2,4-dichloro-5-ethylpyrimidine

Step A: N, N-DIISOPROPYLETHYLAMINE (195 mL, 0.86 mol) (Aldrich) was added slowly to a mixture of 5-ethyl uracil (52.3 g, 0.37 mol) (from Example LC, suprn) and phosphorous oxychloride (150 mL, 1.61 mol) (Aldrich) with external cooling in a cold water bath. The mixture was heated at reflux for 3.8 hours and cooled to room temperature. Mixture was then poured into ice (300 g). Ethyl acetate (100 mL) was added and mixture stirred at 20 °C for 30 minutes with cooling in an ice-water bath. The resulting mixture was filtered through CELITEE and the filtrate extracted with ethyl acetate-hexanes (1: 1, 3 X 300 mL). The combined organic layers was washed with water (250 mL), dried over sodium sulfate, filtered and concentrated to dryness. This residue was dissolved in ethyl acetate- hexanes (1 : 1) and filtered through TLC grade silica gel and eluting with the same solvent. The filtrate was concentrated to dryness to give 2, 4-dichloro-5-ethyl-pyrimidine. (Yield 56.3 g, 85.2percent).Compound 36. A mixture of compound 34 (100 mg, 234 mumol, 1 eq.), compound 35 (62 mg, 352 mumol, 1.5 eq.), Pd(PPh3)4 (27 mg, 23 mumol, 0.1 eq.), and LiCl (20 mg, 469 mumol, 2 eq.) in toluene (1 mL) was degassed and purged with N2 for 3 times. Then the mixture was stirred at 100 C for 5 h under N2. The reaction mixture was cooled down to 25 C and poured into sat. KF (10 mL) and stirred for 20 min. Then the mixture was extracted with EtOAc (10 mL x 2). The combined organics were washed with brine (20 mL), dried over Na2SO4, and concentrated in vacuo to afford crude compound 36 (40 mg) as a yellow solid, which was used directly in the next step without further purification.

Molecular Weight:177.03
XLogP3:2.9
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:175.9908036
Monoisotopic Mass:175.9908036
Topological Polar Surface Area:25.8
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes