Dimethylformamide → HCID 136595519, compound

Participants

Reaction Conditions

Reaction Steps

A solution of the product of Example 354 (67.5 mg, 0.015 mmol) in N,N-dimethylformamide (2 mL) was treated with p-toluenesulfonic acid monohydrate (1 mg) and monoorthomalonic acid tetramethyl ester (272 mg, 1.52 mmol). The mixture was heated at 50° C. in an oil bath under a nitrogen atmosphere and the resulting yellow solution was stirred for 3 hrs. At this time, additional ortho ester was added (272 mg, 1.52 mmol) and heating continued for another 5 hrs. The reaction was cooled to room temperature and the solution was concentrated by rotary evaporation in vacuo. The residue was further dried on a vacuum pump, then dissolved in dichloromethane (100 mL) and washed with water (2×50 mL) and brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was chromatographed on silica gel, eluting with 1% methanol/dichloromethane. The resulting impure material was rechromatographed on silica gel, eluting with a gradient of 5% to 7% acetonitrile/dichloromethane to give the title compound (36 mg, 45%). MS (APCI+) m/z 526 (M+H)+. 1H NMR (300 MHz, DMSO-d6) δ 1.05 (d, J=6.62 Hz, 6 H) 1.91 (m, 1 H) 2.77 (br m, 2 H) 3.72 (s, 3 H) 4.40 (s, 2 H) 6.36 (br m, 1 H) 7.45 (t, J=7.35 Hz, 1 H) 7.70 (d, J=9.19 Hz, 1 H) 7.94 (m, 2 H) 8.20 (d, J=8.82 Hz, 2 H) 14.25 (br s, 1 H). A suspension of the product of Example 363 (6.0 mg, 0.0114 mmol) in anhydrous tetrahydrofuran (3 mL) and distilled water (1 mL) was treated with 0.998 N aqueous sodium hydroxide (0.0114 mL, 0.0114 mmol) and the yellow solution mixed for 15 minutes. The solvent was removed under reduced pressure and the residue dried on a vacuum pump to afford the sodium salt of Example 363 (6.1 mg, 98%). 1H NMR (300 MHz, DMSO-d6) δ 1.04 (d, J=5.15 Hz, 6 H) 1.88 (m, 1 H) 2.75 (m, 1 H) 3.72 (s, 3 H) 4.31 (s, 2 H) 5.95 (m, 1 H) 7.08 (m, 1 H) 7.30 (m, 1 H) 7.58 (m, 2 H) 7.95 (m, 1 H) 8.09 (m, 1 H) 16.55 (s, 1 H).

Provenance & Evidence