Oxalyl chloride → 2-[2-(3-chlorophenyl)-ethoxymethyl]-6-fluoro-3H-pyrido[2,3-d]pyrimidin-4-one

To a solution of 2,5-difluoropyridine-3-carboxylic acid (150 mg, 0.94 mmol) in CH2Cl2 (5 ml) at 0° C. was added oxalylchloride (97 μl, 1.13 mmol) dropwise followed by 2 drops of DMF. The reaction mixture was warmed to room temperature and stirred for 4 h. The reaction mixture was concentrated in vacuo and used in the next step without further purification. The crude acid chloride was dissolved in MeCN (5 ml) and N,N-diisopropyl ethyl amine (345 μl, 2.67 mmol) was added followed by 2-[2-(3-chlorophenyl)-ethoxy]-acetamidine hydrochloride salt (222 mg, 0.89 mmol) (prepared as described in example 79.2). The reaction mixture was stirred at room temperature for 16 h and then heated to reflux for an additional 16 h. The reaction mixture was cooled to room temperature and concentrated in vacuo to give a residue which was partitioned between water and ethyl acetate. The organic phases were combined, washed with 1N HCl, sat. NaHCO3, brine, dried over MgSO4, filtered and concentrated in vacuo to give a crude residue which was triturated with ether (3×5 ml) to give the desired product 2-[2-(3-chlorophenyl)-ethoxymethyl]-6-fluoro-3H-pyrido[2,3-d]pyrimidin-4-one (65 mg, 0.19 mmol; 22%) as an off white solid. MS: m/e=334.1 [M+H+].

1. concentrationThe reaction mixture was concentrated in vacuo
2. customused in the next step without further purification
3. dissolutionThe crude acid chloride was dissolved in MeCN (5 ml)
4. stirringThe reaction mixture was stirred at room temperature for 16 h
5. temperatureheated
6. temperatureto reflux for an additional 16 h
7. temperatureThe reaction mixture was cooled to room temperature
8. concentrationconcentrated in vacuo
9. customto give a residue which
10. customwas partitioned between water and ethyl acetate
11. washwashed with 1N HCl, sat. NaHCO3, brine
12. dry with materialdried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customto give a crude residue which
16. customwas triturated with ether (3×5 ml)

ORD 기록

ord-05fd31a4372d444bb343e62bba4dc495

출처 데이터셋

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07572801B2