Category: 92306-69-9

Fox, Jack F. published the artcilePyrimidine nucleosides. XII. Direct synthesis of 2′-deoxycytidine and its α-anomer, Application of 4-(1H-1,2,3,4-Tetrazol-5-yl)pyrimidine, the publication is Journal of the American Chemical Society (1961), 4066-50, database is CAplus.

The direct synthesis of 2′-deoxycytidine (I) was achieved via the mercuri method involving the condensation of 3,5 di-O-(p-chlorobenzoyl)-2-deoxy-D-ribosyl chloride (II) with mercuri-N-acetylcytosine (III). The α-anomer (IV) of I was also obtained from this reaction. The synthesis of II from 2-deoxy-D-ribose (V) was described. The optical rotations of I and IV, as well as those of their acylated intermediates, did not conform to Hudson’s rules of isorotation. The synthesis of other fully acylated derivatives of 2-deoxy-D-ribofuranose from preformed purine-2-deoxy-D-ribonucleosides also was described. V (20.0 g.) in 380 cc. absolute MeOH treated 20 min. at 27° with 20 cc. 1% HClMeOH, stirred with 10.0 g. Ag₂CO₃, filtered and evaporated, the residue dissolved in C₅H₅N, concentrated, and dissolved in 115 cc. dry C₅H₅N, the solution treated 16 hrs. with cooling with 45 cc. p-ClC₆H₄COCl and diluted with H₂O and CH₂Cl₂, the organic layer worked up, and the sirupy Me 3,5-di-O-(p-chlorobenzoyl)-2-deoxy-D-ribofuranoside dissolved in 150 cc. dry Et₂O, cooled to 0°, treated with 200 cc. cold AcOH (saturated with dry HCl), saturated below 10° with dry HCl, and filtered gave 28.0 g. II, m. 118-20° (decomposition). II (0.005 mole) added with stirring to 0.0025 mole dry III in 40 cc. refluxing xylene, cooled, filtered, and diluted with 300 cc. petr. ether and the precipitate purified gave 0.8 g. 1-[3,5-di-O-(p-chlorobenzoyl)-2-deoxy-α-D-ribosyl]-4-acetamido-2(1H)-pyrimidinone (VI) and β-anomer; the mother liquor gave 0.1 g. unidentified, N-free, crystalline material, m. about 160°. α-and β-VI mixture (0.8 g.) in about 20 cc. hot EtOH when cooled deposited about 0.3 g. α-VI, needles, m. 200-1° with sintering at about 160°, resolidifying, and remelting with effervescence at about 230°; this material recrystallized from about 25 cc. boiling EtOH gave short needles, m. 204.5-205°, becoming turbid at 208°, resolidifying at 210°, and remelting with decomposition at about 245°, [α]²⁵_D -66° (c 0.9, CHCl₃); the mother liquor from the α-VI concentrated to 10 cc. and cooled gave 0.44 g. β-VI, m. 128-30° (hot EtOH), resolidifying and remelting with decomposition and effervescence at about 240°, [α]²⁵_D -19° (c 0.9, CHCl₃). α-VI (250 mg.) in 30 cc. absolute EtOH (saturated at 0° with dry NH₃) heated 12 hrs. at 100° in a sealed tube and worked up gave 100 mg. IV, m. 192-3° (EtOH), [α]²⁵_D -44° (c 0.7, N NaOH); picrate, microscopic prisms, m. 173-5° (decomposition and effervescence) (95% EtOH). β-VI (300 mg.) gave similarly I, m. 199-200° (MeOH and Et₂O); picrate, yellow needles, m. 192-8°. Deoxyadenosine (20.1 g.) dissolved with stirring in about 750 cc. dry C₅H₅N, cooled, treated with stirring dropwise with 28 cc. BzCl, kept 48 hrs. at 37-9°, concentrated in vacuo to about 200 cc., and stirred into about 200 cc. ice and H₂O, and the aqueous layer decanted gave 37 g. glassy solid; the product heated 2 hrs. with stirring on the steam bath with 1700 cc. 2N H₂SO₄ and 500 cc. Bu₂O, the aqueous layer again refluxed 1 hr. with 500 cc. Bu₂O, and the combined organic phases cooled, filtered, and worked up gave 19 g. 3,5-di-O-benzoyl-D-ribose (VII). 2′-Deoxyguanosine benzoylated in a similar manner and the product dissolved in dioxane and refluxed with Bu₂O and 2N H₂SO₄ gave 65% VII. VII (0.056 mole) in 60 cc. dry C₅H₅N and 80 cc. CH₂Cl₂ treated 2 days at room temperature with 17.1 g. Ac₂O, evaporated below 50° in vacuo, poured into iced H₂O, and extracted with CHCl₃, and the extract worked up yielded 22% (crude) 1-O-acetyl-3,5-di-O-benzoyl-2-deoxy-D-ribose, m. 86.5-7.5° (EtOH), [α]²⁶_D -23° (c 2.0, CHCl₃). VII benzoylated in a similar manner gave 15% 1,3,5-tri-O-benzoyl-2-deoxy-D-ribose, needles, m. 110-11° (EtOH), [α]²⁵_D 75° (c 2.54, CHCl₃); the original mother liquor yielded 7% of an isomer, needles, m. 83-6° (EtOH), [α]²⁵_D -20° (c 1.1, CHCl₃). The infrared absorption spectra of I and IV were recorded.

