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

HRID 1614929Notes

Reaction equation

HRID 1614929 reaction equation
[Cl:1][C:2]1[C:3]([NH:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([O:25]C)[CH:20]=2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[C:11]([CH2:15]O)[CH:12]=[CH:13][CH:14]=2)=[N:6][CH:7]=1.C(Cl)Cl.B(Br)(Br)[Br:31].O>CCOC(C)=O>[Br:31][CH2:15][C:11]1[CH:10]=[C:9]([NH:8][C:5]2[N:4]=[C:3]([NH:17][CH2:18][C:19]3[CH:20]=[C:21]([OH:25])[CH:22]=[CH:23][CH:24]=3)[C:2]([Cl:1])=[CH:7][N:6]=2)[CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6344Dichloromethane2×HCID 25134Boron tribromideHCID 58467863[3-({5-Chloro-4-[(3-methoxybenzyl)amino]pyrimidin-2-yl}amino)phenyl]methanol

Product 1

HCID 584678713-{[(2-{[3-(Bromomethyl)phenyl]amino}-5-chloropyrimidin-4-yl)amino]methyl}phenolYield 99%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

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).

Workup

  1. additionwas added
  2. temperatureto warm up to rt
  3. extractionThe aqueous layer was extracted with EtOAc twice
  4. customsolvent removed under vacuum
  5. customThe crude was purified by prep-HPLC

Sources & evidence

ORD record
ord-33d720bb089c4f3ab6bc572cd2e4be50
Source dataset
uspto-grants-2014_07
Patent number
US08765727B2

Reaction notes

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