Acetic Acid → 3-(1H-benzoimidazol-2-yl)-6-(3-methoxy-4-methoxymethoxy-phenyl)-1H-indazole

HRID 724366Notes

Reaction equation

HRID 724366 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[CH:21]=[C:20]3[C:16]([C:17]([CH:22]=O)=[N:18][NH:19]3)=[CH:15][CH:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH2:10][O:11][CH3:12].C(O)(=O)C.[NH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[NH2:35]>C(O)C.O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[NH:28]1[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[N:35]=[C:22]1[C:17]1[C:16]2[C:20](=[CH:21][C:13]([C:5]3[CH:6]=[CH:7][C:8]([O:9][CH2:10][O:11][CH3:12])=[C:3]([O:2][CH3:1])[CH:4]=3)=[CH:14][CH:15]=2)[NH:19][N:18]=1

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 7243O-PhenylenediamineHCID 178497461HCID 178497461, compound

Product 1

HCID 1358393153-(1H-benzoimidazol-2-yl)-6-(3-methoxy-4-methoxymethoxy-phenyl)-1H-indazoleYield 54.6%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

6-(3-Methoxy-4-methoxymethoxy-phenyl)-1H-indazole-3-carbaldehyde (from Example 1(a), step (vi)) (20 mg, 0.064 mmol, 1 equiv) was dissolved in degassed 1:1 MeOH-water (0.7 mL) and was treated with acetic acid (19 μL, 5 equiv), 1,2-diaminobenzene (8.3 mg, 1.2 equiv) and copper(II) acetate (18 mg, 1.4 equiv) at 23° C. The mixture stirred for 30 min, was diluted with ethanol (3 mL) and water (2 mL) and was treated with a bubbling stream of SH2 for 3 min, which gave a black precipitate. The mixture was allowed to stir for 12 h. The mixture was filtered and concentrated. Purification by silica gel chromatography (6:4 ethyl acetate-hexane) gave 3-(1H-benzoimidazol-2-yl)-6-(3-methoxy-4-methoxymethoxy-phenyl)-1H-indazole as a solid (14 mg, 54%); Rf sm 0.39, p 0.24 (ethyl acetate-hexane 6:4); 1H NMR (CDCl3) δ 8.69 (d, 1H, J=8 Hz), 7.70 (bs, 2H), 7.58 (s, 1H), 7.53 (d, 1H, J=8 Hz), 7.30–7.15 (m, 7H), 5.30 (s, 2H), 3.97 (s, 3H), 3.58 (s, 3H); MS (ES) [m+H]/z Calc'd 401. found 401. [m−H]/z Calc'd 399. found 399.

Workup

  1. customin degassed 1:1 MeOH-water (0.7 mL)
  2. additionwas treated with a bubbling stream of SH2 for 3 min
  3. customwhich gave a black precipitate
  4. stirringto stir for 12 h
  5. filtrationThe mixture was filtered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (6:4 ethyl acetate-hexane)

Sources & evidence

ORD record
ord-bd8ce4d471164197a5c3ed64b33b7e38
Source dataset
uspto-grants-2006_11
Patent number
US07141587B2

Reaction notes

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