Dimethylformamide → N-(6-formyl-1-isoquinolinyl)benzamide

HRID 2304232Notes

Reaction equation

HRID 2304232 reaction equation
[Li]CCCC.Br[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[C:13]([NH:17][C:18](=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[N:12][CH:11]=[CH:10]2.CN(C)[CH:28]=[O:29]>O1CCCC1>[CH:28]([C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[C:13]([NH:17][C:18](=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[N:12][CH:11]=[CH:10]2)=[O:29]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 22665824N-(6-bromo-1-isoquinolinyl)benzamideHCID 178418339Butyllithium

Product 1

HCID 22665740N-(6-formyl-1-isoquinolinyl)benzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred solution of 29 mL of n-BuLi (1.6 M in hexane) in 40 mL of dry tetrahydrofuran under a nitrogen atmosphere at −78° C. was added dropwise a solution of 2.5 g of 1e in 60 mL of dry tetrahydrofuran over a period of 15 min. After stirring for 30 min a mixture of 34 mL of N,N-dimethylformamide and 20 mL of tetrahydrofuran was added fast. The cooling bath was removed, the reaction mixture was allowed to come to 0° C. and was poured into ice cold aqueous hydrochloric acid (60 mL, 0.5 N). The mixture was adjusted to pH 6, brine was added and the mixture was extracted with ethyl acetate. The ethyl acetate extract was dried (MgSO4) and concentrated under reduced pressure. Purification on silica gel (toluene/ethyl acetate:3/1) gave 1.3 g of aldehyde 1f. 1H-NMR 200 MHz (CDCl3) δ: 7.12 (1H, d, J=7 Hz). 7.40-8.51 (9H, m), 9.26 (1H, d, J=8 Hz), 10.23 (1H, s).

Workup

  1. additionwas added fast
  2. customThe cooling bath was removed
  3. customto come to 0° C.
  4. additionwas poured into ice cold aqueous hydrochloric acid (60 mL, 0.5 N)
  5. additionwas added
  6. extractionthe mixture was extracted with ethyl acetate
  7. extractionThe ethyl acetate extract
  8. dry with materialwas dried (MgSO4)
  9. concentrationconcentrated under reduced pressure
  10. customPurification on silica gel (toluene/ethyl acetate:3/1)

Sources & evidence

ORD record
ord-b8e5d704d27f4606a1be570fc5bd43f9
Source dataset
uspto-grants-2002_08
Patent number
US06432955B1

Reaction notes

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