* 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.
INTERMEDIATE 197-Bromopyrido[2,3-fr1pyrazine 2,3-Diamino-5-bromopyridine (2 g, 10.6 mmol) was dissolved in ethanol (25 mL) and glyoxal (5 mL, 40percent in water) was added. After standing for 48 h the mixture was concentrated in vacuo and the residue triturated with diethyl ether to give, after air-drying, the title compound (2.04 g, 92percent) as a pink-brown solid. δH (d6 DMSO) 9.28 (d, IH), 9.20 (d, IH), 9.12 (d, IH), 8.95 (d, IH). LCMS (ES+) 212 (M+H)+, RT 1.98 minutes.
INTERMEDIATE 197-Bromopyrido[2,3-fr1pyrazine 2,3-Diamino-5-bromopyridine (2 g, 10.6 mmol) was dissolved in ethanol (25 mL) and glyoxal (5 mL, 40% in water) was added. After standing for 48 h the mixture was concentrated in vacuo and the residue triturated with diethyl ether to give, after air-drying, the title compound (2.04 g, 92%) as a pink-brown solid. deltaH (d6 DMSO) 9.28 (d, IH), 9.20 (d, IH), 9.12 (d, IH), 8.95 (d, IH). LCMS (ES+) 212 (M+H)+, RT 1.98 minutes.
With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In acetonitrile; at 20℃;
2,3-Diamino-5-bromopyridine (2.00 g) and <strong>[89531-58-8]morpholin-4-ylacetic acid hydrochloride</strong> obtained by the method described in U.S. Pat. No. 6,352,993 (1.34 g) were dissolved in acetonitrile (15 ml). 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.22 g), 1-hydroxybenzotriazole (0.98 g) and N-methylmorpholine (1.29 ml) were added and the mixture was stirred at room temperature overnight. The reaction solution was diluted with chloroform and washed with brine. The organic layer was dried over anhydrous sodium sulfate and then the solvent was evaporated under reduced pressure. The resulting solid was washed with diethyl ether to give the title compound (1.40 g) as a pale yellow solid.MS (ESI) m/z: 315 (M+H)+.1H-NMR (DMSO-d6) delta: 2.52 (4H, t, J=4.6 Hz), 3.62 (4H, t, J=4.6 Hz), 6.01 (2H, s), 7.84 (1H, d, J=2.2 Hz), 7.87 (1H, d, J=2.2 Hz), 9.20 (1H, s).
Preparation of compound 2-3 [97] After the compound 2-2(11 g, 40.54 mmol), and 5-bromopyridine-2,3-diamine (7.6 g, 40.54 mmol) were dissolved in DMSO (200 mL),the mixture was heated at 200C for 12 hours. After cooling to room temperature, the product was washed with distilled water and extracted with EA. After drying with MgSO4 and distilling under reduced pressure, acompound 2-3 (5 g, 11.38 mmol, 28.07 %) was given by column separation.
With 2,4,6-trimethyl-pyridine; HATU; In N,N-dimethyl-formamide; at 0 - 20℃;
To a stirred solution of 5-bromopyridine-2,3-diamine (811.6 mg, 4.18 mmol) and (2S,4S)-1 -tert-butoxycarbonyl-4-methyl-pyrrolidine-2-carboxylic acid (800 mg, 3.48mmol) in DMF (12.00 mL) is added 2,4,6-collidine (1.384 ml_, 10.47 mmol). The reaction mixture is cooled to 0°C before the addition of HATU (1.59 g, 4.18 mmol). The reaction mixture is stirred at room temperature overnight, diluted with water and extracted with ethyl acetate. The Combined extracts are washed with brine, dried over Na2SC>4 and concentrated. The residue is purified by flash column chromatography on silica gel using EtOAc in Hexanes Attorney Docket No. 097546-0171as eluent (10 to 100percent) to afford tert-butyl (2S,4S)-2-[(2-amino-5-bromo-3- pyridyl)carbamoyl]-4-methyl-pyrrolidine-1 -carboxylate (1.28 g, 91.9percent) as a pale yellow foam.LC/MS: m/z = 400.7(M+H+)
5-bromo-N<SUP>3</SUP>-((5-methylisoxazol-3-yl)methyl)pyridine-2,3-diamine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
A 1 L round bottomed flask was charged with 5-bromopyridine-2,3-diamine (16 g), 5-methylisoxazole-3-carbaldehyde (11.3 g), activated 4? molecular sieves (24 g) and THF (500 mL). The solution was heated to reflux at 70 C overnight and then filtered to remove the molecular sieves. All volatiles were removed under vacuum to leave a crude yellow solid which consisted of a mixture of multiple products and excess aldehyde. This material was used directly in the next step without any further purification. The crude was dissolved in EtOH and NaBH4 (1.40 g) was added and the solution was heated to reflux at 85 C for 18 h. Then the reaction was quenched with water and the product was extracted with DCM, dried over Na2SO4, filtered and concentrated down to a red residue. The product was purified (FCC, SiO2, 0-10% MeOH in DCM) to afford the title compound as solid.1H NMR (300 MHz, CDCl3) δ 7.70 (d, 1H), 6.98 (d, 1H), 5.98 (s, 1H), 4.43 (d, 2H), 4.20 (br s, 2H), 3.81 (br s, 1H), 2.45 (s, 3H).
N-(2-amino-5-bromopyridin-3-yl)-1,2,3-thiadiazole-4-carboxamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
754 mg
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 10 - 35℃;
A mixture of 5-bromopyridine-2,3-diamine (723 mg), <strong>[4100-13-4]1,2,3-thiadiazole-4-carboxylic acid</strong> (500 mg), HATU (2050 mg), Et3N (1.6 mL) and DMF (8 mL) was stirred overnight at room temperature. The mixture was diluted with a saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The organic layer was washed with a saturated brine, then dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (754 mg). The title compound was used for the subsequent reaction without being further purified. MS: [M+H]+ 299.9.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
