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CAS No. : | 64188-97-2 | MDL No. : | MFCD08235178 |
Formula : | C6H7N3O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | MRZUGOPPUMNHGA-UHFFFAOYSA-N |
M.W : | 137.14 | Pubchem ID : | 10749239 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H332-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With ammonium chloride; N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 40℃; for 72h;Inert atmosphere; | Ammonium hydrochloride (4.98 g, 93.2 mmol) was added to 3-aminoisonicotinic acid (9.90g, 71.7 mmol), 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (35.4 g, 93.2 mmol) and N-ethyl-N-isopropylpropan-2-amine (37.5mL, 215.02 mmol) in DMF (100 mL) under nitrogen. The resulting solution was stirred at 40 °C for 72 hours. The mixture was evaporated to provide the crude material. The crude product was purified by flash silica chromatography with elution gradient 5percent MeOH in DCM. Pure fractions were evaporated to dryness to afford 3-aminoisonicotinamide (8.57 g, 87 percent) as a yellow gum. |
77% | With ammonia; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In methanol; N,N-dimethyl-formamide; at 20℃; | To the suspension of isonicotinic acid (1.00 g, 7.24 mmol) in DMF (10 mL) were added HOBt (978 mg, 7.24 mmol), 7 M ammonia solution in methanol (2.06 mL, 14.5 mmol) and EDC*HCl (2.08 g, 10.9 mmol). The mixture was stirred overnight at room temperature. Solvent was distilled off in vacuo, and CH2Cl2 and saturated NaHCO3 aqueous solution were added to the residue. Organic phase was separated, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (5-->8percent MeOH-CH2Cl2) to obtain the title compound (767 mg, 5.60 mmol, 77percent) as a pale yellow powder. 1H NMR (DMSO-d6) delta: 6.59 (2H, br s), 7.39 (1H, d, J = 5.3 Hz), 7.43 (1H, br s), 7.72 (1H, d, J = 5.3 Hz), 8.00 (1H, br s), 8.12 (1H, s). ESI-MS m/z: 138 (M+H)+. |
General method for synthesis of 4-chloropyrido[3,4-d]pyrimidine: The mixture of 3-aminoisonicotinic acid (B-1) (7 g, 50 mmol) and DMF (0.2 mL) in thionyl chloride (100 mL) is stirred at reflux for 2 h. The mixture is then concentrated in vacuo. The residue is dissolved in THF (30 mL) and the resulting solution (solution A) is used directly in the next step. [00676] To a stirred mixture of ammonium hydroxide (100 mL), the above solution A (30 mL) is added dropwise while the reaction temperature is maintained between 25 °C to 30 °C using an ice-water bath. The resulting mixture is stirred at RT for 2 h and then water (100 mL) is added. The organic layer is separated, washed with water (100 mL x 2), dried over Na2S04 and filtered. The filtrate is concentrated in vacuo to afford the amide (B-2). |
With ammonium chloride; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 20℃; for 15h; | General procedure: The syntheses of compounds 3a-3x were mainly referred to literature method [35]. A mixture of 1a-1q, 1w, 1x (2mmol), EDC?HCl (575mg, 3mmol), HOBt (446mg, 3.3mmol), NH4Cl (348mg, 6.5mmol) and DIPEA (2.3mL, 13mmol) in DMSO (7mL) was stirred at room temperature for 15h. The mixture was extracted with EtOAc three times, and the combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford 3a-3q, 3w, 3x. A mixture of 2r-2v (2mmol) and NH3·H2O (25?28wtpercent, 80mmol) in sealed tube was heated at 100°C for 12h. The mixture was cooled to room temperature and extracted with EtOAc three times. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford 3r-3v. | |
Example 2.10; 2-(1-Benzofuran-2-yl)pyrido[3,4-d]pyrimidin-4(3H)-one (C: R=7-aza, R'~1-benzofuran-2-yl); A slurry of 3-aminoisonicotinic acid (1.556 g, 11.3 mmol) and CDI (2.82 g, 17.4 mmol) in dmf (20 mL) was heated to 40°C for 0.5 h then cooled. Concentrated aqueous ammonia (50 mL) was added and the mixture was stirred for 15 min then extracted with ethyl acetate. Removal of the solvent gave a solid which was dissolved in pyridine (20 mL), 1-benzofuran-2-carbonyl chloride (from benzo[ib]furan-2-carboxylic acid; 2.006 g, 12.4 mmol) was added and the mixture was refluxed for 0.5 h, poured onto ice and filtered to give theintermediate amide (E: R=4-aza, R'=1-benzofuran-2-yl). The intermediate amide was refluxed in 5percent aqueous KOH (20 mL)/EtOH (10 ml_) for 0.5 h to give the product (0.303 g, 10percent) as a solid. 1H NMR (DMSO-d6) 5 ppm 13.07 (bs, 1H), 9.15 (d, 1H, J=0.8 Hz), 8.68 (d, 1H, J=5.1 Hz), 8.11 (d, 1H, J=0.8 Hz), 7.98 (dd, 1H, J=5.1, 0.8 Hz), 7.84 (dd, 1H, J=7.5, 0.8 Hz), 7.77 (dd, 1H, J=8.3, 0.8 Hz), 7.51 (ddd, 1H, J=8.3, 7.3, 1.2 Hz), 7.38 (td, 1H, J=7.5, 0.8 Hz). ACPI-MS Found: [M+H]+= 264. |
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