Journal of the American Chemical Society published new progress about 92306-69-9. 92306-69-9 belongs to pyrimidines, auxiliary class Tetrazoles, name is 4-(1H-1,2,3,4-Tetrazol-5-yl)pyrimidine, and the molecular formula is C5H4N6, Application of 4-(1H-1,2,3,4-Tetrazol-5-yl)pyrimidine.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Robba, Max published the artcileCertain derivatives of diazines. II. Reactions of nitriles of diazines, Related Products of pyrimidines, the publication is Ann. Chim. (Paris) (1960), 414, database is CAplus.

Several thioamides, amidoximes, tetrazoles, imino esters, amidines, and imino ketones containing diazine structures were prepared VII (1 g.) and 14 ml. EtOH saturated at 0° with NH₃ then H₂S, refrigerated 16 hrs., the precipitate removed, dried, and crystallized from EtOH gave 90% 4-thiocarbamoylpyridazine, m. 214-15°. 3-Thiocarbamoylpyridazine, m. 168°, and 2-, 4-, and 5-thiocarbamoylpyrimidine (XVI), m. 225°, 236°, and 170°, resp., were similarly prepared 3-Hydroxy-4-cyanopyridazine (XVII) (1 g.), 10 ml. C₅H₅N, and 0.83 g. Et₃N saturated at 0° with H₂S, the precipitate removed after refrigeration 16 hrs., and a 2nd crop obtained by addition of 15 ml. H₂O gave 89% 3-hydroxy-4-thiocarbamoylpyridazine, m. 305°. XV (0.517 g.) in 0.5 ml. H₂O at 40° treated with 0.34 g. NH₂OH.HCl in 1 ml. H₂O and 1.45 g. Na₂CO₃ in 7 ml. H₂O, the mixture heated 1.5 hrs. at 70-5°, and refrigerated 16 hrs. gave 0.51 g. pyrazine-2-amidoxime, m. 185-6°. Pyridazine-3-amidoxine m. 240°, pyridazine-4-amidoxime m. 209°, 3-hydroxypyridazine-4-amidoxime m. 232°, and 4-pyridine-amidoxime m. 186°. Pyrimidine-2-amidoxime, m. 262°, required 2.3 hrs. heating; 3-hydroxypyridazine-4-amidoxime, m. 305°, was recovered after acidification with HOAc. 5-Thiocarbamoyl pyrimidine (XVI) (0.5 g.), 0.25 g. NH₂OH.HCl, 1 g. Na₂CO₃, 15 ml. EtOH, and 8 ml. H₂O refluxed 8 hrs., the mixture concentrated, and refrigerated 24 hrs. yielded pyrimidine-5-amidoxime, m. 165°. I (0.9 g.), 0.65 g. NaN₃, 1.8 ml. HOAc, and 3 ml. iso-PrOH heated 108 hrs. at 150°, refrigerated 16 hrs., the dried precipitate dissolved in 10 ml. H₂O, and acidified with 10% HCl yielded 1.14 g. 3-(5-tetrazolyl)pyridazine (XVIII), m. 307-8°, after sublimation at 210°/0.01 mm. Similarly prepared were: 4-(5-tetrazolyl)pyridazine, m. 237°; 3-hydroxy-4-(5-tetrazolyl)pyridazine, m. 331°; 2-(5-tetrazolyl)pyrimidine, m. 233°; and 4-(5-tetrazolyl)pyrimidine, m. 266°. XII (1 g.), 0.7 g. NaN₃, 0.57 g. NH₄Cl, and 13 ml. HCONMe₂ stirred 7 hrs. at 125-30°, the solvent evacuated, and the residue worked up as for XVIII yielded 0.872 g. 4-(5-tetrazolyl)pyrimidine, m. 257°. XV (1 g.) in 5 ml. EtOH saturated with HCl at 0°, excess HCl and EtOH evacuated, the residue washed with Et₂O, suspended in 5 ml. EtOH, saturated with NH₃ at -15°, added to 3 ml. saturated NaCl at 0°, extracted with Et₂O, and the extract gave 0.84 g. ethyl pyrazinimidate, m. 