Dimethylformamide → HCID 59497377, compound

Temperature

120 °C

A reaction tube was charged with 6-bromo-1H-indole-4-carboxylic acid methyl ester (635 mg, 2.5 mmol) and Pd(PPh3)4 (15.7 mg, 0.06 mmol) followed by DMF (8 mL), trimethylboroxine (1.3 mL, 9.5 mmol), and an aqueous solution of Na2CO3 (2.75 mL, 4M, 11 mmol). The tube was sealed and the reaction mixture was heated in the microwave at 120° C. for 80 m. The reaction mixture was diluted with water (25 mL) and ethyl acetate (25 mL), filtered, and the mother liquors were isolated and washed with water (2×25 mL) and brine (1×25 mL), dried and concentrated. The residue was purified by flash chromatography using a gradient of ethyl acetate and hexane. The intermediate, 6-methyl-1H-indole-4-carboxylic acid methyl ester (238 mg, 50% yield) was isolated by evaporation of the solvent. A solution of this intermediate (238 mg, 1.26 mmol) in THF (10 mL) was cooled to 0° C. and LAH (77 mg, 2.0 mmol) was added in portions under an atmosphere of N2. The reaction mixture was stirred at 0° C. for 2 h, then at ambient temperature for 18 h. An additional portion of LAH (40 mg, 1.05 mmol) was added and the reaction mixture was stirred an additional 3 h then added to a saturated solution of NaHCO3 in portions. After stirring for 15 m, the mixture was extracted with ethyl acetate (3×15 mL) and the combined extracts were washed with brine, dried and concentrated to 174 mg of crude 6-methyl-1H-indol-4-yl)-methanol which was used directly. This intermediate was converted to the title compound using methods similar to those described in Example 31. LCMS (ESMS): m/z 392 (M+H).

1. customThe tube was sealed
2. filtrationfiltered
3. customthe mother liquors were isolated
4. washwashed with water (2×25 mL) and brine (1×25 mL)
5. customdried
6. concentrationconcentrated
7. customThe residue was purified by flash chromatography

ORD record

ord-3aa75535925e4f9ab6a999cc25fed87d

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09150556B2