Water → 2-Bromo-1-(2-(1-phenylcyclopropyl)quinazolin-8-yl)ethanone

HRID 1056074Notes

Reaction equation

HRID 1056074 reaction equation
C1C(=O)N([Br:8])C(=O)C1.C([O:13][C:14]([C:16]1[CH:17]=[CH:18][CH:19]=[C:20]2[C:25]=1[N:24]=[C:23]([C:26]1([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:28][CH2:27]1)[N:22]=[CH:21]2)=[CH2:15])CCC.O>C1COCC1>[Br:8][CH2:13][C:14]([C:16]1[CH:17]=[CH:18][CH:19]=[C:20]2[C:25]=1[N:24]=[C:23]([C:26]1([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH2:28][CH2:27]1)[N:22]=[CH:21]2)=[O:15]

Participants

5

Reactant 3

HCID 962WaterHCID 67184N-bromobutanimideHCID 897819738-(1-Butoxyvinyl)-2-(1-phenylcyclopropyl)quinazoline

Product 1

HCID 897819522-Bromo-1-(2-(1-phenylcyclopropyl)quinazolin-8-yl)ethanoneYield 117.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

NBS (51.7 mg, 0.290 mmol) was added to a solution 8-(1-butoxyvinyl)-2-(1-phenylcyclopropyl)quinazoline (100.0 mg, 0.290 mmol) in THF (2.2 mL) and water (0.084 mL, 4.65 mmol) at 0° C. and the resulting solution was stirred at 0° C. for 2 min. The mixture was partitioned between Et2O (50 mL) and water (30 mL). The organic layer was separated, sequentially washed with saturated aq. NaHCO3 (20 mL), water (20 mL), and brine (20 mL), dried over Na2SO4, filtered, and concentrated in vacuo to provide crude 2-bromo-1-(2-(1-phenylcyclopropyl)quinazolin-8-yl)ethanone (124.8 mg) as a light-yellow oil. NH4OAc (90 mg, 1.161 mmol) and piperidine-2,4-dione (39.4 mg, 0.348 mmol) were added to the resulting oil, and the mixture was taken up in EtOH (2.2 mL) and stirred under argon in a sealed flask at 50° C. for 15.5 h. The reaction was cooled to 25° C. and concentrated in vacuo. The residue was partitioned between DCM (50 mL) and saturated aq. NaHCO3 (30 mL). The aq. layer was extracted with DCM (2×30 mL), and the combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-10% MeOH/DCM) furnished 2-(2-(1-phenylcyclopropyl)quinazolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (35.3 mg, 0.093 mmol, 32% yield) as a yellow-orange solid: 1H NMR (400 MHz, CDCl3) δ ppm 11.24 (1H, br. s.), 9.28 (1H, s), 8.16 (1H, d, J=7.6 Hz), 7.66 (1H, d, J=7.8 Hz), 7.52-7.58 (3H, m), 7.46 (2H, t, J=7.3 Hz), 7.39 (1H, t, J=7.2 Hz), 7.11 (1H, d, J=2.2 Hz), 5.45 (1H, br. s.), 3.51 (2H, td, J=7.0, 2.1 Hz), 2.49 (2H, t, J=6.9 Hz), 1.95 (2H, q, J=3.6 Hz), 1.51 (2H, q, J=3.6 Hz). m/z (ESI, +ve) 381.2 (M+H)+.

Workup

  1. customThe mixture was partitioned between Et2O (50 mL) and water (30 mL)
  2. customThe organic layer was separated
  3. washsequentially washed with saturated aq. NaHCO3 (20 mL), water (20 mL), and brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-803650d9e0294e27a87426b6fdadd841
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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