反应详情

To a solution of 1-{[5-(1-methyl-1H-indol-2-yl)-pyridin-3-ylamino]-methyl}-cyclobutanecarboxylic acid ethyl ester (Example 213b, 0.45 g, 1.21 mmol) in THF (150 mL) cooled with an ice-water bath is added iPrMgCl (2.0M in THF, 2.43 mL, 4.85 mmol) dropwise. After 45 min, the mixture is quenched with 1M aqueous NaHSO4 (5 mL), washed with saturated aqueous sodium bicarbonate and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue is purified by silica gel flash chromatography (heptane-ethyl acetate, 3:2 to 1:1), followed by purification by RP HPLC on an Xbridge RP18 eluting with a gradient of acetonitrile in 0.1% aqueous NH4OH to give 2-methyl-1-(1-{[5-(1-methyl-1H-indol-2-yl)-pyridin-3-ylamino]-methyl}-cyclobutyl)-propan-1-one.

1. customthe mixture is quenched with 1M aqueous NaHSO4 (5 mL)
2. washwashed with saturated aqueous sodium bicarbonate and brine
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue is purified by silica gel flash chromatography (heptane-ethyl acetate, 3:2 to 1:1)
7. customfollowed by purification by RP HPLC on an Xbridge
8. washRP18 eluting with a gradient of acetonitrile in 0.1% aqueous NH4OH