1,4-Dioxane → HCID 66714442, compound

A pressure vessel charged with a mixture of tetrakis(triphenylphosphine) palladium(0) (200 mg, 0.173 mmol), Intermediate 29C (550 mg, 1.735 mmol), potassium phosphate tribasic (1.103 g, 5.2 mmol) and Intermediate 1A (356 mg, 2.6 mmol) was stirred at room temperature for 5 min under a nitrogen atmosphere, followed by addition of 1,4-dioxane (6.7 mL) and water (2.6 mL). The reaction mixture was degassed for 2 min, heated at 85° C. overnight and then cooled to room temperature. The mixture was filtered, and the filtrate was concentrated under reduced pressure. The crude material was purified by preparative HPLC using a PHENOMENEX® Luna 30×100 mm S5 column eluting with aqueous MeOH containing 0.1% TFA, gradient 20 to 70%, gradient time 12 min) The collected fractions were concentrated and then applied on a 1 g MCX cartridge. The cartridge was washed with methanol, and then eluted with 2M solution of ammonia in methanol (30 mL). The evaporation of the collected eluent under reduced pressure provided Intermediate 29 (117 mg, 23.9% yield) as a beige powder. MS (ES): m/z=283.14 [M+H]+. Intermediate 29 was used in the synthesis of Examples 183 and 184.

1. customThe reaction mixture was degassed for 2 min
2. temperatureheated at 85° C. overnight
3. temperaturecooled to room temperature
4. filtrationThe mixture was filtered
5. concentrationthe filtrate was concentrated under reduced pressure
6. customThe crude material was purified by preparative HPLC
7. washcolumn eluting with aqueous MeOH containing 0.1% TFA, gradient 20 to 70%, gradient time 12 min) The collected fractions
8. concentrationwere concentrated
9. washThe cartridge was washed with methanol
10. washeluted with 2M solution of ammonia in methanol (30 mL)
11. customThe evaporation of the collected eluent under reduced pressure

ORD record

ord-4cef8790bc1146c6a4bc8d007541dc0a

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08916553B2