Sodium Carbonate → HCID 58998394, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of 7-Fluoro-6-methylamino-2-(4-nitro-phenyl)-2H-isoquinolin-1-one (100 mg, 0.27 mmol) (Example 104) in DMF (3 mL) was added N-chlorosuccinimide (76 mg, 0.57 mmol). After 18 hours all starting material was consumed. Tin dichloride dehydrate 244 mg (0.11 mmol) was added to the reaction mixture, and the reaction was heated to 80° C. for 2 hr. Upon cooling the reaction mixture was treated with 1 mL of 10% sodium carbonate and extracted 3 times with EtOAc. The combined organic layers were dried over Na2SO4 anhydrous and concentrated in vacuo to give a mixture of the 5-Cl and 4,5-dichloro anilines. This mixture was coupled directly with 76 mg (0.28 mmol) of (5-Chloro-thiophene-2-sulfonyl)-carbamic acid ethyl ester (Example 12) in toluene (0.54 mL) and refluxed for 4 h. The resulting mixture of monochloro and dichloro sulfonylureas were separated by preparative RP-HPLC to give 9.4 mg (6% yield overall) of 5-chloro-N-[({4-[5-chloro-7-fluoro-6-(methylamino)-1-oxoisoquinolin-2(1H)-yl]phenyl}amino)carbonyl]thiophene-2-sulfonamide. ES-MS (M+H)+=541.3 (2Cl).

Provenance & Evidence