Cesium carbonate → 3,5-Dichloro-4-[4-(6-ethylpyrimidin-4-ylamino)thiazolo[5,4-c]pyridin-2-yl]-benzonitrile

온도

70 °C

A mixture of 4-(4-bromothiazolo[5,4-c]pyridin-2-yl)-3,5-dichlorobenzonitrile (0.095 g, 0.25 mmol), 6-ethylpyrimidin-4-ylamine (29 mg, 0.23 mmol), Pd2(dba)3 (11 mg, 0.012 mmol), XantPhos (14 mg, 0.025 mmol) and cesium carbonate (0.201 g, 0.62 mmol) in dioxane (2.5 mL) was degassed with a stream of nitrogen. The reaction mixture was heated at 70° C. for 16 hours. After cooling to room temperature, the resultant mixture was diluted with water and filtered through Celite® washing with DCM. The aqueous phase was further extracted with DCM and the combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The resultant residue was purified by silica gel flash C18 column chromatography eluting with 0-100% EtOAc in pentane followed by a 20-60% gradient MeOH in H2O+1M HCl (1.25 mL in each 25 mL of eluent). The product containing fractions were combined and concentrated under reduced pressure. The resultant solid was suspended in a mixture DCM/EtOAc/MeOH and washed with a saturated solution of NaHCO3, then dried and concentrated under reduced pressure. Further column chromatography purification on silica gel, eluting with 0-50% EtOAc in DCM, afforded the title compound as a pale yellow solid (30 mg, 28% yield). 1H NMR (400 MHz, DMSO-d6): δ 10.70 (br s, 1H), 8.66 (d, J=1.2 Hz, 1H), 8.46 (d, J=5.6 Hz, 1H), 8.39 (s, 2H); 7.84 (d, J=5.6 Hz, 1H), 7.56 (s, 1H), 2.67 (q, J=7.6 Hz, 2H), 1.23 (t, J=7.6 Hz, 3H). LCMS (Method C): RT=3.81 min, m/z: 427 [M+H+].

1. customwas degassed with a stream of nitrogen
2. temperatureAfter cooling to room temperature
3. additionthe resultant mixture was diluted with water
4. filtrationfiltered through Celite®
5. washwashing with DCM
6. extractionThe aqueous phase was further extracted with DCM
7. dry with materialthe combined organic layers were dried (MgSO4)
8. concentrationconcentrated under reduced pressure
9. customThe resultant residue was purified by silica gel flash C18 column chromatography
10. washeluting with 0-100% EtOAc in pentane
11. additionThe product containing fractions
12. concentrationconcentrated under reduced pressure
13. washwashed with a saturated solution of NaHCO3
14. customdried
15. concentrationconcentrated under reduced pressure
16. customFurther column chromatography purification on silica gel
17. washeluting with 0-50% EtOAc in DCM

ORD 기록

ord-b9347fbc2d1f439fb0b87974dc39c21e

출처 데이터셋

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08697708B2