Sodium Carbonate → tert-Butyl 2-(5-(4-(benzyloxy)-2,3-difluorophenyl)-1,3,4-thiadiazol-2-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate

온도

100 °C

Nitrogen was bubbled through a stirred solution of (4-(benzyloxy)-2,3-difluorophenyl)boronic acid (356 mg, 1.349 mmol) and tert-butyl 2-(5-bromo-1,3,4-thiadiazol-2-yl)-2,7-diazaspiro[3.5]nonane-7-carboxylate (343 mg, 0.881 mmol) in dioxane (8 mL). To this solution was added Pd(PPh3)4 (52 mg, 0.045 mmol) followed by a solution of Na2CO3 (286 mg, 2.7 mmol) in water (2 mL). The reaction mixture was sealed and heated at 100° C. for 1 hour under microwave irradiation. The reaction mixture was diluted with EtOAc (150 mL) and washed with water (75 mL). The organic phase was separated, dried over MgSO4, and filtered. The filtrate was concentrated in vacuo to afford the crude product as a light orange/brown solid. The crude material was pre-absorbed onto silica gel and purified by flash chromatography using a 40 g silica cartridge running an EtOAc/heptane gradient to afford the title compound as a white solid (169 mg, 35% yield). LC-MS: Rt 1.62 min; MS m/z 529.4 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ 7.75-7.82 (m, 1H), 7.46-7.51 (m, 2H), 7.36-7.45 (m, 3H), 7.24-7.32 (m, 1H), 5.30 (s, 2H), 3.89 (s, 4H), 3.24-3.31 (m, 4H), 1.66-1.78 (m, 4H), 1.40 (s, 9H).

1. customThe reaction mixture was sealed
2. washwashed with water (75 mL)
3. customThe organic phase was separated
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationThe filtrate was concentrated in vacuo
7. customto afford the crude product as a light orange/brown solid
8. customThe crude material was pre-absorbed onto silica gel
9. custompurified by flash chromatography

ORD 기록

ord-24dabc6b1f344be3a436b96daf0f84d5

출처 데이터셋

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09040712B2