Dimethylformamide → 1-Benzyl-5-nitro-1H-indazole

HRID 895655

Reaction equation

HRID 895655 reaction equation
CN(C=O)C.[N+:6]([C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2)([O-:8])=[O:7].C(=O)([O-])[O-].[K+].[K+].[CH2:24](Br)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>O.C(OCC)(=O)C>[CH2:24]([N:14]1[C:15]2[C:11](=[CH:10][C:9]([N+:6]([O-:8])=[O:7])=[CH:17][CH:16]=2)[CH:12]=[N:13]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 215015-Nitroindazole

Product 1

HCID 219520821-Benzyl-5-nitro-1H-indazoleYield 41%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

A 12 L 3-necked round-bottomed flask was charged with DMF (2 L), 5-nitroindazole (200 g, 1.22 mol.) and potassium carbonate (186 g, 1.35 mol). Benzyl bromide (230 g, 1.35 mol) was then added to the stirred suspension at a rate as to maintain the temperature below 40° C. Once the addition was complete the mixture was heated to 75° C. for a further 8 hours, the reaction being monitored by TLC (SiO2, 1:1 ethyl acetate:hexanes). The reaction was then cooled to room temperature, water (2 L) added and the resulting slurry stirred at room temperature for 0.5 h. The resulting yellow solids were filtered off and dried at 45° C. and 5 mm Hg vacuum for 48 h. This afforded 424 g of a 1.25:1 mixture of 1- and 2-benzyl-5-nitroindazoles as determined by HPLC analysis (Rt 1-benzyl=14.9 min, Rt 2-benzyl=14.1 min). This material was then split into four approximately 100 g batches and each batch dissolved in acetone (470 mL). Water (156 mL) was then added slowly as a steady stream. After stirring for an additional 1 hour at room temperature the resulting solids were filtered off and vacuum dried. This process afforded a combined total of 126 g (41%) of 1-benzyl-5-nitroindazole, which was 92.1% pure by HPLC analysis, the major contaminant being the 2-benzyl derivative.

Workup

  1. temperatureto maintain the temperature below 40° C
  2. additionOnce the addition
  3. temperatureThe reaction was then cooled to room temperature
  4. filtrationThe resulting yellow solids were filtered off
  5. customdried at 45° C.
  6. wait5 mm Hg vacuum for 48 h
  7. additionThis afforded 424 g of a 1.25:1 mixture of 1- and 2-benzyl-5-nitroindazoles
  8. customas determined by HPLC analysis (Rt 1-benzyl=14.9 min, Rt 2-benzyl=14.1 min)
  9. customThis material was then split into four approximately 100 g batches
  10. dissolutioneach batch dissolved in acetone (470 mL)
  11. additionWater (156 mL) was then added slowly as a steady stream
  12. stirringAfter stirring for an additional 1 hour at room temperature the resulting solids
  13. filtrationwere filtered off
  14. customvacuum dried

Sources & evidence

ORD record
ord-c1a5b885e47f4216aad5a5972704b5f7
Source dataset
uspto-grants-2005_07
Patent number
US06916815B2

Linked notes

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