Dimethylformamide → HCID 23585448, compound

HRID 1897868Notes

Reaction equation

HRID 1897868 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[CH2:11](Br)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CN(C=O)C>C(OCC)(=O)C.O>[CH2:11]([N:5]1[CH:4]=[C:3]2[C:7]([CH:8]=[CH:9][CH:10]=[C:2]2[Br:1])=[N:6]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 7498Benzyl BromideHCID 223525484-bromo-1H-indazole

Product 1

HCID 23585448HCID 23585448, compoundYield 65.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Bromoindazole of Example 2 (17.4 g, 0.088 M), benzyl bromide (22.7 g, 0.132 M) and DMF (35 mL) were heated to about 50° C. for 25 hours (HPLC: 15:1 ratio of 2-N and 1-N isomers). The mixture was cooled to ambient temperature and diluted with ethyl acetate (160 mL) and water (100 mL). The organic layer was separated, washed with aqueous sodium bicarbonate (5%, 100 mL). The organic layer was separated and concentrated under reduced pressure. The residue was diluted with isopropanol (160 mL) and concentrated under reduced pressure to a volume of about 120 mL. The mixture was heated to 50° C. to dissolve the solid and diluted with water (70 mL) to precipitate the product. The slurry was cooled to 0° C. and the precipitate was filtered off. The solid was washed with a mixture of IPA and Water (1:1, 50 mL), and dried at 50° C. to provide the titled compound (16.5 g, 77%, which contained less than 2% of 1-N-isomer by HPLC): 1H NMR (CDCl3, δ, ppm) 5.56 (s, 2H), 7.11 (m, 1H), 7.21 (d, J=7.2 Hz, 1H), 7.24-7.39 (m, 5H), 7.65 (d, J=8.6 Hz, 1H), 7.88 (s, 1H).

Workup

  1. customThe organic layer was separated
  2. washwashed with aqueous sodium bicarbonate (5%, 100 mL)
  3. customThe organic layer was separated
  4. concentrationconcentrated under reduced pressure
  5. additionThe residue was diluted with isopropanol (160 mL)
  6. concentrationconcentrated under reduced pressure to a volume of about 120 mL
  7. temperatureThe mixture was heated to 50° C.
  8. dissolutionto dissolve the solid
  9. additiondiluted with water (70 mL)
  10. customto precipitate the product
  11. temperatureThe slurry was cooled to 0° C.
  12. filtrationthe precipitate was filtered off
  13. washThe solid was washed with a mixture of IPA and Water (1:1, 50 mL)
  14. customdried at 50° C.

Sources & evidence

ORD record
ord-820f0fef7a114c92813ac867a9b89c41
Source dataset
uspto-grants-2013_08
Patent number
US08519186B2

Reaction notes

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