Methylamine → Methyl 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate

HRID 44081Notes

Reaction equation

HRID 44081 reaction equation
CC(N=NC(C#N)(C)C)([C:4]#[N:5])C.C1C(=O)N(Br)C(=O)C1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[O:46][C:31]3=[N:32][CH:33]=[C:34]([C:36]4[CH:37]=[C:38]([CH:43]=[CH:44][CH:45]=4)[C:39]([O:41][CH3:42])=[O:40])[CH:35]=[C:30]3[C:29]=2[CH:47]=[O:48])=[CH:24][CH:23]=1.CN>C(Cl)(Cl)(Cl)Cl.CO>[F:21][C:22]1[CH:23]=[CH:24][C:25]([C:28]2[O:46][C:31]3=[N:32][CH:33]=[C:34]([C:36]4[CH:37]=[C:38]([CH:43]=[CH:44][CH:45]=4)[C:39]([O:41][CH3:42])=[O:40])[CH:35]=[C:30]3[C:29]=2[C:47](=[O:48])[NH:5][CH3:4])=[CH:26][CH:27]=1

Participants

7

Reactant 4

HCID 6329MethylamineHCID 6547AzobisisobutyronitrileHCID 67184N-bromobutanimideHCID 86639962Methyl 3-(2-(4-fluorophenyl)-3-formylfuro[2,3-b]pyridin-5-yl)benzoate

Product 1

HCID 67217484Methyl 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoateYield 210.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 5943Carbon TetrachlorideSolvent

Procedure

AIBN (4.6 mg, 0.028 mmol) and NBS (21.6 mg, 0.121 mmol) was added to a stirring solution of methyl 3-(2-(4-fluorophenyl)-3-formylfuro[2,3-b]pyridin-5-yl)benzoate (35 mg, 0.093 mmol) in CCl4 (5 mL) at 95° C. It was allowed to stir for 30 min and then allowed to cool and was then treated with methanamine (0.466 mL, 0.932 mmol, 2M in THF) and the reaction was allowed to stir for 10 min then diluted with MeOH. A ppt formed which was filtered away and the filtrate was concentrated and was purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=320 nm) to give to give the expected product methyl 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoate (24 mg, 0.059 mmol, 64% yield) consistent by LCMS and NMR. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.60 (1H, d, J=2.14 Hz), 8.44 (1H, d, J=2.44 Hz), 8.32 (1H, s), 8.10 (1H, d, J=7.93 Hz), 7.95-8.00 (2H, m), 7.84 (1H, d, J=7.63 Hz), 7.59 (1H, t, J=7.78 Hz), 7.22-7.26 (2H, m), 5.91 (1H, br. s.), 3.98 (3H, s), 3.03 (3H, d, J=4.88 Hz). LC-MS retention time: 1.46 min; m/z (MH+): 405. 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. temperatureto cool
  2. stirringto stir for 10 min
  3. customA ppt formed which
  4. filtrationwas filtered away
  5. concentrationthe filtrate was concentrated
  6. customwas purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=320 nm)
  7. customto give

Sources & evidence

ORD record
ord-cba24a4c21f54d5db96cc3cd165dcf7f
Source dataset
uspto-grants-2013_09
Patent number
US08536338B2

Reaction notes

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