Water → HCID 22733808, compound

HRID 322099Notes

Reaction equation

HRID 322099 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:12]=[C:11]2[C:7]([C:8]([CH2:13][CH3:14])=[N:9][NH:10]2)=[CH:6][CH:5]=1.[CH:15]1(Br)[CH2:19][CH2:18][CH2:17][CH2:16]1.O>CN(C=O)C>[Br:3][C:4]1[CH:12]=[C:11]2[C:7]([C:8]([CH2:13][CH3:14])=[N:9][N:10]2[CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8728BromocyclopentaneHCID 24758Sodium hydrideHCID 178437983HCID 178437983, compound

Product 1

HCID 22733808HCID 22733808, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2.46 g (61.4 mmol, 1.05 equiv) sodium hydride, 60% oil dispersion, was added in 0.5 g portions to a 10° C. solution of 13.17 g (58.5 mmol, 1.0 equiv) 6-bromo-3-ethyl-1H-indazole in 500 mL anhydrous DMF. The mixture was stirred at room temperature for 20 minutes, then a solution of 8.8 mL (81.9 mmol, 1.4 equiv) cyclopentyl bromide in 10 mL anhydrous DMF was added dropwise. After 18 hours, the reaction mixture was poured into 2 L H2O and extracted 2×1 L ethyl acetate. The organic extracts were combined, washed 2×750 mL H2O, 1×500 mL brine, and dried over Na2SO4. Filtration, concentration of filtrate and drying gave 20.7 g of crude product, which was purified on a silica gel column (1.1 kg silica gel, 3% ethyl acetate/hexanes) to give 10.6 g (62%) of an amber liquid: IR (CHCl3)2972, 2875, 1606, 1501, 1048 cm−1; 1H NMR (300 MHz, CDCl3) d 7.56 (d, 1H, J=1.3 Hz), 7.52 (d, 1H, J=8.7 Hz), 7.17 (dd, 1H, J=1.5, 8.5 Hz), 4.83 (quintet, 1H, J=7.6 Hz), 2.96 (q, 2H, J=7.6 Hz), 2.15 (m, 4H), 2.0 (m, 2H), 1.65 (m, 2H), 1.36 (t, 3H, J=7.7 Hz); MS (thermospray, NH4OAc) m/z 295/293 (M+H+, base); Anal. calcd for C14H17N2Br: C, 57:35; H, 5.84; N, 9.55. Found: C, 57.48; H, 5.83; N, 9.90.

Workup

  1. waitAfter 18 hours
  2. extractionextracted 2×1 L ethyl acetate
  3. washwashed 2×750 mL H2O, 1×500 mL brine
  4. dry with materialdried over Na2SO4
  5. filtrationFiltration, concentration of filtrate
  6. customdrying
  7. customgave 20.7 g of crude product, which
  8. customwas purified on a silica gel column (1.1 kg silica gel, 3% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-375e3a87d05a4f9694aabe6c142a9205
Source dataset
uspto-grants-2001_04
Patent number
US06211222B1

Reaction notes

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