Sodium hydride → 1-Cyclopropylmethyl-3-(1-methyl-4-piperidinyl)-1H-indazole hydrobromide

HRID 1382549Notes

Reaction equation

HRID 1382549 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH2:9][CH2:8][CH:7]([C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:12][N:11]=2)[CH2:6][CH2:5]1.Cl[CH2:20][CH:21]1[CH2:23][CH2:22]1.[BrH:24].CCOCC>CN(C)C=O.CCOCC>[BrH:24].[CH:21]1([CH2:20][N:12]2[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:10]([CH:7]3[CH2:6][CH2:5][N:4]([CH3:3])[CH2:9][CH2:8]3)=[N:11]2)[CH2:23][CH2:22]1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 80013(Chloromethyl)cyclopropaneHCID 86739792Ether hydrobromideHCID 178480237HCID 178480237, compound

Product 1

HCID 140325091-Cyclopropylmethyl-3-(1-methyl-4-piperidinyl)-1H-indazole hydrobromideYield 32%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent3×

Procedure

To a stirred mixture of 1.19 g of sodium hydride (50% oil dispersion) in 65 ml of dimethylformamide was added, dropwise, 4.0 g of 3-(1-methyl-4-piperidinyl)-1H-indazole in 20 ml of hot dimethylformamide. The mixture was stirred for 1 hr at ambient temperature and then 1.40 g of chloromethylcyclopropane in 10 ml of dimethylformamide was added dropwise. The reaction mixture was stirred for 21/2 days at ambient temperature. The reaction mixture was quenched with water, extracted with ethyl acetate, washed with water, dried over anhydrous magnesium sulfate and the solvent was removed in vacuo to yield an oil. The oil was dissolved in ether and saturated hydrogen bromide/ether solution was added dropwise to precipitate a salt. The salt was recrystallized from toluene and ethyl acetate to yield 2.8 g (32%) of product, mp 177°-179° C.

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred for 21/2 days at ambient temperature
  3. customThe reaction mixture was quenched with water
  4. extractionextracted with ethyl acetate
  5. washwashed with water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customthe solvent was removed in vacuo
  8. customto yield an oil
  9. customto precipitate a salt
  10. customThe salt was recrystallized from toluene and ethyl acetate

Sources & evidence

ORD record
ord-62f0d0e4ee2149d68b251b2347145f72
Source dataset
uspto-grants-1989_02
Patent number
US04806649

Reaction notes

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