag2S filtered off, and the solution evaporated in vacuo. The residue was treated with Ac2O in C5H5N 2 days at room temperature and 20 min. on a water bath, freed of solvent, and poured into Na2CO3 solution, filtered, and the filtrate neutralized with AcOH to give XV. The Na salt of XV was not obtained in a pure form.
Monatshefte fuer Chemie published new progress about 3286-55-3. 3286-55-3 belongs to class pyrimidines, and the molecular formula is C5H6ClN3O, Related Products of 3286-55-3.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia