Water → 5-Benzimidazol-2-Yl-3-(4-Fluorophenyl)-1H-Indazole

HRID 1272756Notes

Reaction equation

HRID 1272756 reaction equation
[N+:1]([C:4]1[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=1[NH2:6])([O-])=O.C([N:14]1[C:22]2[C:17](=[CH:18][C:19]([C:23](Cl)=O)=[CH:20][CH:21]=2)[C:16]([C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)=[N:15]1)(=O)C.O>N1C=CC=CC=1>[N:6]1[C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[NH:1][C:23]=1[C:19]1[CH:18]=[C:17]2[C:22](=[CH:21][CH:20]=1)[NH:14][N:15]=[C:16]2[C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 962WaterHCID 69462-NitroanilineHCID 224802271-acetyl-3-(4-fluorophenyl)-1H-indazole-5-carbonyl chloride

Product 1

HCID 224802015-Benzimidazol-2-Yl-3-(4-Fluorophenyl)-1H-IndazoleYield 17%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a solution of 2-nitroaniline (92 mg, 0.67 mmol) in pyridine (4 mL) was added 1-acetyl-3-(4-fluorophenyl)-1H-indazole-5-carbonyl chloride (200 mg, 0.67 mmol). The reaction was stirred at room temperature overnight when water (30 mL) was added and the solid filtered and dried in a vacuum oven (45° C.). The solid was then taken up in ethyl acetate (20 mL)/ethanol (20 mL) and a scoup of palladium on carbon added. The resulting heterogenous solution was then subjected to an atmosphere of hydrogen. After stirring overnight, the solution was filtered and concentrated to an oil under vacuo and taken up in 4 N HCl (80 mL) which was refluxed for 12 hours. The reaction was quenched with saturated NaHCO3 and the product collected as a solid. The pure product was isolated after chromatography on silica gel eluting with 7% methanol in methylene chloride. (37 mg, 17% yield). 1H NMR (DMSO-d6) δ 13.6 (br s, 1H), 8.86 (s, 1H), 8.29 (d, 1H), 8.16–8.10 (m, 2H), 7.76 (d, 1H), 7.64 (dd, 2H), 7.45 (t, 2H), 7.24 (dd, 2H); ES-MS (m/z) 329 [M+1]+.

Workup

  1. additionwas added
  2. filtrationthe solid filtered
  3. customdried in a vacuum oven (45° C.)
  4. additiona scoup of palladium on carbon added
  5. filtrationthe solution was filtered
  6. concentrationconcentrated to an oil under vacuo
  7. temperaturewas refluxed for 12 hours
  8. customThe reaction was quenched with saturated NaHCO3
  9. customthe product collected as a solid
  10. customThe pure product was isolated after chromatography on silica gel eluting with 7% methanol in methylene chloride

Sources & evidence

ORD record
ord-4e7ccd9893ff4b8ca0f582f4c313205f
Source dataset
uspto-grants-2007_04
Patent number
US07208513B2

Reaction notes

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