Formic Acid → HCID 67253080, compound

Participants

Reaction Steps

Sodium 1-amino-4-{7-[(tert-butoxycarbonyl)amino]-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl}cyclohexanecarboxylate (Compound 285B, 50.0 mg, 0.118 mmol) was taken up in MeOH (1.0 mL, 25 mmol) and over the course of about 5 days was treated repeatedly with formaldehyde (52.5 uL, 0.705 mmol) and Formic acid (26.6 uL, 0.705 mmol) followed by several hours of stirring and then sodium cyanoborohydride (73.8 mg, 1.18 mmol) addition. The reaction was eventually driven to completion after which, the reaction mixture became a suspension. This was filtered and the solid washed a little MeOH. The MeOH filtrate was concentrated to yield a waxy white material which was triturated with DCM and filtered. The DCM filtrate was concentrated to a clear oil and dried in vacuo. 1H NMR (400 MHz, CHLOROFORM-d) d 9.52 (s, 1H), 8.10-8.15 (m, 1H), 7.42 (d, J=8.59 Hz, 1H), 4.36 (s, 2H), 3.18 (s, 3H), 2.93 (s, 6H), 2.82 (dd, J=4.67, 8.72 Hz, 1H), 2.23 (t, J=4.55 Hz, 4H), 1.97-2.07 (m, 2H), 1.83-1.94 (m, 2H), 1.50 (s, 9H). MS (ES+): m/z=432.2303 [MH+]. HPLC: tR=1.12 min (UPLC TOF, polar—3 min). The crude product was taken up in DCM and treated with TFA, stirred for 15 min. The reaction mixture was concentrated to an oil and used without further purification and characterization.

Provenance & Evidence