| 58% |
|
[0258] To 4-bromo-1H-pyrrolo[2,3-b]pyridine (2.00 g), the compound of Reference Example 1(2a) (4.60 g) and tripotassiumphosphate (5.41 g), 1,4-dioxane (20 mL) and water (3.3 mL) were added, followed by nitrogen substitution, andPdCl2(dppf)CH2Cl2 (746 mg) was then added to the reaction mixture. Thus obtained mixture was stirred at 100C for 5hours. Thereafter, the reaction mixture was cooled to a room temperature, and ethyl acetate and water were then addedto the mixture. Thereafter, thus obtained mixture was filtered through Celite. The filtrate was then extracted with ethylacetate, and the gathered organic layer was then washed with water and then with a saturated saline. The resultant wasdried over anhydrous sodium sulfate, and then concentrated under a reduced pressure. The obtained residue waspurified by silica gel chromatography (chloroform : methanol) to obtain a corresponding coupling product. The obtainedcoupling product was subjected to the subsequent reaction without further purification.[0259] DMF (30 mL) was added to the obtained coupling product, and the obtained mixture was then cooled to 0C.Subsequently, N-iodosuccinimide (2.52 g) was added to the mixture, and the obtained mixture was then stirred at 0Cfor 30 minutes. Thereafter, a 0.5 M aqueous solution of sodium hydrogen sulfite was added to the reaction mixture, andthe obtained mixture was then extracted with ethyl acetate. The gathered organic layer was washed with water and thenwith a saturated saline. The resultant was dried over anhydrous sodium sulfate, and then concentrated under a reducedpressure. The obtained residue was purified by silica gel chromatography (chloroform : methanol) to obtain a correspondingiodine product. The obtained iodine product was subjected to the subsequent reaction without further purification.[0260] DMF (30 mL) was added to the obtained iodine product, and the obtained mixture was then cooled to 0C.Thereafter, 60% sodium hydride (1.02 g), and then, para-toluenesulfonyl chloride (2.33 g) were added to the reactionmixture, and the obtained mixture was then stirred at 0C for 30 minutes. Thereafter, ice water was added to the reactionmixture, and the water layer was then extracted with ethyl acetate. The gathered organic layer was washed with waterand then with a saturated saline. The resultant was dried over anhydrous sodium sulfate, and then concentrated undera reduced pressure. The obtained residue was purified by silica gel chromatography (hexane : ethyl acetate) to obtaina product of interest (3.49 g, yield: 58%).1H NMR (CDCl3) delta: 8.35 (d, J=4.9 Hz, 1H), 8.10 (d, J=8.5 Hz, 2H), 7.89 (s, 1H), 7.30 (d, J=8.5 Hz, 2H), 6.94 (d, J=4.9Hz, 1H), 5.72 - 5.67 (m, 1H), 4.75 - 4.59(m, 1H), 4.11 - 3.97 (m, 1H), 2.70 - 2.60 (m, 1H), 2.40 - 2.32 (m, 2H), 2.39 (s,3H), 2.22 - 2.09 (m, 1H), 2.04 - 1.94 (m, 1H), 1.75 - 1.62 (m, 1H), 1.44 (s, 9H)ESI-MS m/z 594(MH+) |
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