Cesium carbonate → 4-[1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl]-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine

Temperature

100 °C

To a solution of 3-methyl-5-(1,3-thiazol-5-yl)aniline (63 mg, 0.33 mmol) and the product of Step 1 (100 mg, 0.33 mmol) in degassed 1,4-dioxane (1.3 mL) were added Pd(OAc)2 (7.4 mg, 0.033 mmol), Xantphos (29 mg, 0.050 mmol) and Cs2CO3 (216 mg, 0.66 mmol) and the reaction was heated to 100° C. for 30 minutes. After cooling, the reaction was partitioned between EtOAc (10 mL) and saturated aqueous sodium bicarbonate (10 mL). The layers were separated, and the aqueous phase was extracted with EtOAc (10 mL). The combined organic phases were washed with saturated aqueous sodium chloride (10 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. Purification on silica (30-70% ethyl acetate in hexanes) afforded 4-[1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl]-N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]pyrimidin-2-amine (50 mg, 33%) as a colorless foam. MS ESI: [M+H]+ m/z 456.1.

1. temperatureAfter cooling
2. customthe reaction was partitioned between EtOAc (10 mL) and saturated aqueous sodium bicarbonate (10 mL)
3. customThe layers were separated
4. extractionthe aqueous phase was extracted with EtOAc (10 mL)
5. washThe combined organic phases were washed with saturated aqueous sodium chloride (10 mL)
6. dry with materialdried over anhydrous MgSO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customPurification on silica (30-70% ethyl acetate in hexanes)

ORD record

ord-1b0a3854d4244bf09895a5775f1c20a4

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08759366B2