2-Methyl-3-butyn-2-ol → 4-Dimethylamino-9-(3-hydroxy-3-methyl-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester

Temperature

80 °C

To a stirred mixture of 9-Bromo-4-dimethylamino-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester (120 mg, 0.31 mmol) in TEA (5 mL) and DMF (1 mL) were added Pd(OAc)2 (7.0 mg, 0.03 mmol), PPh3 (24.6 mg, 0.09 mmol), CuI (11.9 mg, 0.06 mmol), 2-methylbut-3-yn-2-ol (131.5 mg, 1.56 mmol). The reaction mixture was degassed with N2 and heated in autoclave at 80° C. overnight. Then the mixture was cooled to room temperature, and EtOAc was added. The mixture was filtered though Celite, and the filtrate was washed with saturated brine, dried over Na2SO4, filtered, concentrated in vacuo, and purified by flash column chromatography (silica gel, EtOAc in hexane from 10% to 20%) to afford 4-Dimethylamino-9-(3-hydroxy-3-methyl-but-1-ynyl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester (50 mg, 41%) as a light yellow solid. LC-MS (ESI & APCI): 387.5 (M+1).

1. customThe reaction mixture was degassed with N2
2. temperatureThen the mixture was cooled to room temperature
3. additionEtOAc was added
4. filtrationThe mixture was filtered though Celite
5. washthe filtrate was washed with saturated brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. custompurified by flash column chromatography (silica gel, EtOAc in hexane from 10% to 20%)

ORD record

ord-87e92b96b9fa468ebf207725be77c96f

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09034866B2