Reaction #1810847

Reaction equation

acetone

n-butyl lithium

4-(1-Cyclopropylmethyl-2-methylimidazol-5-yl)-2-{4-[N-(2-methoxyethyl)-N-(t-butyl)sulphamoyl]anilino}pyrimidine

water

→

title compound

Yield 36.2%

4-(1-Cyclopropylmethyl-2-(2-hydroxy-2-methylpropyl)imidazol-5-yl)-2-{4-[N-(2-methoxyethyl)-N-(t-butyl)sulphamoyl]anilino}pyrimidine

Yield 36.2%

Solvents

—

hexanes

THF

Conditions

Workup

1. 1
   Temperaturemaintaining the temperature at less than −65° C
2. 2
   Temperatureto warm to ambient temperature
3. 3
   workup.STIRRINGstirred for 1 hour
4. 4
   Extractionextracted with EtOAc (2×50 ml)
5. 5
   Washwashed with water (50 ml), brine (50 ml)
6. 6
   Otherdried
7. 7
   OtherThe volatiles were removed
8. 8
   Otherthe residue was purified by chromatography on silica gel eluting with EtOAc

Procedure

4-(1-Cyclopropylmethyl-2-methylimidazol-5-yl)-2-{4-[N-(2-methoxyethyl)-N-(t-butyl)sulphamoyl]anilino}pyrimidine (Method 78; 1.15 g, 2.31 mmol) was dissolved in anhydrous THF (80 ml), under nitrogen. The solution was cooled to −78° C. and n-butyl lithium (2.88 ml of a 1.6 N solution in hexanes, 4.62 mmol), was added slowly, maintaining the temperature at less than −65° C. The reaction mixture was then stirred at −78° C. for 30 minutes, then acetone (1187 μl, 2.54 mmol) was added and mixture allowed to warm to ambient temperature and stirred for 1 hour. The reaction mixture was then poured into water (100 ml), and extracted with EtOAc (2×50 ml). The organic extracts were combined, washed with water (50 ml), brine (50 ml), and dried. The volatiles were removed and the residue was purified by chromatography on silica gel eluting with EtOAc to give the title compound (465 mg, 36%) as a yellow solid. NMR: 0.10 (m, 2H) 0.18 (m, 2H) 0.89 (m, H) 1.07 (s, 6H) 1.12 (s, 9H) 2.75 (s, 2H) 3.15 (s, 3H) 3.38 (m, 4H) 4.54 (d, 2H) 7.11 (d, H) 7.58 (m, 3H) 7.75 (d, 2H) 8.34 (d, H) 9.8 (s, H); m/z 557.

Source