Water → 1-(3-fluorobenzyl)-5-nitro-1H-indazole

HRID 1072070Notes

Reaction equation

HRID 1072070 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][N:8]=[CH:7]2)([O-:3])=[O:2].[F:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=1)[CH2:17]Cl.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[F:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=1)[CH2:17][N:9]1[C:10]2[C:6](=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:12][CH:11]=2)[CH:7]=[N:8]1

Participants

6

Reactant 4

HCID 962WaterHCID 99743-Fluorobenzyl chlorideHCID 11430Potassium CarbonateHCID 215015-Nitroindazole

Product 1

HCID 219664901-(3-fluorobenzyl)-5-nitro-1H-indazoleYield 33%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 5-nitro-1H-indazole (8.15 gm, 50 mmole), m-fluoro-benzyl chloride (7.95 gm, 1.1 equiv), K2CO3 (7.59 gm, 1.1 equiv), and KI (8.47 gm, 1.02 equiv) in dry DMF (75 mL) was heated at 70° C. overnight. After cooling to RT, water (75 mL) was slowly added to give a precipitate that consisted of about a one to one mixture of isomers [HPLC Ret Time: 1.92 (1-substitued isomer vs. 2.03 (2-substituted isomer) YMC C18 S5 4.6×50 mm, 3 min gradient, 4 mL/min]. This was collected by filtration and washed with water. The solid was crystallized twice from acetone/water to afford the desired 1-(3-fluoro-benzyl)-5-nitro-1H-indazole (4.47 gm, 33%). A suspension of this material (3.00 gm, 11.1) and 10% Pd/C (3.00 gm) in EtOH (21 mL) was kept under an H2 atmosphere (balloon) for 24 hr. The catalyst was removed by filtration and the solvent was evaporated to leave the product as a solid (2.4 gm, 90%). 1H NMR (CDCl3): δ 3.61 (br s, 2H), 5.52 (s, 2H), 6.81-7.85 (m, 7H), 7.85 (s, 1H); MS: 242 (M+H)+; HPLC Ret Time: 1.03 min (YMC Xterra ODS S7, 3.0×50 mm column, 2 min gradient, 5 mL/min).

Workup

  1. temperatureAfter cooling to RT
  2. customto give a precipitate that
  3. additionconsisted of about a one to one mixture of isomers [HPLC Ret Time
  4. customC18 S5 4.6×50 mm, 3 min gradient, 4 mL/min
  5. filtrationThis was collected by filtration
  6. washwashed with water
  7. customThe solid was crystallized twice from acetone/water

Sources & evidence

ORD record
ord-bba94e276ce14a6f913e3c72d0cf2f7e
Source dataset
uspto-grants-2005_06
Patent number
US06908916B2

Reaction notes

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