Triethylamine → HCID 68863331, compound

Temperature

0 °C

A mixture of oxo-(1,3,5-trimethyl-1H-pyrazol-4-yl)-acetic acid (134 mg, 0.87 mmol) in dichloromethane (4.0 mL) at 25° C. was treated with triphenylphosphine (145 mg, 0.55 mmol). The reaction was cooled to 0° C. and was treated with N-chlorosuccinimide (74 mg, 0.55 mmol). This mixture was stirred at 0° C. for 30 min and then was warmed to 25° C. for 20 min. At this time, the reaction was treated with 3-cyclopropylmethyl-1-(2-fluoro-benzyl)-8-(4-methylamino-benzyl)-3,7-dihydro-purine-2,6-dione (290 mg, 0.69 mmol) and triethylamine (0.23 mL, 1.67 mmol). The reaction was stirred at 25° C. for 24 h. At this time, the reaction was diluted with dichloromethane and then was washed with a 1N aqueous hydrochloric acid solution (2×50 mL) followed by a saturated aqueous sodium bicarbonate solution (2×50 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 2:98 methanol/dichloromethane) afforded impure product. The resulting residue was purified by HPLC (15–60% acetonitrile/water (0.075% trifluoroacetic acid in both solvents) over 40 min). Fractions with the desired product were combined and concentrated in vacuo. The resulting residue was diluted with dichloromethane (50 mL) and was washed with a saturated aqueous sodium bicarbonate solution (50 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting solid was dried in vacuo for 24 h to afford N-{4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-N-methyl-2-oxo-2-(1,3,5-trimethyl-1H-pyrazol-4-yl)-acetamide (183 mg, 45.8%) as a white solid: (ES)+-HRMS m/e calcd for C32H32N7O4F (M+H)+ 598.2573, found 598.2578.

1. temperaturewas warmed to 25° C. for 20 min
2. stirringThe reaction was stirred at 25° C. for 24 h
3. washwas washed with a 1N aqueous hydrochloric acid solution (2×50 mL)
4. dry with materialThe organics were dried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customFlash chromatography (Merck Silica gel 60, 230–400 mesh, 2:98 methanol/dichloromethane) afforded impure product
8. customThe resulting residue was purified by HPLC (15–60% acetonitrile/water (0.075% trifluoroacetic acid in both solvents) over 40 min)
9. concentrationconcentrated in vacuo
10. additionThe resulting residue was diluted with dichloromethane (50 mL)
11. washwas washed with a saturated aqueous sodium bicarbonate solution (50 mL)
12. dry with materialThe organics were dried over magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customThe resulting solid was dried in vacuo for 24 h

ORD record

ord-571d71ec44254934860739a518296f91

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07135475B2