Hydrochloric Acid → 2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-benzoimidazole

HRID 2078680Notes

Reaction equation

HRID 2078680 reaction equation
C(=[N:14][NH:15][C:16]1[CH:20]=[CH:19][S:18][C:17]=1[C:21]([C:23]1[N:27](COCC2C=CC=CC=2)[C:26]2[CH:37]=[CH:38][CH:39]=[CH:40][C:25]=2[N:24]=1)=O)(C1C=CC=CC=1)C1C=CC=CC=1.Cl.C(O)C.C(=O)([O-])[O-].[K+].[K+]>O.C(OCC)(=O)C.CCCCCCC>[NH:15]1[C:16]2[CH:20]=[CH:19][S:18][C:17]=2[C:21]([C:23]2[NH:27][C:26]3[CH:37]=[CH:38][CH:39]=[CH:40][C:25]=3[N:24]=2)=[N:14]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 11430Potassium CarbonateHCID 57637293[3-(N'-benzhydrylidene-hydrazino)-thiophen-2-yl]-(1-benzyloxymethyl-1H-benzoimidazol-2-yl)-methanone

Product 1

HCID 1354318062-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-benzoimidazole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21899848Ethylacetate heptaneSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of [3-(N′-benzhydrylidene-hydrazino)-thiophen-2-yl]-(1-benzyloxymethyl-1H-benzoimidazol-2-yl)-methanone (300 mg, 0.553 mmol, Example 1D), concentrated hydrochloric acid (4 mL), and ethanol (12 mL) is heated at 75° C. for 260 minutes. The reaction is allowed to cool to ambient temperature, diluted with water (40 mL), and basified with 5% aqueous potassium carbonate. The mixture is extracted with ethyl acetate and the combined extracts washed with water and brine successively. The organic layer is dried over potassium carbonate and concentrated under reduced pressure to give a brown solid. The solid is chromatographed on silica. Step gradient elution with 70% ethyl acetate/heptane, 80% ethyl acetate/heptane, and 90% ethyl acetate/heptane provided an orange solid. Trituration with ethyl acetate/heptane gave 2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-benzoimidazole as a beige powder: TLC Rf 0.28 (silica, 75% ethyl acetate/heptane); LC/MS: (M+H 241.0, RT=2.15 minutes); 1H NMR [(CD3)2SO), 300 MHz]: δ 13.56 (s, 1H), 12.94 (2, 1h), 7.78 (d, 1H, 5.3 Hz), 7.69 (d, 1H, 7.3 Hz), 7.48 (d, 1H, 7.0 Hz), 7.22-7.15 (m, 3H).

Workup

  1. temperatureto cool to ambient temperature
  2. extractionThe mixture is extracted with ethyl acetate
  3. washthe combined extracts washed with water and brine successively
  4. dry with materialThe organic layer is dried over potassium carbonate
  5. concentrationconcentrated under reduced pressure
  6. customto give a brown solid
  7. customThe solid is chromatographed on silica
  8. washStep gradient elution with 70% ethyl acetate/heptane, 80% ethyl acetate/heptane, and 90% ethyl acetate/heptane
  9. customprovided an orange solid

Sources & evidence

ORD record
ord-9b0710a4c8234b6ebb31e330e9a110a0
Source dataset
uspto-grants-2011_04
Patent number
US07928231B2

Reaction notes

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