Lithium Hydroxide → HCID 23598706, compound

Participants

Reaction Steps

A solution containing {6-(Benzenesulfonylamino-methyl)-3-[(isoquinoline-1-carbonyl)-amino]-2-oxo-2,3,4,7-tetrahydro-azepin-1-yl}-acetic acid methyl ester (34) (84 mg, 0.17 mmol) in 4 mL of 3:1 THF/H2O was treated with excess LiOH and stirred for 2.5 h at rt. The solution was acidified and extracted with EtOAc. The EtOAc layer was dried (Na2SO4) and concentrated to give the crude carboxylic acid. A catalytic amount of Pd(Ph3P)4 is added to a solution of (2-ethoxy-5-oxo-furan-3-yl)-carbamic acid allyl ester (0.24 g, 1.0 mmol) and N,N-dimethylbarbituric acid (0.38 g, 2.4 mmol) in CH2Cl2 (5 mL). The solution is stirred for 15 minutes at room temperature after which {6-(Benzenesulfonylamino-methyl)-3-[(isoquinoline-1-carbonyl)-amino]-2-oxo-2,3,4,7-tetrahydro-azepin-1-yl}-acetic acid (0.069 g) is added as a solution in CH2Cl2/DMF (2 mL, 1:1), followed by HOBt (0.126 g, 0.93 mmol) and EDCl (0.18 g, 0.93 mmol). The solution is stirred for 5 hours, diluted with EtOAc, washed with saturated NaHCO3 and brine, dried (Na2SO4), and concentrated in vacuo. The resulting residue us purified over silica (EtOAc/hexane) to afford the desired compound.

Provenance & Evidence