1-Butanol → 4-Methoxy-1H-indazol-3-amine

HRID 1808546Notes

Reaction equation

HRID 1808546 reaction equation
F[C:2]1[CH:9]=[CH:8][CH:7]=[C:6](OC)[C:3]=1[C:4]#[N:5].[OH2:12].[NH2:13][NH2:14].O.[CH2:16](O)CCC>>[CH3:16][O:12][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]2[C:3]=1[C:4]([NH2:5])=[N:13][NH:14]2

Participants

5

Reactant 4

HCID 2631-ButanolHCID 962WaterHCID 24654Hydrazine hydrate (1:1)HCID 5231012-Fluoro-6-methoxybenzonitrile

Product 1

HCID 185260534-Methoxy-1H-indazol-3-amine

Procedure

A mixture of 2-fluoro-6-(methyloxy)benzonitrile (available from Apollo) (10 g, 66 mmol) and hydrazine hydrate (9.63 mL, 198 mmol) in n-butanol (100 mL) was heated at reflux under nitrogen for 18 hours. The reaction mixture was allowed to cool, water (300 mL) was added, and the organic phase was removed. The solid in the aqueous phase was collected by filtration and dried in vacuo at 40° C. to give a white solid (0.6 g). The butanol phase was evaporated in vacuo, and the residue and the aqueous mother liquors were combined and extracted using ethyl acetate (2×200 mL). The combined ethyl acetate extractions were dried over magnesium sulphate and evaporated in vacuo. The residue was dissolved in DCM and applied to a 100 g silica cartridge. This was eluted with cyclohexane (500 ml), cyclohexane-ethyl acetate (1:1 v/v, 500 mL) and ethyl acetate (500 mL). The required fractions were combined and evaporated in vacuo to give the title compound (9.92 g, 92%) as an off-white solid. LCMS (System A) RT=0.5 min, ES+ve m/z 164 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux under nitrogen for 18 hours
  3. temperatureto cool
  4. customthe organic phase was removed
  5. filtrationThe solid in the aqueous phase was collected by filtration
  6. customdried in vacuo at 40° C.

Sources & evidence

ORD record
ord-f81c2cc921ab4a2e8513ee77bc0e20b0
Source dataset
uspto-grants-2013_01
Patent number
US08357716B2

Reaction notes

Loading…