تفاعل #73406

معادلة التفاعل

sodium methanesulfinate

Methanesulfonyl chloride

4-fluoro-5-(2-hydroxymethyl-pyrimidin-4-yloxy)-2-methyl-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

Et3N

→

4-fluoro-5-(2-methanesulfonylmethyl-pyrimidin-4-yloxy)-2-methyl-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide

المذيبات

methanol

CH2Cl2

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe resulting mixture is warmed to and
2. 2
   تركيزThe mixture is concentrated
3. 3
   workup.STIRRINGThe resulting mixture is stirred at 23° C. for 24 h
4. 4
   أخرىpartitioned between EtOAc (40 mL) and water (40 mL)
5. 5
   استخلاصThe aqueous layer is extracted with EtOAc (2×40 mL)
6. 6
   غسيلThe combined organic layers are washed with brine (20 mL)
7. 7
   تجفيفdried (Na2SO4)
8. 8
   تركيزconcentrated
9. 9
   أخرىThe residue is purified by silica gel chromatography (0-100% EtOAc/heptane)

الإجراء التجريبي

Methanesulfonyl chloride (0.046 mL, 0.586 mmol) is added to a solution of 4-fluoro-5-(2-hydroxymethyl-pyrimidin-4-yloxy)-2-methyl-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide (180 mg, 0.391 mmol) and Et3N (0.109 mL, 0.782 mmol) in CH2Cl2 (5 mL) at 0° C. After 10 min, methanol is added, followed by sodium methanesulfinate (798 mg, 7.82 mmol). The resulting mixture is warmed to and stirred at 23° C. for 14 h. The mixture is concentrated and the residue is taken up in DMF (5 mL). The resulting mixture is stirred at 23° C. for 24 h, then partitioned between EtOAc (40 mL) and water (40 mL). The aqueous layer is extracted with EtOAc (2×40 mL). The combined organic layers are washed with brine (20 mL), dried (Na2SO4), and concentrated. The residue is purified by silica gel chromatography (0-100% EtOAc/heptane) to give 4-fluoro-5-(2-methanesulfonylmethyl-pyrimidin-4-yloxy)-2-methyl-indole-1-carboxylic acid (3-trifluoromethyl-phenyl)-amide. MS (ESI) m/z 474.0 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 10.98 (s, 1 H) 8.76 (d, J=5.81 Hz, 1 H)8.12 (s, 1 H)7.91 (d, J=8.34 Hz, 1 H)7.64-7.69 (m, 1 H)7.53 (d, J=8.84 Hz, 2 H)7.18-7.25 (m, 2 H)6.63 (s, 1 H)4.55 (s, 2 H)2.97 (s, 3 H)2.59 (s, 3 H)

المصدر