반응 #73413

반응 방정식

5-{6-[(4-Bromo-butyrylamino)-methyl]-pyrimidin-4-yloxy}-indole-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide

Sodium hydride

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title compound

5-[6-(2-Oxo-pyrrolidin-1-ylmethyl)-pyrimidin-4-yloxy]-indole-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide

용매

THF

반응 조건

후처리

1. 1
   온도to warm to room temperature overnight
2. 2
   기타The reaction is quenched with water
3. 3
   workup.ADDITIONdiluted with ethyl acetate
4. 4
   기타The organic layer is removed
5. 5
   기타dried
6. 6
   농축concentrated
7. 7
   기타the residue is separated via semi-prep HPLC (C18; 20-100% I/H2O with 0.1% TFA)

실험 절차

5-{6-[(4-Bromo-butyrylamino)-methyl]-pyrimidin-4-yloxy}-indole-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide (0.353 g, 0.595 mmol) is dissolved in 10 mL THF and cooled to 0° C. Sodium hydride (63 mg, 1.5 mmol, 60% in mineral oil) is added and the reaction is allowed to warm to room temperature overnight. The reaction is quenched with water and diluted with ethyl acetate. The organic layer is removed, dried, and concentrated and the residue is separated via semi-prep HPLC (C18; 20-100% I/H2O with 0.1% TFA) to provide the title compound. MS (ESI) m/z 514.9 (M+1); 1H NMR (400 m/z, DMSO-d6) δ ppm 10.40 (s, 1 H), 8.68 (d, J=1.01 Hz, 1 H), 8.28 (d, J=9.09 Hz, 1 H), 8.09-8.12 (m, 2 H), 7.99-8.03 (m, 1 H), 7.57 (t, J=9.85 Hz, 1 H), 7.49 (d, J=2.27 Hz, 1 H), 7.15 (dd, J=8.97, 2.40 Hz, 1 H), 6.94 (d, J=1.01 Hz, 1 H), 6.81 (d, J=3.79 Hz, 1 H), 4.45 (s, 2 H), 3.42 (t, J=6.95 Hz, 2 H), 2.29-2.34 (m, 3 H), 2.00 (t, J=7.58 Hz, 2 H).

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