Triethylamine → 2-Cyclopropylpyrimidine-4-carbonitrile

Temperature

110 °C

To a solution of 2-cyclopropylpyrimidine-4-carbaldehyde (29.13 g, 196.6 mmol) in N,N-dimethylformamide (200 mL) was added hydroxylamine hydrochloride (13.9 g, 197 mmol) followed by triethylamine (35 mL, 250 mmol) dissolved in N,N-dimethylformamide (40 mL) at room temperature. A 50% solution of propylphosphonic anhydride in N,N-dimethylformamide (140 mL, 230 mmol) was added and the reaction mixture was stirred at 110° C. for 18 h. The reaction mixture was cooled to room temperature and a saturated aqueous solution of sodium bicarbonate was added with ethyl acetate. The mixture was stirred vigorously and solid sodium bicarbonate was added. The mixture was filtered to remove undissolved solids and the layers were separated. The aqueous layer was extracted with ethyl acetate (3×) The combined organics were washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure, and the resulting residue was dried under high vacuum to afford 2-cyclopropylpyrimidine-4-carbonitrile (20.97 g). The material was used without further purification. 1H NMR (400 MHz, CDCl3) δ 1.15-1.22 (m, 4H), 7.36 (s, 1H), 8.76 (s, 1H).

1. temperatureThe reaction mixture was cooled to room temperature
2. stirringThe mixture was stirred vigorously
3. filtrationThe mixture was filtered
4. customto remove undissolved solids
5. customthe layers were separated
6. extractionThe aqueous layer was extracted with ethyl acetate (3×) The combined
7. washorganics were washed with water and brine
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customthe resulting residue was dried under high vacuum

ORD record

ord-36b1a1ed0cf845e891be03d2a0aabed6

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09296745B2