Azobisisobutyronitrile → 3-(2-(4-fluorophenyl)-3-formylfuro[2,3-b]pyridin-5-yl)-N-(2-phenylpropan-2-yl)benzamide

HRID 44071Notes

Reaction equation

HRID 44071 reaction equation
CC(N=NC(C#N)(C)C)(C#N)C.C1C(=O)N(Br)C(=[O:16])C1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[O:54][C:31]3=[N:32][CH:33]=[C:34]([C:36]4[CH:37]=[C:38]([CH:51]=[CH:52][CH:53]=4)[C:39]([NH:41][C:42]([C:45]4[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=4)([CH3:44])[CH3:43])=[O:40])[CH:35]=[C:30]3[C:29]=2[CH3:55])=[CH:24][CH:23]=1.C[N+]1([O-])CCOCC1>C(Cl)(Cl)(Cl)Cl>[F:21][C:22]1[CH:23]=[CH:24][C:25]([C:28]2[O:54][C:31]3=[N:32][CH:33]=[C:34]([C:36]4[CH:37]=[C:38]([CH:51]=[CH:52][CH:53]=4)[C:39]([NH:41][C:42]([C:45]4[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=4)([CH3:44])[CH3:43])=[O:40])[CH:35]=[C:30]3[C:29]=2[CH:55]=[O:16])=[CH:26][CH:27]=1

Participants

6

Reactant 4

HCID 6547AzobisisobutyronitrileHCID 67184N-bromobutanimideHCID 82029Methyl morpholine oxideHCID 59233729HCID 59233729, compound

Product 1

HCID 592338023-(2-(4-fluorophenyl)-3-formylfuro[2,3-b]pyridin-5-yl)-N-(2-phenylpropan-2-yl)benzamideYield 66.7%

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Conditions

Temperature
76 °C

Procedure

AIBN (1.0 mg, 6.1 μmol) was added to a stirring solution of NBS (4.6 mg, 0.026 mmol) and 3-(2-(4-fluorophenyl)-3-methylfuro[2,3-b]pyridin-5-yl)-N-(2-phenylpropan-2-yl)benzamide (11 mg, 0.024 mmol) in CCl4 (1 mL). The mixture was heated to 76° C. and allowed to stir for 2 hours. The reaction was concentrated and diluted with DMSO (1 mL) and treated with NMO (3.4 mg, 0.028 mmol) and subjected to microwave irradiation (150° C.) for 5 min. The reaction was purified by preparative reverse phase HPLC on a C18 column using a suitably buffered H2O/CH3CN gradient, and concentrated to give to give the expected product 3-(2-(4-fluorophenyl)-3-formylfuro[2,3-b]pyridin-5-yl)-N-(2-phenylpropan-2-yl)benzamide (7.5 mg, 0.016 mmol, 66% yield) consistent by LCMS and NMR. 1H NMR (500 MHz, DMSO-d6) δ ppm 10.31 (1H, s), 8.84 (1H, s), 8.79 (1H, s), 8.65 (1H, s), 8.19-8.26 (3H, m), 7.89-7.97 (2H, m), 7.59-7.67 (1H, m), 7.54 (2 H, t, J=8.55 Hz), 7.42 (2H, d, J=7.93 Hz), 7.30 (2H, t, J=7.63 Hz), 7.13-7.23 (1H, m), 1.71 (6H, s). LC-MS retention time: 1.75 min; m/z (MH+): 479. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters XBridge 5u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode.

Workup

  1. concentrationThe reaction was concentrated
  2. additiondiluted with DMSO (1 mL)
  3. customsubjected to microwave irradiation (150° C.) for 5 min
  4. customThe reaction was purified by preparative reverse phase HPLC on a C18 column
  5. concentrationconcentrated
  6. customto give

Sources & evidence

ORD record
ord-a57b1e64f52343b2981cd386bc583f6c
Source dataset
uspto-grants-2013_09
Patent number
US08536338B2

Reaction notes

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