Methanol tetrahydrofuran water → (+/-)-1-(3-amino-4-cyano-benzyl)-4-(5-chloro-1H-indol-2-ylmethyl)-6-oxo-piperazine-2-carboxylic acid

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Reaction Steps

LiOH monohydrate (380 mg, 9.06 mmol) is added at ambient temperature to a solution containing (±)-2-[4-(3-amino-4-cyano-benzyl)-3-methoxycarbonyl-5-oxo-piperazin-1-ylmethyl]-5-chloro-indole-1-carboxylic acid tert-butyl ester (1.0 g, 1.81 mmol), EXAMPLE 784, Part E, in 1:1:1 THF/MeOH/water (30 mL). After 16 h, HOAc (0.5 mL) is added and the reaction mixture is concentrated in vacuo. The residue is dissolved in CH3CN/water and purified by reverse-phase HPLC [Buffer A: water w/0.1% TFA; Buffer B: CH3CN w/0.1% TFA; Gradient: 0% B to 60% B over 30 min] to provide 378 mg (48%) of the title compound as a white solid. 1H NMR (300 MHz, d6-DMSO) δ3.03 (m, 1H), 3.48 (m, 1H), 3.51 (ABq, ΔAB=69.2 Hz, JAB=16.4 Hz, 2H), 3.78 (d, J=15.9 Hz, 1H), 4.05-4.09 (m, 2H), 5.04 (d, J=15.9 Hz, 1H), 6.41 (m, 2H), 6.58 (s, 1H), 7.04 (dd, J=8.6, 2.0 Hz, 1H), 7.25 (d, J=8.0 Hz, 1H), 7.35 (d, J=8.6 Hz, 1H), 7.51, d, J=2.0 Hz, 1H) ppm; MS (ISP loop): m/z 438 (M+H).

Provenance & Evidence