Ethyl 5-bromo-2-pyrimidineacetate

To a vial equipped with a stir bar was added ethyl 2-(5-bromopyrimidin-2- yl)acetate (500 mg, 2.04 mmol), cesium carbonate (1000 mg, 6.1 mmol), 3-chlorobenzamide (310 mg, 2.0 mmol), (l-S^^-Nl^-dimethylcyclohexane-l^-diamine (58 mg, 0.41 mmol), and dioxane (10 ml). The reaction mixture was purged with nitrogen, and copper(I) iodide (39 mg, 0.20 mmol) was added. The reaction mixture was purged with nitrogen for 5 min, then sealed and heated to 110 C for 19 h. After 19 h the crude reaction mixture was washed with EtOAc (100 ml x 3) and saturated NaHC03. The combined organics were dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography on silica (0-100% EtOAc/hexanes) to afford ethyl 2-(5-(3- chlorobenzamido)pyrimidin-2-yl)acetate. MS ESI calc'd. [M + H]+ 320, found 320.To a solution of Step 1: Ethyl 2-(5-bremepyrimidira-2-yl)-2-methypropaneate LiHMDS (1 M solution in hexanes, 4.80 mL, 4.80 mmol) was added over about 1 0 min to a solution of Ethyl 2-(5-bromopyrimidin-2-yl)acetate (500 mg, 2.04 mmol) was dissolved in THF (8 mL) and the mixture was cooled to -78C under nitrogen. LDA in THF/heptane/ethylbenzene (2M, 1.25 mL) was added dropwise, then the mixture was stirred for 15 minutes. lodomethane (0.22 mL, 3.53 mmol) was added, then the reaction mixture was warmed to room temperature and stirred for a further 2 h. Water (10 mL) was added and the mixture was extracted with ethyl acetate (20 mL). The aqueous layer was acidified topH 5 with 1 M HC1, then extracted with additional ethyl acetate (2 x 20 mL). The combined organic layers were dried over Na2SO4 and concentrated under vacuum. The residue was purified by silica gel chromatography, eluting with a gradient of 0-50% ethyl acetate in heptane, to afford the title compound (417 mg, 79%) as a yellow oil. oH (500 MHz, CDC13) 8.75 (s, 2H), 4.18 (m, 2H), 4.08 (q, J7.2 Hz, 1H), 1.60 (d, J7.3 Hz, 3H), 1.22 (t, J7.1 Hz, 3H).

Molecular Weight:245.07
XLogP3:1.1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:4
Exact Mass:243.98474
Monoisotopic Mass:243.98474
Topological Polar Surface Area:52.1
Heavy Atom Count:13
Complexity:170
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes