Water → (R)-tert-butyl 2-(2-chloro-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)acetate

Sodium hydride (60% in oil, 19.41 mg, 0.485 mmol) was added to a solution of (R)-2-chloro-5,6,6a,7,9,10-hexahydro-[1,4]oxazino[3,4-h]pteridine (PREPARATION x3, 100 mg, 0.441 mmol) in DMF (1 mL) at 0° C. The resulting mixture was stirred at room temperature for 30 minutes, after which tert-butyl bromoacetate (0.078 mL, 0.529 mmol) was added at 0° C. The reaction mixture was stirred at room temperature for 30 minutes. Water was added and the mixture was extracted with EtOAc, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by column chromatography (SiO2, 20-80% EtOAc/hexane gradient) to afford the title compound as an off-white solid (101 mg, 67.2%). 1H NMR (400 MHz, CDCl3) δ 1.44-1.49 (m, 9H), 3.01-3.11 (m, 1H), 3.15-3.29 (m, 2H), 3.37 (dd, J=11.37, 8.84 Hz, 1H), 3.58 (td, J=11.94, 2.91 Hz, 1H), 3.64-3.76 (m, 2H), 3.88-4.07 (m, 3H), 4.53 (dd, J=13.89, 2.02 Hz, 1H), 7.22 (s, 1H). ESI-MS m/z [M+H]+ calc'd for C15H21ClN4O3, 341.13. found 341.2

1. stirringThe reaction mixture was stirred at room temperature for 30 minutes
2. extractionthe mixture was extracted with EtOAc
3. washwashed with brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by column chromatography (SiO2, 20-80% EtOAc/hexane gradient)

ORDレコード

ord-e884e120e8314b8b91d0c517d8601f0e

出典データセット

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08791107B2