反应详情

To a suspension of N-(4-chlorobenzyl)-4-hydroxy-2-iodothieno[2,3-b]pyridine-5-carboxamide (Example No. 2) (1.00 g) in diethylamine (28 mL) is added copper iodide (0.128 g) and Pd(PPh3)2Cl2 (0.032 g) followed by addition of propargyl alcohol (0.16 mL). The reaction is stirred at rt for 3 d. The reaction mixture is partitioned between H2O (100 mL) and ethyl acetate (100 mL). The organic layer is removed, and the aqueous layer is extracted with ethyl acetate (2×100 mL). Combined organic layers are washed with a saturated aqueous NH4Cl solution, dried with MgSO4, filtered, and concentrated in vacuo. The resulting orange solid is purified via column chromatography (CH2Cl2:CH3OH; 98:2, 95:5). Fractions homogeneous by TLC are combined and concentrated in vacuo to yield a pale orange solid which is recrystallized from CH2Cl2/CH3OH to yield 0.165 g (20%) of the title compound as an off-white solid.

1. customThe reaction mixture is partitioned between H2O (100 mL) and ethyl acetate (100 mL)
2. customThe organic layer is removed
3. extractionthe aqueous layer is extracted with ethyl acetate (2×100 mL)
4. washCombined organic layers are washed with a saturated aqueous NH4Cl solution
5. dry with materialdried with MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe resulting orange solid is purified via column chromatography (CH2Cl2:CH3OH; 98:2, 95:5)
9. concentrationconcentrated in vacuo
10. customto yield a pale orange solid which
11. customis recrystallized from CH2Cl2/CH3OH