49-50°, after sublimation. Similarly obtained were: ethyl pyrimidine-4-carboximidate (XIX), m. 29-30°; methyl pyridazine-4-carboximidate, m. 102-3°; methyl pyridazine-3-carboximidate, m. 79-80°; ethyl pyrimidine-5-carboximidate (XX), m. 87°; and ethyl pyrimidine-2-carboximidate hydrochlorides, m. 64-5°. For XIX, the solution was filtered prior to extraction with Et₂O. XIII (1 g.) treated similarly to XV, the residue washed with Et₂O, and the Et₂O evaporated yielded 0.634 g. XX. The residue on crystallization from EtOH yielded 0.607 g. 5-amidinopyrimidine hydrochloride, m. 213°, also obtained by refluxing 1 hr. 0.545 g. XX, 0.19 g. NH₄Cl, 9 ml. EtOH, and 1 ml. H₂O. For preparation of N-monosubstituted diazinoamidines, 0.0085-0.036 mole nitrile was fused with an equimolar amount of amine at 30-75° (130-150° for XVII), an equimolar amount of AlCl₃ added such that a temperature of 140-220° is reached (170-180° for best yields), the mixture cooled, dissolved in H₂O at 80°, the solution filtered, the filtrate washed with Et₂O, and made alk. with 40% NaOH (Na₂CO₃ for XVII); the amidine was recovered by filtration or extraction with Et₂O or CHCl₃ and purified by crystallization or sublimation. The following 2-(N-monosubstituted-amidino)-pyrazines were prepared: phenyl, m. 104°; o-tolyl, m. 131°, p-chlorophenyl, m. 148°; benzyl, m. 118°; α-naphthyl, m. 128°; β-naphthyl, m. 114°; and p-tolyl, m. 137°. 3-(N-Monosubstituted-amidino)pyridazines: phenyl, m. 121°; p-tolyl, m. 133°; benzyl, m. 92°; p-chlorophenyl, m. 152°; β-naphthyl, m. 137-8°. 4-Analogs: phenyl, m. 160; p-tolyl, m. 167°; p-methoxyphenyl, m. 118°; p-chlorophenyl, m. 149°; β-naphthyl, m. 128°. The following pyridazines: 3-hydroxy-4-(phenylamidino), m. 177°; 3-hydroxy-4-(p-tolylamidino), m. 190°; 3-hydroxy-4-(p-methoxyphenylamidino), m. 178°; 3-hydroxy-4-(p-chlorophenyl)amidino, m. 198°; 3-hydroxy-4-(β-naphthyl)amidino, m. 183°; and 3-hydroxy-4-(2-pyridyl)amidino, m. 197°. 2-(Monosubstituted-amidino)pyrimidines: phenyl, m. 117-18°; o-tolyl, m. 92-3°; p-tolyl, m. 128°; p-chlorophenyl, m. 112°; α-naphthyl, m. 154-5°; β-naphthyl, m. 166°; benzyl, m. 80°. 4-Analogs: phenyl, m. 126°; o-tolyl, m. 104°; p-tolyl, m. 134°; benzyl, m. 72°; α-naphthyl, m. 148°; β-naphthyl, m. 152°; and p-chlorophenyl, m. 135°. VII, PhCH₂NH₂, and AlCl₃ gave, in addition to the amidine, 4-(N-benzylcarbamoyl)pyridazine, m. 80-1°, also prepared from 4-carbomethoxypyridazine. AlCl₃ (0.0095 mole) added in portions to 0.0095 mole each XIII and amine in 25 ml. CS₂, the solution refluxed 3-4 hrs., decomposed in ice-HCl, the product taken up in dilute HCl, and liberated with 20% NaOH at 0-5° gave 10-38% yields of the following pyrimidines: 5-(N-phenylamidino), m. 172°; 5-(p-tolylamidino), m. 190°; 5-(p-methoxyphenylamidino), m. 178-9°; 5-(2-pyridylamidino), m. 151°; and 5-(2-thiazolylamidino), m. 162-3°. MeMgI (0.0283 mole) in 20 ml. Et₂O added to 0.0905 mole I in 30 ml. Et₂O, the