Reaction #1702132

Reaction equation

NaHCO3

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

boron tribromide

BBr3

→

desired product

Yield 65.0%

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

Yield 65.0%

Solvents

methylene chloride

methylene chloride

Conditions

Workup

1. 1
   workup.STIRRINGthe reaction mixture was stirred at rt for one more day
2. 2
   OtherThe organic solvent was removed under vacuum and water/EtOAc
3. 3
   workup.ADDITIONwas added
4. 4
   ExtractionThe aqueous layer was extracted with EtOAc twice
5. 5
   DryingThe combined organic layers were dried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated (
8. 8
   Otherthen triturated with cold EtOAc)

Procedure

To a solution of 2-{3-[(5-chloro-4-{[2-(3-methoxyphenyl)ethyl]amino}pyrimidin-2-yl)amino]phenyl}ethanol (0.30 g, 0.75 mmol) in methylene chloride (4.8 mL) was added slowly a solution of boron tribromide in methylene chloride (2.2 mL, 2.2 mmol, 1.0 M) at 0° C. The mixture was allowed to warm up to rt and stirred overnight and the reaction was not complete. Thus additional 2 molar equivalents of BBr3 (1.5 mL, 1.5 mmol, 1.0M) were added, and the reaction mixture was stirred at rt for one more day and then the reaction was complete. To the mixture was added NaHCO3 (saturated aqueous solution). The organic solvent was removed under vacuum and water/EtOAc was 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 (222 mg, 65%). LCMS for C20H21BrClN4O (M+H)+: m/z=447.0, 449.0. 1H NMR (400 MHz, CD3OD): δ 7.92 (s, 1H), 7.37 (m, 3H), 7.20 (d, J=7.6 Hz, 1H), 7.04 (t, J=8.0 Hz, 1H), 6.58 (m, 3H), 3.74 (t, J=7.6 Hz, 2H), 3.61 (t, J=7.2 Hz, 2H), 3.14 (t, J=7.2 Hz, 2H), 2.83 (t, J=7.2 Hz, 2H).

Source