Reaction #1702111

Reaction equation

water

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

methylene chloride

boron tribromide

methylene chloride

→

desired product

Yield 99.0%

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

Yield 99.0%

Solvents

EtOAc

Conditions

Workup

1. 1
   workup.ADDITIONwas added
2. 2
   Temperatureto warm up to rt
3. 3
   ExtractionThe aqueous layer was extracted with EtOAc twice
4. 4
   Othersolvent removed under vacuum
5. 5
   OtherThe crude was purified by prep-HPLC

Procedure

Into a 1-neck round-bottom flask were added [3-({5-chloro-4-[(3-methoxybenzyl)amino]pyrimidin-2-yl}amino)phenyl]methanol (0.66 g, 1.8 mmol) and 5 mL of methylene chloride. To the above mixture was slowly added a solution of boron tribromide in methylene chloride (2.7 mL, 2.7 mmol, 1.0 M) at 0° C. The mixture was allowed to warm up to room temperature (“rt”) and stirred overnight. The resultant mixture was cooled in a dry ice bath when water (10 mL) was added. The mixture was allowed to warm up to rt, followed by an addition of EtOAc. The aqueous layer was extracted with EtOAc twice. The organic layers were combined and solvent removed under vacuum. The crude was purified by prep-HPLC to give the desired product (730 mg, 99%). LCMS for C18H17BrClN4O (M+H)+: m/z=418.9, 420.9. 1H NMR (400 MHz, DMSO-d6): δ 9.55 (s, 1H), 9.34 (br s, 1H), 8.18 (s, 1H), 8.04 (s, 1H), 7.68 (t, J=1.7 Hz, 1H), 7.41 (m, 1H), 7.16 (t, J=7.9 Hz, 1H), 7.09 (t, J=7.9 Hz, 1H), 6.98 (d, J=7.7 Hz, 1H), 6.70 (m, 1H), 6.59 (m, 1H), 4.58 (d, J=6.6 Hz, 2H), 4.49 (s, 2H).

Source