mixture stirred 3 hrs., 15 g. ice and 3 g. NH₄Cl added after 16 hrs., the Et₂O layer separated, the aqueous layer extracted with Et₂O, the Et₂O extracts washed with NaCl, dried, and concentrated gave 0.64 g. oil, which chromatographed (Al₂O₃) gave 3-acetylpyridazine (XXI), m. 87-8°, and VI. The aqueous phase stirred 1 hr. with 20% HCl below 5°, neutralized with 40% NaOH, and the product taken up in Et₂O gave addnl. XXI in 27% total yield. 4-Acetylpyrimidine, m. 67°, was obtained similarly. VII (1 g.) in 50 ml. Et₂O and 5 ml. C₆H₆ treated with 0.0283 mole MeMgI and the mixture treated as in the preparation of XXI, yielded 71% 4-(iminoacetyl)pyridazine, m. 78-9°. 5-(Iminoacetyl)pyrimidine, m. 180-1°, was prepared similarly. Et₂NH (0.0042 mole) in 5 ml. Et₂O added to 0.0142 mole EtMgBr in 12 ml. Et₂O, the solution refluxed 20 min., cooled, 1 g. III in 5 ml. Et₂O and 2 ml. C₆H₆ added, the mixture refluxed 2 hrs., and worked up as for XXI then chromatographed gave 0.208 g. 2-(diethylcarbamoyl)pyrimidine, m. 35-6°. XII gave 4-(diethylcarbamoyl)pyrimidine, m. 36-7°, and XI.

Ann. Chim. (Paris) published new progress about 92306-69-9. 92306-69-9 belongs to pyrimidines, auxiliary class Tetrazoles, name is 4-(1H-1,2,3,4-Tetrazol-5-yl)pyrimidine, and the molecular formula is C5H4N6, Related Products of pyrimidines.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Robba, Max published the artcileCertain derivatives of diazines. I. Synthesis of nitriles of diazines, SDS of cas: 92306-69-9, the publication is Ann. Chim. (Paris) (1960), 351-79, database is CAplus.

All six possible nitriles of pyridazine, pyrimidine, and pyrazine were prepared by dehydration of the corresponding amides with POCl₃. 3-Cyanopyridazine (I) was prepared in poor yield from 3-bromopyridazine (II) and 2-cyanopyrimidine (III) from 2-pyrimidinesulfonic acid. α-Oxoglutaric acid (230 g.) in 390 ml. boiling H₂O treated in 20 min. with 160 g. NaOH, 280 g. (N₂H₄)₂.H₂SO₄ and 980 ml. H₂O, heated 5 min., and cooled gave 181 g. 3-hydroxy-6-carboxy-4,5-dihydropyridazine, m. 196°, which by reaction with POBr₃ gave II. 2,5-Dimethoxy-2,5-dihydrofurfuryl acetate (10.1 g.) and 40 ml. N H₂SO₄ boiled 1 min., cooled rapidly, 5 ml. N₂H₄.H₂O added, the mixture refluxed 20 min., the mixture extracted with 7% MeOH-Et₂O, and the extract distilled yielded isopropylideneacetylhydrazine, b₇ 135-40°, m. 133°, and 28% 3-(hydroxymethyl)pyridazine (IV), b₇ 140-165°, m. 66° (Et₂O-petr. ether). IV was oxidized to 3-carboxypyridazine, which was esterified quant. with CH₂N₂ to 3-carbomethoxypyridazine (V), m. 139° (Et₂O). V (27 g.) in 27 g. MeOH and 70 g. saturated NH₃MeOH gave after several days 90% 3-carbamoylpyridazine (VI), m. 182° (H₂O). VI (3 g.) and 15 ml. POCl₃ treated after 1 hr. with 15 ml. PhMe, refluxed 1 hr., the solvent evacuated, the residue desiccated 24 hrs., dissolved in 30 ml. saturated Na₂CO₃ at 5°, the solution extracted with Et₂O, the extract dried, and concentrated gave 70% I, m. 43-4° (Et₂O). Subsequent nitriles were prepared similarly. 