Diisopropylethylamine → (1R,6S)[8-(4,6-Dimethyl-pyrimidin-2-yl)-3,8-diaza-bicyclo[4.2.0]oct-3-yl]-(2-thiophen-2-yl-phenyl)-methanone

A mixture of (1R,6S)8-(4,6-dimethyl-pyrimidin-2-yl)-3,8-diaza-bicyclo[4.2.0]octane (Intermediate 4, 28 mg, 0.13 mmol), 2-thiophen-2-yl-benzoic acid (29 mg, 0.14 mmol), HATU (73.2 mg, 0.19 mmol), diisopropylethylamine (50 mg, 0.38 mmol) was stirred in DMF (4 mL) at room temperature for 2 h. Then the reaction mixture was partitioned between water and ethyl acetate mixture. The organic phase was separated and washed with 1N aq. NaOH (10 mL) and then with water (2×15 mL). The organic phase was dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified on HPLC (basic system) to yield the title compound (31.0 mg, 59.8%). MS (ESI) mass calcd. for C23H24N4OS, 404.53; m/z found, 405.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.60-6.75 (m, 7H), 6.43-6.10 (m, 1H), 4.10-1.78 (m, 16H).

1. customThen the reaction mixture was partitioned between water and ethyl acetate mixture
2. customThe organic phase was separated
3. washwashed with 1N aq. NaOH (10 mL)
4. dry with materialThe organic phase was dried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe crude product was purified on HPLC (basic system)

ORD 기록

ord-14da5031a2a94bfa89f44a85049aa6a5

출처 데이터셋

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08680275B2