反应详情

Trifluoroacetic acid (0.67 ml) was added to a dichloromethane (2.0 ml) solution of 5-(2-amino-6-chloropyrimidin-4-yl)-2,4-dimethylbenzoic acid tert-butyl ester (100 mg, 0.33 mmol) obtained in Step 4 of Example 1-1. The mixture was stirred at room temperature for four hours, and then concentrated under reduced pressure. The resulting white solid material was dissolved in N,N-dimethylformamide (1.0 ml), and then diisopropylethylamine (0.105 ml, 0.603 mmol), N-hydroxysuccinimide (38 mg, 0.333 mmol), and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (64 mg, 0.335 mmol) were added thereto. The mixture was stirred at room temperature for 5.5 hours, and then an N,N-dimethylformamide (2.0 ml) solution of (3-aminomethyloxetan-3-ylmethyl)tritylamine (160 mg, 0.446 mmol) obtained in Step 1 above was added thereto. The prepared reaction solution was stirred at room temperature for 17 hours. A saturated aqueous sodium chloride solution (20 mL) was added to the reaction solution, and extracted three times with ethyl acetate (20 ml). The extract was sequentially washed three times with a saturated aqueous sodium bicarbonate solution (30 ml) and then three times with a saturated aqueous sodium chloride solution (30 ml). The washed ethyl acetate solution was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (developing solvent: dichloromethane:methanol=30:1) to yield 5-(2-amino-6-chloropyrimidin-4-yl)-2,4-dimethyl-N-{3-[(tritylamino)methyl]oxetan-3-ylmethyl}benzamide (169 mg) as a white solid material.

1. concentrationconcentrated under reduced pressure
2. dissolutionThe resulting white solid material was dissolved in N,N-dimethylformamide (1.0 ml)
3. stirringThe mixture was stirred at room temperature for 5.5 hours
4. customThe prepared reaction solution
5. stirringwas stirred at room temperature for 17 hours
6. extractionextracted three times with ethyl acetate (20 ml)
7. washThe extract was sequentially washed three times with a saturated aqueous sodium bicarbonate solution (30 ml)
8. dry with materialThe washed ethyl acetate solution was dried over anhydrous sodium sulfate
9. filtrationAfter filtration
10. concentrationthe filtrate was concentrated under reduced pressure
11. customThe resulting crude product was purified by silica gel column chromatography (developing solvent: dichloromethane:methanol=30:1)