Cyclopropanecarboxaldehyde → HCID 59375392, compound

HRID 2192981Notes

Reaction equation

HRID 2192981 reaction equation
[Br:1][C:2]1[CH:24]=[CH:23][C:5]2[C:6]([NH:16][CH:17]([CH3:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[N:7][C:8]3[C:9](I)=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1.C1([Mg]Cl)C=CC=CC=1.C([Mg]Cl)(C)C.[CH:38]1([CH:41]=[O:42])[CH2:40][CH2:39]1>C1COCC1>[Br:1][C:2]1[CH:24]=[CH:23][C:5]2[C:6]([NH:16][CH:17]([CH3:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[N:7][C:8]3[C:9]([CH:41]([CH:38]4[CH2:40][CH2:39]4)[OH:42])=[CH:10][NH:11][C:12](=[O:14])[C:13]=3[C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 123114CyclopropanecarboxaldehydeHCID 59375664HCID 59375664, compoundHCID 178418918HCID 178418918, compoundHCID 178478979HCID 178478979, compound

Product 1

HCID 59375392HCID 59375392, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-30 °C

Procedure

9-bromo-4-iodo-6-[(1,2,2-trimethylpropyl)amino]benzo[c]-1,6-naphthyridin-1(2H)-one (50 mg, 0.100 mmol) was dissolved in THF and cooled to −30° C. Phenylmagnesium chloride (2M in THF) (105 μl, 0.210 mmol) was added dropwise, then stirred for 30 minutes before allowing to warm to room temperature by removing cooling baths and stirring an additional 30 minutes. Then, isopropylmagnesium chloride (2M in ether) (60.0 μl, 0.120 mmol) was added dropwise and stirred for 1 h. Then, cyclopropanecarboxaldehyde (29.9 μl, 0.400 mmol) was added and the reaction mixture was stirred for 30 minutes before quenching with saturated NH4Cl (10 mL). The reaction was then diluted with brine and extracted with ethyl acetate. The organic extract was then dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Then, the residue was purified by preparative HPLC reverse phase (C-18), eluting with Acetonitrile/Water+0.05% TFA, to give the title compound as a pale yellow solid as an approximate 1:1 mixture of diastereomers. LRMS (ESI) calc'd for (C22H27BrN3O2) [M+H]+ 444.1; found 444.1.

Workup

  1. temperatureto warm to room temperature
  2. customby removing
  3. temperaturecooling baths
  4. stirringstirring an additional 30 minutes
  5. stirringstirred for 1 h
  6. stirringthe reaction mixture was stirred for 30 minutes
  7. custombefore quenching with saturated NH4Cl (10 mL)
  8. additionThe reaction was then diluted with brine
  9. extractionextracted with ethyl acetate
  10. extractionThe organic extract
  11. dry with materialwas then dried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customThen, the residue was purified by preparative HPLC reverse phase (C-18)
  15. washeluting with Acetonitrile/Water+0.05% TFA

Sources & evidence

ORD record
ord-399714ae4513465581ea81fffef86d84
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

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