Reaction #1702136

Reaction equation

{3-[(5-chloro-4-{[3-(3-methoxyphenyl)propyl]amino}pyrimidin-2-yl)amino]phenyl}methanol

boron tribromide

water

→

desired product

Yield 75.0%

3-{3-[(2-{[3-(Bromomethyl)phenyl]amino}-5-chloropyrimidin-4-yl)amino]propyl}phenol

Yield 75.0%

Solvents

methylene chloride

methylene chloride

Conditions

Workup

1. 1
   workup.ADDITIONwas added
2. 2
   Temperatureto warm up to rt
3. 3
   OtherAfter methylene chloride layer was separated
4. 4
   workup.ADDITIONwater and EtOAc were added
5. 5
   ExtractionThe aqueous layer was extracted with EtOAc twice
6. 6
   DryingThe combined organic layers were dried over Na2SO4
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated (
9. 9
   Otherthen triturated with cold EtOAc)

Procedure

To a solution of {3-[(5-chloro-4-{[3-(3-methoxyphenyl)propyl]amino}pyrimidin-2-yl)amino]phenyl}methanol (0.30 g, 0.75 mmol) in methylene chloride (4.8 mL) was added slowly a solution of boron tribromide in methylene chloride (3.8 mL, 1.0 M) at 0° C. The mixture was allowed to warm up to rt and stirred overnight. The resultant mixture was cooled in a dry ice bath when water was added. The mixture was allowed to warm up to rt. After methylene chloride layer was separated, water and EtOAc were added. The aqueous layer was extracted with EtOAc twice. The combined organic layers were dried over Na2SO4, filtered, and concentrated (then triturated with cold EtOAc) to give the desired product as an off-white powder (252 mg, 75%). LCMS for C20H21BrClN4O (M+H)+: m/z=447.0, 449.0. 1H NMR (400 MHz, CD3OD): δ 7.92 (s, 1H), 7.63 (s, 1H), 7.39 (s, 1H), 7.38 (m, 2H), 7.03 (t, J=7.2 Hz, 1H), 6.61 (m, 2H), 6.58 (s, 1H), 4.56 (s, 2H), 3.60 (t, J=7.6 Hz, 2H), 2.58 (t, J=7.6 Hz, 2H), 1.96 (m, 2H).

Source