Ammonia → 7'-Bromo-5-methyl-3',4'-dihydro-2'H-spiro[imidazole-2,1'-naphthalen]-4-amine

Participants

Reaction Conditions

Reaction Steps

7′-Bromo-4-methyl-3′,4′-dihydro-2′H-spiro[imidazole-2,1′-naphthalene]-5(1 H)-thione (Example 51 Step 3, 1 g, 3.23 mmol) was taken up in ammonia (7M in MeOH, 15 mL, 105 mmol) and the resulting mixture was heated in the microwave reactor at 110° C. for 30 min. The solvent was evaporated. Ammonia (7M in MeOH, 15 mL, 105 mmol) was added and the reaction was heated again using MW for 30 min at 110° C. The solvent was evaporated. Ammonia (7M in MeOH, 15 mL, 105 mmol) was added and the reaction was heated again using MW for 30 min at 110° C. The solvent was evaporated and the residue was dissolved in EtOAc (20 mL). The resulting mixture was extracted with 0.1 M citric acid (2×10 mL). The organic layer was discarded while the aqueous phase was basified to pH 12 by addition of 50% NaOH (aq) and extracted with iii DCM (3×20 mL). The organic phase was dried with a phase separator and concentrated in vacuo to give the title compound (0.619 g, 65% yield). 20 mg of the product was purified using flash chromatography (4 g SiO2, DCM in 0.1M NH3 in MeOH) to give the title compound (10 mg). 1H NMR (500 MHz, CDCl3) δ ppm 1.88-1.99 (m, 2 H), 2.07-2.16 (m, 1 H), 2.20 (dqd, 1 H), 2.31-2.37 (m, 3 H), 2.92 (t, 2 H), 6.68 (d, 1 H), 7.04 (d, 1 H), 7.25 (dd, 1 H); 1H NMR (500 MHz, CD3OD) δ ppm 1.84 (ddd, 1 H), 1.94 (ddd, 1 H), 2.03-2.12 (m, 1 H), 2.15 (dtd, 1 H), 2.34 (s, 3 H), 2.91 (t, 2 H), 6.69 (d, 1 H), 7.11 (d, 1 H), 7.29 (dd, 1 H), MS (ES+) m/z 292 [M+H]1.

Provenance & Evidence