Dimethylformamide → HCID 178434286, compound

HRID 218474Notes

Reaction equation

HRID 218474 reaction equation
C([Li])(C)(C)C.Br[C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][N:11]=[C:10]2[CH3:16].CN(C)[CH:19]=[O:20]>CCCCC.O1CCCC1>[CH3:16][C:10]1[C:9]2[C:13](=[CH:14][CH:15]=[C:7]([CH:19]=[O:20])[CH:8]=2)[NH:12][N:11]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 178418306HCID 178418306, compoundHCID 178434225HCID 178434225, compound

Product 1

HCID 178434286HCID 178434286, compound

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To chilled tetrahydrofuran (600 mL) at −78° C., under Argon, was added 200 mL of a 1.7M solution of tert-butyllithium in n-pentane. After 15 minutes at −78° C., a solution of 22.4 g (106.13 mmol) 5-bromo-3-methyl-1H-indazole (commercially available, or see WO 2006/081230, 68-69) in 300 mL tetrahydrofuran was added dropwise at such a rate that the temperature of the solution did not exceed −70° C. The mixture was stirred for 30 minutes before 24.5 mL N,N-dimethylformamide was added dropwise. After 20 minutes the cooling bath was removed and stirring continued for 1 hour before 41 mL water was added carefully. A further 201 mL water was added and the mixture was extracted with ethyl acetate. The organic extract was washed with saturated sodium chloride solution and dried over sodium sulfate. The solvents were distilled off to give 18.5 g crude 3-methyl-1H-indazole-5-carbaldehyde, which was used without purification. 1H-NMR (DMSO-d6): δ=13.13 (br s, 1H), 10.01 (s, 1H), 8.40 (s, 1H), 7.81 (d, 1H), 7.58 (d, 1H), 2.56 (s, 3H) ppm. MS (ES+): 161.34 (M++1, 100%).

Workup

  1. additionwas added dropwise at such a rate that the temperature of the solution
  2. customdid not exceed −70° C
  3. additionwas added dropwise
  4. customAfter 20 minutes the cooling bath was removed
  5. waitcontinued for 1 hour before 41 mL water
  6. additionwas added carefully
  7. additionA further 201 mL water was added
  8. extractionthe mixture was extracted with ethyl acetate
  9. extractionThe organic extract
  10. washwas washed with saturated sodium chloride solution
  11. dry with materialdried over sodium sulfate
  12. distillationThe solvents were distilled off

Sources & evidence

ORD record
ord-aa8083a71eb94c11a187f96139e480e3
Source dataset
uspto-grants-2012_06
Patent number
US08198456B2

Reaction notes

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