Water → 1-(3-methoxypropyl)-6-nitro-1H-indazole

HRID 660364

Reaction equation

HRID 660364 reaction equation
[N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[N:9][NH:10]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].CS(O[CH2:18][CH2:19][CH2:20][O:21][CH3:22])(=O)=O.C([O-])([O-])=O.[K+].[K+].O>CC#N>[CH3:22][O:21][CH2:20][CH2:19][CH2:18][N:10]1[C:11]2[C:7](=[CH:6][CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:12]=2)[CH:8]=[N:9]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 242396-NitroindazoleHCID 116939633-Methoxypropyl methanesulfonate

Product 1

HCID 596309911-(3-methoxypropyl)-6-nitro-1H-indazoleYield 46%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 6-nitro-1H-indazole (50 g, 0.307 mol), 3-methoxypropyl methanesulfonate (54.3 g, 0.323 mol) and K2CO3 (127 g, 0.921 mol) in CH3CN (1.5 L) was heated at 60° C. overnight. Water (1 L) was added and the CH3CN was removed under reduced pressure and the aqueous residue was extracted with EtOAc (3×500 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography on silica gel to give 1-(3-methoxypropyl)-6-nitro-1H-indazole (33 g, 46% yield). 1H NMR (400 MHz, CDCl3): δ8.47 (s, 1H), 8.13 (s, 1H), 8.01-7.99 (dd, J=8.8, 2.0 Hz, 1H), 7.83-7.81 (d, J=8.8 Hz, 1H), 4.61-4.57 (t, J=6.4 Hz, 2H), 3.29 (s, 3H), 3.26-3.23 (t, J=5.6 Hz, 2H), 2.23-2.17 (m, 2H).

Workup

  1. customthe CH3CN was removed under reduced pressure
  2. extractionthe aqueous residue was extracted with EtOAc (3×500 mL)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-aa78929fb88d4d59b52175c62d3f59eb
Source dataset
uspto-grants-2011_12
Patent number
US08084485B2

Linked notes

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