4-Aminopyridine → HCID 67984089, compound

Participants

Reaction Conditions

Reaction Steps

This compound was synthesized in an analogous manner to compound 21 utilizing 2-(benzyloxy)-N-methoxy-N-methylacetamide in step one. To a solution of 4-aminopyridine (79 mg, 0.836 mmol) in THF (1114 μl) cooled to −78° C. was added LHMDS (836 μl, 0.836 mmol). The reaction was stirred −78° C. for 15 minutes, after which time 4′-(benzyloxymethyl)-2-(methylsulfinyl)-4,5′-bipyrimidin-2′-amine (99 mg, 0.279 mmol) was added as a solution in THF (2 mL). The reaction was warmed to rt and stirred for 1 hour. The reaction was quenched by slow addition of saturated ammonium chloride and the reaction mixture was diluted with EtOAc. The residue was then partitioned between water and EtOAc. The organic layer was washed with brine, dried with sodium sulfate, and concentrated in vacuo. The crude product was purified by reverse-phase HPLC [30-100% organic phase over 15 minutes] followed by Biotage™ silica gel chromatography [10 g SNAP column, 100% DCM to 10% MeOH/DCM] to obtain the desired product as a pale yellow solid (94 mg, 88% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 4.42 (s, 2 H) 4.68 (s, 2 H) 7.07-7.19 (m, 4 H) 7.19-7.31 (m, 4 H) 7.76 (d, J=6.57 Hz, 2 H) 8.34 (d, J=6.06 Hz, 2 H) 8.50-8.64 (m, 2 H) 10.05 (s, 1 H). HRMS (ES+) for C21H19N7O.H+ [MH+]: calculated, 386.1729. found, 386.1731. UV-LC: 100/100% UV purity at 214/254 nm; tR=2.78 minutes over 7.75 minutes.

Provenance & Evidence