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

HRID 1614932Notes

Reaction equation

HRID 1614932 reaction equation
[Cl:1][C:2]1[C:3]([NH:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26]C)[CH:21]=2)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[C:11]([CH2:15][CH2:16]O)[CH:12]=[CH:13][CH:14]=2)=[N:6][CH:7]=1.ClCCl.B(Br)(Br)[Br:32].O>CCOC(C)=O>[Br:32][CH2:16][CH2:15][C:11]1[CH:10]=[C:9]([NH:8][C:5]2[N:4]=[C:3]([NH:18][CH2:19][C:20]3[CH:21]=[C:22]([OH:26])[CH:23]=[CH:24][CH:25]=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 584679152-[3-({5-Chloro-4-[(3-methoxybenzyl)amino]pyrimidin-2-yl}amino)phenyl]ethanol

Product 1

HCID 584678993-{[(2-{[3-(2-Bromoethyl)phenyl]amino}-5-chloropyrimidin-4-yl)amino]methyl}phenolYield 20%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Into a 1-neck round-bottom flask were added 2-[3-({5-chloro-4-[(3-methoxybenzyl)amino]pyrimidin-2-yl}amino)phenyl]ethanol (0.20 g, 0.52 mmol) and dichloromethane (“DCM”, 5 mL). To the reaction mixture was added a solution of boron tribromide in methylene chloride (1.6 mL, 1.6 mmol, 1.0 M) at 0° C. The resulting mixture was allowed to warm up to rt and stirred overnight. The resulted mixture was cooled in a dry ice bath when water (10 mL) was added. The mixture was allowed to warm up to rt and EtOAc was added. The aqueous layer was extracted with EtOAc twice. The organic layers were combined and concentrated under vacuum. The crude product was purified by silica gel column chromatography to give the desired product as a light brown powder (34 mg, 20%). LCMS for C19H19BrClN4O (M+H)+: m/z=371.1, 373.1. 1H NMR (400 MHz, DMSO-d6): δ 9.30 (s, 1H), 9.11 (s, 1H), 7.95 (s, 1H), 7.74 (t, J=6.1 Hz, 1H), 7.42 (m, 1H), 7.08 (t, J=7.9 Hz, 1H), 7.03 (dd, J=8.7, 7.6 Hz, 1H), 6.71 (dd, J=11.5, 7.6 Hz, 1H), 6.69 (s, 1H), 6.58 (dd, J=8.0, 2.3 Hz, 1H), 4.56 (m, 2H), 3.50 (m, 2H), 2.56 (t, J=7.1 Hz, 2H).

Workup

  1. additionwas added
  2. temperatureto warm up to rt
  3. extractionThe aqueous layer was extracted with EtOAc twice
  4. concentrationconcentrated under vacuum
  5. customThe crude product was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-135f6381a168424b9dd6539a1db09d15
Source dataset
uspto-grants-2014_07
Patent number
US08765727B2

Reaction notes

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