Water → (4-fluoro-3-hydroxyphenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone

HRID 1424482Notes

Reaction equation

HRID 1424482 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[N:19]=[C:18]([NH:20][C:21]3[CH:25]=[C:24]([CH3:26])[NH:23][N:22]=3)[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)=[O:9])=[CH:4][C:3]=1[O:27]C.B(Br)(Br)Br.C(Cl)Cl.O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[N:19]=[C:18]([NH:20][C:21]3[CH:25]=[C:24]([CH3:26])[NH:23][N:22]=3)[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)=[O:9])=[CH:4][C:3]=1[OH:27]

Participants

5

Reactant 3

HCID 962WaterHCID 22277759Boron tribromide dichloromethane2×HCID 56848550(4-fluoro-3-methoxyphenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone

Product 1

HCID 46893655(4-fluoro-3-hydroxyphenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanoneYield 21%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred suspension of (4-fluoro-3-methoxyphenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone from Example 76 (100 mg, 0.265 mmol) in DCM (4 mL) at 0° C., was added dropwise 1.0 M boron tribromide/DCM (2.12 mL, 2.12 mmol). The mixture was stirred at 0° C. for 30 min. Additional 1.0 M boron tribromide/DCM (1.50 mL, 1.50 mmol) was added and the mixture was allowed to warm to rt and stir for a further 2.5 h. Water (10 mL) was added, and the mixture was extracted with 25% 2-propanol/DCM (2×). T The combined organic layers were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was triturated with diethyl ether and the resulting solid was collected by filtration and dried. The solid was further purified by reverse-phase HPLC eluting with a mixture of water and acetonitrile to afford (4-fluoro-3-hydroxyphenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone as a yellow solid (20 mg, 21%). 1H NMR (300 MHz, DMSO-d6) δ ppm 2.19 (s, 3H), 6.51 (s, 1H), 7.28 (dd, J=10.8, 8.4 Hz, 1H), 7.39 (m, 1H), 7.58 (dd, J=8.7, 1.8 Hz, 1H), 7.67 (ddd, J=8.1, 8.1, 1.5 Hz, 1H), 7.83-7.92 (m, 2H), 8.73 (d, J=8.4 Hz, 1H), 10.65 (br s, 1H), 12.22 (br s, 1H); LC-MS (ESI) m/z 364 (M+H)+.

Workup

  1. temperatureto warm to rt
  2. stirringstir for a further 2.5 h
  3. extractionthe mixture was extracted with 25% 2-propanol/DCM (2×)
  4. dry with materialT The combined organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was triturated with diethyl ether
  8. filtrationthe resulting solid was collected by filtration
  9. customdried
  10. customThe solid was further purified by reverse-phase HPLC
  11. washeluting with a mixture of water and acetonitrile

Sources & evidence

ORD record
ord-1413815a375546de81d0c7661ffeb736
Source dataset
uspto-grants-2015_01
Patent number
US08927711B2

Reaction notes

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