Sodium triacetoxyborohydride → 5-(1-(3-(Methoxymethyl)-3-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)pyrrolidin-1-yl)ethyl)-1,3-dimethyl-1H-benzo[d]imidazol-2(3H)-one

Participants

Reaction Steps

The title compound was prepared according to general procedures described in Scheme 6: A mixture of (3-(methoxymethyl)pyrrolidin-3-yl)(3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)methanone VIc (50 mg, 0.146 mmol), 5-acetyl-1,3-dimethyl-1H-benzo[d]imidazol-2(3H)-one (30 mg, 0.146 mmol) and Ti(OiPr)4 (51 mg, 0.182 mmol) in THF (2.5 mL) was irradiated in a Microwave instrument at 100° C. for 30 min (Personal Chemistry Emrys™ Optimizer microwave reactor). The reaction mixture was cooled and NaBH(OAc)3 (93 mg, 0.438 mmol) was added. The mixture was stirred at room temperature overnight. The solvent was removed in vacuo. The residue was dissolved in 30 mL of ethyl acetate and washed with sat. NaHCO3. The organic layer was washed with brine (×3), then dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by reverse phase preparative HPLC to yield the desired final product as trifluoroacetic salt with purity greater than 95% (18.0 mg, 23.2% yield): 1H NMR (300 MHz, CD3Cl3): δ 8.71 (s, 1H), 7.72 (s, 1H), 7.29 (bs, 1H), 7.01 (bs, 1H), 6.92 (s, 1H), 5.23 (m, 2H), 4.87 (m, 1H), 4.73 (m, 1H), 4.10-3.86 (m, 4H), 3.71 (m, 1H), 3.40 (m, 3H), 3.32-3.24 (m, 6H), 3.12 (m, 3H), 2.91 (bs, 1H), 2.66 (d, 1H), 2.42 (s, 1H), 2.30 (s, 1H), 1.81 (m, 2H); MS (ESI) m/z: Calculated for C27H32F3N5O3: 531.3. found: 532.0 (M+H)+.

Provenance & Evidence