Cyclopropane → HCID 11591389, compound

Participants

Reaction Steps

To the solution of 4-{2-[7-(2,4-difluoro-phenoxy)-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl]-3-methyl-butoxy}-piperidine-1-carboxylic acid tert-butyl ester 15 (40 mg, 0.07 mmol) in dichloromethane (5 mL) was added 1 mL of TFA and the reaction was stirred at room temperature for 2 hours, at which time the solvent was removed and the crude material was re-suspended in dichloroethane, then carboxaldehyde cyclopropane (7.7 mg, 0.11 mmol), DIEA (39 mL, 0.22 mmol), and triacetoxyborohydride (31 mg, 0.148 mmol) were added. The mixture was stirred at 60° C. for six hours, then diluted with 10 mL of CH2Cl2 and extracted with saturated brine (10 mL). The solvent was removed and the crude oil was loaded onto a silica gel column and eluted with 10% MeOH in CH2Cl2 to yield 4.4 mg of 2-[1-(1-cyclopropylmethyl-piperidin-4-yloxymethyl)-2-methyl-propyl]-7-(2,4-difluoro-phenoxy)-3,4-dihydro-2H-isoquinolin-1-one 16 as a white solid. 1H NMR (CDCl3) δ 0.08 (m, 2H), 0.2 (m, 2H), 0.85 (m, 1H), 0.91 (d, J=6.6 Hz, 3H), 1.01 (d, J=6.6 Hz, 3H), 1.62 (m, 2.5H), 1.70 (m, 1H), 1.87 (m, 2.5H), 2.10 (m, 1H), 2.25 (m 3H), 2.78 (m, 2H), 2.89 (m, 2H), 3.30 (n, 1H), 3.49 (m, 1H), 3.59 (m, 1H), 6.84 (m, 1H), 6.90 (m, 1H), 7.06 (m, 2H), 7.14 (d, J=8.3 Hz, 1H), 7.57 (d, J=2.6 Hz, 1H). ESI [M+1] found 499.3; C29H36F2N2O3 requires 498.27.

Provenance & Evidence