4-Cyanopyridazine (VII) could not be obtained by dehalogenation of 3-chloro-4-cyanopyridazine. 4-Carbomethoxypyridazine, m. 63°, yielded 65% VII, m. 79-80°. 2-Methylpyrimidine (3.6 g.), 26 g. NaOAc, and 55 ml. HOAc treated at 90° with 24.5 g. Br in 10 ml. HOAc, the mixture heated 45 min., refrigerated 1 hr., 90 ml. H₂O added slowly, cooling continued 16 hrs., the product removed, and the addition of H₂O and cooling repeated gave 7.3 g. total 2-tribromomethyl-5-bromopyrimidine (VIII), m. 131° (CHCl₃). AgNO₃ (4.7 g.), 11 ml. H₂O, 3.9 g. VIII, and 29 ml. HOAc heated 1 hr. on a steam bath, filtered, the residue washed with boiling H₂O, the filtrate acidified with 4 ml. HCl, extracted with CHCl₃, and the extract evaporated gave 70% 2-carboxy-5-bromopyrimidine (IX).H₂O, m. 191-2°; free IX m. 231°; methyl ester m. 148-9°, 2-carbamoyl-5-bromopyrimidine (0.75 g.), m. 209°, 60 ml. EtOH, 30 ml. Et₂O, 1.2 ml. 20% Na₂CO₃, and 1 g. Raney Ni stirred 3 hrs. at 50° under 3 kg. II pressure, filtered, the solvents evaporated and the residue extracted with hot CHCl₃ yielded 50% 2-carbamoylpyrimidine, m. 166-7°, after sublimation, converted to III, m. 42°. 2-Chloropyrimidine (3.6 g.), 4.4 g. NaHSO₃, and 20 ml. H₂O heated 1 hr., evaporated, 2 g. KCN ground in, the mixture heated gently at 3 mm. to 260° in 20 min. then to 300° in 20 min., and maintained at 300° until nitrile distillation ceased gave 21% III. 4-Carbomethoxypyrimidine (X), m. 70-1°, was obtained in 47, 52, or 100% yields from the free acid and MeOH-H₂SO₄, MeOH-HCl, or CH₂N₂, resp. X was converted to 4-carbamoylpyrimidine (XI), m. 197°. XI (5.0 g.) stirred 20 hrs. with 30 ml. POCl₃, refluxed 1 hr. at 135-40°, and extracted similarly to I gave 77% 4-cyanopyrimidine (XII), m. 31°. 5-Cyanopyrimidine (XIII), could not be obtained by reductive diazotization of 4-amino-5-cyanopyrimidine. 5-Carboxypyrimidine (XIV) (25 g.) in 200 ml. Et₂O treated at 0° with half of a 1250 ml. Et₂O solution of CH₂N₂ from 75 g. MeN(NO)CONH₂ and 25 g. addnl. XIV added alternately with the rest of the CH₂N₂ gave after 19 hrs. 100% 5-carbomethoxypyrimidine, m. 84°, converted to XIII, m. 85-6°, via 5-carbamoylpyrimidine, m. 214°. Pyrazinamide (3 g.) and 15 ml. POCl₃ stirred 5 hrs., refluxed 40 min., and worked up gave 90% 2-cyanopyrazine (XV), b₇ 87°, m. 20°. Pyrazinoyl chloride (from pyrazinoic acid and SOCl₂, 1.3 hrs. reflux) and p-anisidine in C₆H₆ gave 2-[N-(4-methoxyphenyl)carbamoyl]pyrazine, m. 149-50°. Similarly prepared was 2-[N-(2-naphthyl)carbamoyl]pyrazine, m. 178-9°.

Ann. Chim. (Paris) published new progress about 92306-69-9. 92306-69-9 belongs to pyrimidines, auxiliary class Tetrazoles, name is 4-(1H-1,2,3,4-Tetrazol-5-yl)pyrimidine, and the molecular formula is C5H4N6, SDS of cas: 92306-69-9.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia