反应详情

温度

150 °C

Sodium tert-butoxide (876 mg, 9.12 mmol) was added to a suspension of 2-(4-aminopyrazol-1-yl)acetic acid dihydrochloride (542 mg, 2.53 mmol) in 1,4-dioxane (15 mL). 2-[(2,5-Dichloropyridin-4-yl)amino]-N-methylbenzamide (300 mg, 1.01 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (94 mg, 0.16 mmol) were added and the resulting suspension was purged with nitrogen. Tris(dibenzylideneacetone)dipalladium(0) (74.2 mg, 0.08 mmol) was added and the mixture was again purged with nitrogen. The mixture was heated at 150° C. for 60 minutes in a microwave reactor and then allowed to cool to room temperature. The mixture was evaporated and the residue partitioned between CH2Cl2 (60 mL) and a 0.1N solution of NaOH (60 mL). The aqueous layer was separated, washed with CH2Cl2 (30 mL) and then adjusted to pH4 by the addition of a 2N solution of HCl. The mixture was filtered and the filtrate evaporated. The residue was triturated with a 1:1 mixture of CH2Cl2/MeOH (150 mL), filtered and the solid washed with a 1:1 mixture of CH2Cl2/MeOH (3×150 mL). The combined filtrates were evaporated to afford 2-[4-[[5-chloro-4-[[2-(methylcarbamoyl)phenyl]amino]pyridin-2-yl]amino]pyrazol-1-yl]acetic acid (300 mg, 74% yield) which was used in the next step without further purification; 1H NMR spectrum: (300 MHz, DMSO) δ 2.78 (3H, d), 4.41 (2H, s), 6.68 (1H, s), 7.10 (1H, dd), 7.28 (1H, s), 7.51 (1H, dd), 7.57 (1H, d), 7.73 (1H, d), 7.77 (1H, s), 7.98 (1H, s), 8.66 (1H, s), 8.75 (1H, q), 10.04 (1H, s); Mass spectrum: m/z (ESI+) (M+H)+=401.3 and 403.3.

1. customthe resulting suspension was purged with nitrogen
2. customthe mixture was again purged with nitrogen
3. temperatureto cool to room temperature
4. customThe mixture was evaporated
5. customthe residue partitioned between CH2Cl2 (60 mL)
6. customThe aqueous layer was separated
7. washwashed with CH2Cl2 (30 mL)
8. additionadjusted to pH4 by the addition of a 2N solution of HCl
9. filtrationThe mixture was filtered
10. customthe filtrate evaporated
11. customThe residue was triturated with a 1:1 mixture of CH2Cl2/MeOH (150 mL)
12. filtrationfiltered
13. washthe solid washed with a 1:1 mixture of CH2Cl2/MeOH (3×150 mL)
14. customThe combined filtrates were evaporated