反应详情

温度

90 °C

A mixture of 4-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-6-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (49.6 mg, 0.148 mmol) and 5-amino-3-chloroindazole (26.5 mg, 0.155 mmol) in isopropyl alcohol (2.5 mL, 0.033 mol) in a sealed tube was heated to 90° C. (bath temp.) for 3.5 h. The bath temperature was increased to 105° C., and heating was continued overnight. The bath temperature was increased to 120° C., and heating was continued for 5 d. LC/MS at that time indicated loss of Boc group, i.e., (3-chloro-1H-indazol-5-yl)-[6-(1,2,3,6-tetrahydropyridin-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-amine, C18H16ClN7, MW=365.83. Solvents were evaporated. The reddish residue was suspended in N,N-dimethylformamide (3 mL). N,N-diisopropylethylamine (52 μL, 0.30 mmol) and di-tert-butyldicarbonate (33 mg, 0.15 mmol) were added, and the mixture was stirred at rt for 2 h. DMF was evaporated, water and CH2Cl2 were added, and the insoluble brown material was filtered off and washed with CH2Cl2 and water. The layers of the filtrate were separated; the organic layer was washed with water (2×) and brine and dried over MgSO4. The drying agent was filtered off, and the filtrate was concentrated, redissolved in MeOH, passed a through 0.45 μm filter, and purified by MDP. One obtained the title compound as light tan solid. MS (ES+): m/z 465.9/467.9 (100/38) [MH+]. HPLC: tR=2.7 min (ZQ2000, polar—5 min). 1H NMR (DMSO-d6, 400 MHz): δ=1.43 (s, 9H), 2.37-2.44 (brs, 2H), 3.51-3.58 (mc, 2H), 3.99-4.07 (m, 2H), 6.36 (s, 1H), 6.54 (s, 1H), 7.49 (d, J=8.8 Hz, 1H), 7.55 (d, J=8.8 Hz, 1H), 8.05 (s, 1H), 8.12 (s, 1H), 9.21 (s, 1H), 11.88 (brs, 1H), 13.43 (brs, 1H).

1. temperatureThe bath temperature was increased to 105° C.
2. temperatureheating
3. temperatureThe bath temperature was increased to 120° C.
4. temperatureheating
5. waitwas continued for 5 d
6. customSolvents were evaporated
7. customDMF was evaporated
8. additionwater and CH2Cl2 were added
9. filtrationthe insoluble brown material was filtered off
10. washwashed with CH2Cl2 and water
11. customThe layers of the filtrate were separated
12. washthe organic layer was washed with water (2×) and brine
13. dry with materialdried over MgSO4
14. filtrationThe drying agent was filtered off
15. concentrationthe filtrate was concentrated
16. dissolutionredissolved in MeOH
17. filtrationfilter
18. custompurified by MDP