Boron tribromide → 4-[2-(5,8-Difluoroquinazolin-4-ylamino)-ethyl]-2-methylphenol

HRID 2386902Notes

Reaction equation

HRID 2386902 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:3]=1[C:4]([NH:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22]C)=[C:18]([CH3:24])[CH:17]=1)=[N:5][CH:6]=[N:7]2.B(Br)(Br)Br>C(Cl)Cl>[F:1][C:2]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:3]=1[C:4]([NH:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([CH3:24])[CH:17]=1)=[N:5][CH:6]=[N:7]2

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 59222937(5,8-Difluoroquinazolin-4-yl)-[2-(4-methoxy-3-methylphenyl)-ethyl]-amine

Product 1

HCID 592229364-[2-(5,8-Difluoroquinazolin-4-ylamino)-ethyl]-2-methylphenolYield 101.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (5,8-difluoroquinazolin-4-yl)-[2-(4-methoxy-3-methylphenyl)-ethyl]-amine (0.86 g, 2.6 mmol) in CH2Cl2 (10 mL) cooled to −50° C., was added 7.8 mL BBr3 (1 M in CH2Cl2, 7.8 mmol). The solution was allowed to warm to room temperature and stirred overnight, and then quenched slowly with methanol. The solvent was removed by rotary evaporation, and the residue was diluted with water and stirred for a few min. The pale yellow solid precipitate was collected by suction filtration, washed with water, and dried in vacuum at 50° C. overnight to give 0.83 g (quantitative yield) of 4-[2-(5,8-difluoroquinazolin-4-ylamino)-ethyl]-2-methylphenol. 1H NMR (d4-DMSO+d6-acetone): δ 9.5-8.5 (m, 3H), 7.97 (m, 1H), 7.61 (m, 1H), 6.99 (s, 1H), 6.91 (d, J=8.1 Hz, 1H), 6.75 (d, J=8.1 Hz, 1H), 3.92 (m, 2H), 2.88 (t, J=7.8 Hz, 2H), 2.11 (s, 3H). LC/MS: 316.04 (M++1). The product was used in the following reaction without further purification. M.P. 244-251° C.

Workup

  1. customquenched slowly with methanol
  2. customThe solvent was removed by rotary evaporation
  3. additionthe residue was diluted with water
  4. stirringstirred for a few min
  5. filtrationThe pale yellow solid precipitate was collected by suction filtration
  6. washwashed with water
  7. customdried in vacuum at 50° C. overnight

Sources & evidence

ORD record
ord-0976be45030145459fcf7d4db72742b8
Source dataset
uspto-grants-2012_09
Patent number
US08268843B2

Reaction notes

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