Yield:1009827-04-6 75%

Reaction Conditions:

Stage #1: methyl 5-bromo-2-(methylsulfanyl)pyrimidine-4-carboxylatewith 3-chloro-benzenecarboperoxoic acid in dichloromethane at 20; for 1 h;
Stage #2: methylamine hydrochloridewith N-ethyl-N,N-diisopropylamine in tetrahydrofuran;dichloromethane at 20;

Steps:

1.8

Methyl-5-bromo-2-(methylthio)pyrimidine-4-carboxylate (1.0 eq, 661 mg, 2.52 mmol) was dissolved in CH₂Cl₂ (10 ml), meta-chloro perbenzoic acid (m-cpba, 77% pure grade, 2.5 eq, 1.42 g, 6.34 mmol) was added and the mixture was stirred at room temperature for lhour.To the resulting suspension was added anhydrous THF (10 ml), methylamine hydrochloride (10 eq, 1.7g, 25.18 mmol) and DIEA (10 eq, 4.3 ml, 24.69 mmol) and the mixture stirred at room temperature overnight. The solvents were removed in vacuo prior to adding CH₂CI₂ and a saturated aqueous sodium bicarbonate solution. The two phases were decanted and two further CH₂CI₂ extractions were carried out. The combined extracts were dried over Na₂SO₄ and the solvents evaporated. Purification by flash chromatography on silica gel (20-30% ethylacetate in hexanes) provided methyl 5-bromo-2-(methylamino)pyrimidine-4- carboxylate as an off-white solid (461 mg, 75% yield). LCMS (ES): >95% pure, m/z 246 [M]⁺, 248 [M+2]⁺.

References:

WO2008/28168,2008,A2 Location in patent:Page/Page column 78-79