Boron tribromide → HCID 178424336, compound

HRID 341094Notes

Reaction equation

HRID 341094 reaction equation
C[O:2][C:3]1[C:4]2[C:5]3[C:6]([C:25](=[O:35])[N:26]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[CH3:34])[N:27]=3)=[CH:7][N:8]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([N:20]4[CH:24]=[CH:23][CH:22]=[N:21]4)=[CH:16][CH:15]=3)[C:9]=2[CH:10]=[CH:11][CH:12]=1.B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>ClCCl>[OH:2][C:3]1[C:4]2[C:5]3[C:6]([C:25](=[O:35])[N:26]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=4[CH3:34])[N:27]=3)=[CH:7][N:8]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([N:20]4[CH:24]=[CH:23][CH:22]=[N:21]4)=[CH:16][CH:15]=3)[C:9]=2[CH:10]=[CH:11][CH:12]=1

Participants

5

Reactant 3

HCID 25134Boron tribromide2×HCID 516892Sodium Bicarbonate2×HCID 69935077HCID 69935077, compound

Product 1

HCID 178424336HCID 178424336, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

9-(Methyloxy)-2-(2-methylphenyl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 723, 37 mg, 0.80 mmol) was dissolved in dichloromethane (5 mL) and cooled to −78° C. Boron tribromide (0.24 mL, 1 M dichloromethane solution, 0.24 mmol, 3 equiv) was added and the mixture was stirred for 3 hours at −78° C. The mixture was then warmed to −40° C. and stirred for an additional 30 minutes. The acetonitrile/dry ice bath was removed, the mixture was warmed to ambient temperature and stirred for 30 minutes. Additional boron tribromide (0.24 mL, 1 M dichloromethane solution, 0.24 mmol, 3 equiv) was added and the mixture was stirred for an additional 45 minutes at ambient temperature. The mixture was treated with sodium bicarbonate (6 mL, aqueous saturated) slowly over 5 minutes, stirred for 30 minutes at ambient temperature and then poured into sodium bicarbonate (50 mL, aqueous saturated). The aqueous layer was extracted with dichloromethane (3×100 mL) and the combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatograph (100:0 to 90:10 dichloromethane:methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 9.71 (1H, s), 8.51 (1H, s), 7.91 (1H, d, J=1.9 Hz), 7.74-7.72 (3H, m), 7.47-7.45 (1H, m), 7.39 (1H, t, J=8.5 Hz), 7.36-7.30 (5H, m), 7.01 (1H, d, J=8.3 Hz), 6.94 (1H, d, J=8.6 Hz), 6.48 (1H, m), 5.46 (2H, s), 2.35 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 448.1785 [(M+H)+; calculated for C27H22N5O2: 448.1768].

Workup

  1. temperatureThe mixture was then warmed to −40° C.
  2. stirringstirred for an additional 30 minutes
  3. customThe acetonitrile/dry ice bath was removed
  4. temperaturethe mixture was warmed to ambient temperature
  5. stirringstirred for 30 minutes
  6. stirringthe mixture was stirred for an additional 45 minutes at ambient temperature
  7. stirringstirred for 30 minutes at ambient temperature
  8. extractionThe aqueous layer was extracted with dichloromethane (3×100 mL)
  9. dry with materialthe combined organic extracts were dried with sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by silica gel gradient chromatograph (100:0 to 90:10 dichloromethane:methanol)

Sources & evidence

ORD record
ord-8580459a911c4b899a3ac1d6b817731d
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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