Dimethylformamide → 9-Chloro-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepine-2-carbaldehyde

HRID 1629422Notes

Reaction equation

HRID 1629422 reaction equation
C([Mg]Br)C.[Cl:5][C:6]1[N:20]=[CH:19][C:9]2[C:10]3[N:11]([CH:15]=[C:16](I)[N:17]=3)[CH2:12][CH2:13][O:14][C:8]=2[CH:7]=1.CN(C)[CH:23]=[O:24]>O1CCCC1>[Cl:5][C:6]1[N:20]=[CH:19][C:9]2[C:10]3[N:11]([CH:15]=[C:16]([CH:23]=[O:24])[N:17]=3)[CH2:12][CH2:13][O:14][C:8]=2[CH:7]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 582047809-Chloro-2-iodo-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepineHCID 178418443HCID 178418443, compound

Product 1

HCID 582044299-Chloro-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepine-2-carbaldehydeYield 98.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Ethylmagnesium bromide (3.0 M in Et2O, 100 mmol, 33.3 mL) was added dropwise to a solution of 9-chloro-2-iodo-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepine (10.0 g, 28.8 mmol) in tetrahydrofuran (173 mL) at −20° C. The mixture was maintained at this temperature 20 min and then allowed to warm to ambient temperature for a 1 hr period. At this point, the reaction was re-cooled to −20° C. and N,N-dimethylformamide (8.9 mL, 115 mmol) was added to the mixture. Stirring was continued for 16 h before quenching with saturated aqueous ammonium chloride solution (220 mL) and further dilution with EtOAc (250 mL). The phases were separated and the aqueous layer was extracted twice with EtOAc. The combined organic portions were washed once with brine, dried over MgSO4, filtered and concentrated in vacuo. This provided 7.08 g (98% yield) of 9-chloro-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepine-2-carbaldehyde as a yellow solid in >95% purity as determined by analytical HPLC. MS (ESI+): m/z 249.8 (M+H+), calc. 249.65

Workup

  1. temperatureThe mixture was maintained at this temperature 20 min
  2. temperatureAt this point, the reaction was re-cooled to −20° C.
  3. custombefore quenching with saturated aqueous ammonium chloride solution (220 mL) and further dilution with EtOAc (250 mL)
  4. customThe phases were separated
  5. extractionthe aqueous layer was extracted twice with EtOAc
  6. washThe combined organic portions were washed once with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-290be337f3834795908892d264405c07
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

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