Diisopropylethylamine → HCID 89699969, compound

Participants

Reaction Conditions

Reaction Steps

144 mg (0.38 mmol) of HATU and 81 mg (0.63 mmol) of N,N-diisopropylethylamine were added to a solution of 91 mg (0.31 mmol) of the compound of Example 6A and 173 mg (purity 37%, 0.31 mmol) of 3-tert-butyl-5-cyanobenzoic acid [lit.: WO 2008/021388 A1, intermediate E, page 164] in 2.0 ml of DMSO. The reaction was stirred at 25° C. for 16 h. The reaction mixture was then diluted with ethyl acetate and the phases were separated. The organic phase was washed twice with in each case 50 ml of saturated sodium bicarbonate solution and then dried over sodium sulphate. After filtration, the mixture was concentrated under reduced pressure and the residue obtained in this manner was purified by double chromatography on a Biotage system (first run: 25 g Snap column, mobile phase gradient ethyl acetate/hexane, starting with 20% ethyl acetate, then increasing rapidly to 100% ethyl acetate, then ethyl acetate/methanol, from 0% methanol increasing steadily to 50% methanol; second run: 10 g Snap column, mobile phase gradient ethyl acetate/hexane, starting with 20% ethyl acetate, then increasing rapidly to 100% ethyl acetate, then ethyl acetate/methanol, from 0% methanol increasing steadily to 50% methanol). This gave 17.8 mg (11% of theory) of the title compound.

Provenance & Evidence