Sodium Carbonate → 5-(2-Methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-1,3,4-thiadiazol-2-amine

Temperature

80 °C

To a stirred suspension of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (137 mg, 0.660 mmol) and 5-(4-iodo-2-methoxyphenyl)-1,3,4-thiadiazol-2-amine (200 mg, 0.6 mmol) in dioxane (4 mL) was added Pd(PPh3)4 (35 mg, 0.03 mmol) followed by a solution of Na2CO3 (191 mg, 1.801 mmol) in water (1 mL). The reaction was purged with nitrogen then heated at 80° C. for 18 hours. The reaction mixture was diluted with MeOH (20 mL), filtered through celite, and rinsed with DCM (20 mL). The filtrate was concentrated in vacuo to afford the crude product as an orange oily residue. The crude product was pre-absorbed onto silica gel and purified by flash chromatography using a 24 g silica cartridge, running a MeOH/DCM gradient to afford the title compound as a pale yellow solid (107 mg, 62% yield). LC-MS: Rt 0.81 min; MS m/z 288.1 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.27 (s, 1H), 8.05 (d, J=8.08 Hz, 1H), 7.98 (s, 1H), 7.36 (d, J=1.52 Hz, 1H), 7.28 (dd, J=8.08, 1.52 Hz, 1H), 7.13 (s, 2H), 3.99 (s, 3H), 3.88 (s, 3H).

1. customThe reaction was purged with nitrogen
2. additionThe reaction mixture was diluted with MeOH (20 mL)
3. filtrationfiltered through celite
4. washrinsed with DCM (20 mL)
5. concentrationThe filtrate was concentrated in vacuo
6. customto afford the crude product as an orange oily residue
7. customThe crude product was pre-absorbed onto silica gel
8. custompurified by flash chromatography

ORD record

ord-8d37739cd6494238b13e5fcc01abdccf

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09040712B2