Tetrahydrofuran → 2-Oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepin-3-yl 4-(2-oxo-1,4-dihydroquinazolin-3(2H)-yl)piperidine-1-carboxylate

温度

0 °C

3-Hydroxy-2-oxo-5-phenyl-1-(2,2,2-trifluoroethyl)-2,3-dihydro-1H-1,4-benzodiazepine (40 mg, 0.12 mmol) and p-nitrophenylchloroformate (24.1 mg, 0.12 mmol) were dissolved in tetrahydrofuran (1 mL) under argon, and cooled to 0° C. Triethylamine (15 uL, 0.11 mmol) was added and the reaction stirred for 1.5 h. Additional triethylamine was added (33 uL, 0.24 mmol) along with 3-(4-piperidinyl)-3,4-dihydroquinazolin-2(1H)-one hydrochloride (32 mg, 0.12 mmol). The reaction was warmed to room temperature and stirred overnight. The reaction was concentrated and the residue triturated with methanol. The triturated solid was purified by reverse phase HPLC (C-18, 5% to 95% 0.1% trifluoroacetic acid/acetonitrile in 0.1% aqueous trifluoroacetic acid gradient elution), to yield the title compound (29 mg). MS 592.2181 (M+1)

1. temperatureThe reaction was warmed to room temperature
2. stirringstirred overnight
3. concentrationThe reaction was concentrated
4. customthe residue triturated with methanol
5. customThe triturated solid was purified by reverse phase HPLC (C-18, 5% to 95% 0.1% trifluoroacetic acid/acetonitrile in 0.1% aqueous trifluoroacetic acid gradient elution)

ORDレコード

ord-068710def1de473e8a6e5f54942ffdd2

出典データセット

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07196079B2