Formaldehyde → HCID 67364550, compound

Participants

Reaction Steps

To a solution of 1,2,3,4-tetrahydro-isoquinoline-7-sulfonic acid [1-(3-cyanobenzyl)-2-oxopyrrolidin-3-(S)-yl]amide (0.29 g, 0.71 mmol) in 10 mL of CH2Cl2 is added 0.27 mL of 37% aqueous formaldehyde. The solution is stirred at room temperature for 1 hour. After this time, sodium triacetoxyborohydride (0.05 g, 0.22 mmol) is added and the resulting mixture is stirred for 18 hours. The reaction mixture is diluted with CH2Cl2 and washed with saturated NaHCO3 solution. The organic phase is dried over anhydrous MgSO4, filtered and concentrated to give 2-methyl-1,2,3,4-tetrahydro-isoquinoline-7-sulfonic acid [1-(3-cyanobenzyl)-2-oxopyrrolidin-3-(S)-yl]amide (0.16 g, 0.71 mmol) as a solid. The crude methylated material is then converted to the title compound as described in EXAMPLE 24, Part C. The imidate intermediate is formed over a period of 18 hours at room temperature. The amidine formation occurred upon heating at reflux for 2 hours. The crude product is purified by RP-HPLC eluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 60% CH3CN/H2O (0.1% TFA) and the appropriate product fractions are lyophilized to provide the title compound as a white solid.

Provenance & Evidence