Diisopropylethylamine → HCID 18180487, compound

Participants

Reaction Steps

5-Bromothiophene-2-carboxylic acid (1.63 g, 7.88 mmol, 1 eq), the product from Step 158d (1.68 g, 7.88 mmol, 1 eq) and HATU (2.97 g, 7.81 mmol, 1 eq) are suspended in 60 mL CH3CN. The mixture is cooled in an ice bath and DIEA (8.2 mL, 47.28 mmol, 6 eq) is added dropwise. The mixture is allowed to warm to room temperature and stirred overnight. EtOAc and satd NaHCO3 are added. The aqueous layer is extracted with EtOAc. The combined organic layers are washed with 1N NaOH, dried over MgSO4, filtered and concentrated. The residue is purified by silica gel chromatography using a Biotage Flash 40S column (90:9:1 CHCl3/MeOH/NH4OH) to provide 1.26 g (49%) of 5-bromo-N-(2-methyl-1-azabicyclo[2.2.2]oct-3-yl)-thiophene-2-carboxamide as a trans/cis mixture of isomers. The p-toluenesulfonic acid salt of the product is made and recrystallized from IPA/ether to give the product as light yellow solid. MS (ESI) for C13H17BrN2OS m/z 328.9/330.9 (M+H)+. Reverse phase HPLC (ZORBAX Eclipse XDB-C8, 4.6 mm×15 cm, 80:12:8 H2O/CH3CN/IPA) revealed a 95:5 trans/cis mixture of isomers.

Provenance & Evidence