4-Hydroxybenzaldehyde → HCID 178487361, compound

Participants

Reaction Conditions

Reaction Steps

To 1,1-dimethylethyl 4-({[2-(5-amino-3-methyl-1H-pyrazol-4-yl)-6-(methyloxy)phenyl]oxy}methyl}piperidine-1-carboxylate (397 mg, 0.95 mmol) was added 4-hydroxybenzaldehyde (174 mg, 1.4 mmol) and TFA (5 mL). The mixture was heated to 75° C. and stirred for 15 h. After cooling to rt, the volatile materials were removed in vacuo. The resulting residue was dissolved in a 1:1 mixture of water:acetonitrile and purified by preparative HPLC. The fractions containing the desired product were concentrated and lyophilized to provide 4-{1-methyl-8-(methyloxy)-9-[(piperidin-4-ylmethyl)oxy]-3H-pyrazolo[3,4-c]isoquinolin-5-yl}phenol trifluoroacetate (64.1 mg, 0.12 mmol, 13% yield). 1H NMR (400 MHz, DMSO-d6): δ9.81 (br s, 1H), 8.53 (br d, 1H), 8.21 (br m, 1H), 7.84 (d, 1H), 7.43 (m, 2H), 7.38 (d, 1H), 6.92 (m, 2H), 3.97 (s, 3H), 3.88 (d, 2H), 3.32 (br d, 2H), 3.00-2.92 (q, 2H), 2.80 (s, 3H), 2.26 (m, 1H), 2.04 (br d, 2H), 1.52-1.43 (m, 2H); MS (EI) for C24H26N4O3: 419 (MH+).

Provenance & Evidence