2-MERCAPTO-N-METHYLBENZAMIDE → HCID 178485312, compound

Participants

Reaction Conditions

Reaction Steps

3,6-diiodoindazole (250.00 g), 2-mercapto-N-methylbenzamide (118.48 g), Pd2(dba)3 (9.28 g), Xantphos (11.73 g), DMF (2.5 L, 10 mL/g), followed by CsOH were added sequentially to a 5 L four-neck flask equipped with a mechanical stirrer and a temperature probe. The reaction mixture was then stirred. The dark mixture was degassed three times by alternately connecting to house vacuum and then nitrogen. The mixture was heated to 70° C. over a period of 30 minutes and maintained at the same temperature for fours, at which time HPLC of the aliquot indicated that the 3,6-diiodoindazole was less than 3%. After cooling, the mixture was poured into a mixture of 7.5 L of water, 1.25 L of toluene and 1.25 L of CH2Cl2 in a 22 L extractor. The mixture was allowed to stir at ambient temperature overnight. A thick precipitate formed overnight. The mixture was filtered and the cake was sucked dry. The cake was further dried at 35° C. under house vacuum for six hours to afford 216 g of the final product. The mother liquor was then extracted with 1.5 L of EtOAc. After partitioning, the aqueous layer was discarded. The organic layer was washed twice each with 2 L of water and concentrated. The residue was treated with 250 mL of CH2Cl2 and stored overnight. A thick precipitate formed overnight. The mixture was filtered and the cake was sucked dry. The cake was dried at 35° C. under house vacuum overnight to afford 24.71 g of the final product. The combined yield was 241 g of the final product. The material showed satisfactory purity and was used in the next step without further purification.

Provenance & Evidence