Sodium Carbonate → 3-Methoxy-4-(5-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)-1,3,4-thiadiazol-2-yl)phenol

温度

120 °C

To a stirred suspension of tert-butyl(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)dimethylsilane (Intermediate 3) (3.28 g, 9.00 mmol) and 5-bromo-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)-1,3,4-thiadiazol-2-amine (Intermediate 4) (1 g, 6.00 mmol) in dioxane (48 mL) under nitrogen was added Pd(PPh3)4 (0.347 g, 0.30 mmol) followed by a solution of Na2CO3 (1.272 g, 12.00 mmol) in water (12 mL). The resulting mixture was refluxed at 120° C. for 18 hours. The reaction mixture was cooled to room temperature, then diluted with EtOAc (150 mL) and washed with water (100 mL). The organic phase was separated and the aqueous phase re-extracted with EtOAc (150 mL). The combined organics were dried over MgSO4, filtered, and the filtrate concentrated in vacuo to afford an oily brown residue. The residue was suspended in EtOAc (10 mL) and sonicated, then the resulting suspension was filtered under vacuum to afford the crude product as an off-white solid. The crude mixture was purified by flash chromatography using 3% [7M NH3 in MeOH]/DCM as the eluent to afford the title compound as a pale yellow glass-like solid (0.534 g, 23% yield). LC-MS: Rt 0.75 min; MS m/z 377.3 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.99 (br. s., 1H), 7.88 (d, J=8.59 Hz, 1H), 6.54 (d, J=2.53 Hz, 1H), 6.50 (dd, J=8.34, 2.27 Hz, 1H), 4.34-4.25 (m, 1H), 3.86 (s, 3H), 2.94 (s, 3H), 1.59 (dd, J=11.62, 3.03 Hz, 2H), 1.40 (t, J=12.38 Hz, 2H), 1.26 (br. s., 1H), 1.20 (s, 6H), 1.08 (s, 6H).

1. temperatureThe reaction mixture was cooled to room temperature
2. washwashed with water (100 mL)
3. customThe organic phase was separated
4. extractionthe aqueous phase re-extracted with EtOAc (150 mL)
5. dry with materialThe combined organics were dried over MgSO4
6. filtrationfiltered
7. concentrationthe filtrate concentrated in vacuo
8. customto afford an oily brown residue
9. customsonicated
10. filtrationthe resulting suspension was filtered under vacuum
11. customto afford the crude product as an off-white solid
12. customThe crude mixture was purified by flash chromatography

ORDレコード

ord-307eee1dcdce48fcae10f7b004b1dd67

出典データセット

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09040712B2