反应 #122

ord-f766bf8ef3f8450eb6d323fd10519896

反应方程式

Clc1cc(I)c(Cl)cn1
Clc1cc(I)c(Cl)cn1
CONC(=O)c1ccccc1N
CONC(=O)c1ccccc1N
CONC(=O)c1ccccc1Nc1cc(Cl)ncc1Cl
CONC(=O)c1ccccc1Nc1c
收率 39.1%

溶剂

反应条件

温度
100°CELSIUS

实验过程

2,5-dichloro-4-iodopyridine (75 g, 273.84 mmol), 2-amino-N-methoxybenzamide (47.8 g, 287.53 mmol), cesium carbonate (107 g, 328.60 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (11.88 g, 20.54 mmol) were suspended in 1,4-dioxane (913 ml). Nitrogen was bubbled through the mixture for 20 minutes then diacetoxypalladium (3.07 g, 13.69 mmol) was added. Reaction was heated to reflux overnight under nitrogen. Reaction was allowed to cool to ~50°C and filtered. Filtered cake was washed with hot EtOH (2x300 mL) _._ Filtrate was concentrated to dryness to afford crude as a black solid (57 g). Filtered cake was re-washed with CH2Cl2/MeOH 9/1 (3x300 mL). Filtrate was combined with previous crude and concentrated to dryness to afford crude as a black solid (93 g). Crude was stirred in boiling EtOH (380 mL). Insoluble was filtered => _seemed to contain expected product / instantaneous cristallisation occured in the filtrate_. Flask was left standing overnight. Resulting crystals were filtered, washed with Et2O (x2) and dried to afford 2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (33.4 g, 39.1%, EN03787-93-02) as a dark grey crystalline solid => _product crystallised with 1eq of EtOH._ Insoluble material was washed with EtOH, CH2Cl2 and dried overnight to afford 2-(2,5-dichloropyridin-4-ylamino)-N-methoxybenzamide (26.6 g, EN03787-93-01) => _not fully soluble in DMSO, seemed contaminated by minerals._ It was suspended in H2O (200 mL) and stirred at room temperature for 20 minutes. It was filtered, washed with EtOH (x2) and dried to afford an orange solid (3.8 g !!) => _not soluble in DMSO, probably only a few expected product in it !!_

来源

750 AstraZeneca ELN dataset