Sodium Carbonate → tert-Butyl 4-(5-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-1,3,4-thiadiazol-2-yl)piperazine-1-carboxylate

温度

120 °C

To a stirred suspension of 1-(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-pyrazole [Intermediate 1] (132 mg, 0.441 mmol) and tert-butyl 4-(5-bromo-1,3,4-thiadiazol-2-yl)piperazine-1-carboxylate (140 mg, 0.401 mmol) in dioxane (2 mL) was added Pd(PPh3)4 (23 mg, 20 μmol) followed by a solution of Na2CO3 (85 mg, 0.802 mmol) in water (0.5 mL). The reaction mixture was purged with nitrogen, sealed, and heated at 120° C. for 30 minutes under microwave irradiation. The reaction mixture was cooled to room temperature, diluted with DCM (20 mL), washed with water (10 mL), then the organic phase was separated and concentrated in vacuo to afford the crude product as a pale brown solid. The crude material was purified by flash chromatography using a 12 g silica cartridge running an EtOAc/heptane gradient to afford the title compound as a pale yellow/off-white solid (138 mg, 78% yield). LC-MS: Rt 1.34 min; MS m/z 443.3 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.65 (d, J=2.53 Hz, 1H), 8.21 (d, J=8.59 Hz, 1H), 7.80 (d, J=1.52 Hz, 1H), 7.66 (d, J=2.02 Hz, 1H), 7.60 (dd, J=8.59, 2.02 Hz, 1H), 6.59-6.62 (m, 1H), 4.05 (s, 3H), 3.51 (s, 8H), 1.43 (s, 9H).

1. customThe reaction mixture was purged with nitrogen
2. customsealed
3. temperatureThe reaction mixture was cooled to room temperature
4. additiondiluted with DCM (20 mL)
5. washwashed with water (10 mL)
6. customthe organic phase was separated
7. concentrationconcentrated in vacuo
8. customto afford the crude product as a pale brown solid
9. customThe crude material was purified by flash chromatography

ORDレコード

ord-83c56f95eab6477bad096092269ba51e

出典データセット

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09040712B2