Pyridine → HCID 135931653, compound

Participants

Reaction Conditions

Reaction Steps

3-Methyl-4-oxo-4,7-dihydroisothiazolo[5,4-b]pyridine-5-carboxylic acid (100.0 mg, 475.7 μmol) and 3-tert-butyl-1H-indol-6-amine (89.56 mg, 0.4757 mmol) were added to a 20-mL vial and suspended in 2-methyl THF (1 mL), followed by propane phosphonic acid anhydride (T3P®, 50% solution in ethyl acetate, 757 mg, 1.19 mmol). Pyridine (75.26 mg, 76.95 μL, 951.4 μmol) was then added and the solution heated at 45° C. for 16 h. The reaction was diluted with 5 mL ethyl acetate and washed with water (1×10 mL). The organic layer was pulled off and concentrated. The residue was dissolved in 6 mL DMF and HPLC purified (RP-C18, 20-99% CH3CN/0.05% TFA). The pooled product fractions were concentrated to approximately 5 mL to provide a suspended white solid. The suspended material was filtered, washed with water and air dried to yield the product N-(3-tert-butyl-1H-indol-6-yl)-3-methyl-4-oxo-4,7-dihydroisothiazolo[5,4-b]pyridine-5-carboxamide (60 mg, 33% yield) as an off-white solid. LC/MS m/z 381.0 [M+H]+, retention time 1.79 min (RP-C18, 10-99% CH3CN/0.05% TFA over 3 min). 1H NMR (400 MHz, DMSO-d6) δ 13.11 (s, 1H), 12.27 (s, 1H), 10.73 (s, 1H), 8.92 (s, 1H), 8.11 (d, J=1.7 Hz, 1H), 7.65 (d, J=8.6 Hz, 1H), 7.02 (dd, J=9.5, 0.9 Hz, 1H), 6.98 (d, J=2.3 Hz, 1H), 2.79 (s, 3H), 1.40 (s, 9H).

Provenance & Evidence