Hydrochloric Acid → HCID 135430319, compound

HRID 2111160Notes

Reaction equation

HRID 2111160 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]=[C:38]([O:41][CH3:42])[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>[CH3:42][O:41][C:38]1[CH:39]=[CH:40][C:25]2[N:24]=[C:23]([C:21]3[C:17]4[S:18][CH:19]=[CH:20][C:16]=4[NH:15][N:14]=3)[NH:27][C:26]=2[CH:37]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 11430Potassium CarbonateHCID 57637406HCID 57637406, compound

Product 1

HCID 135430319HCID 135430319, compound

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-6-methoxy-1H-benzoimidazol-2-yl)-methanone (300 mg, 0.553 mmol, Example 2C), concentrated hydrochloric acid (4 mL), and ethanol (12 mL) is heated at 75° C. with stirring 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 6-methoxy-2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-benzoimidazole as a beige powder: TLC Rƒ0.28 (silica, 75% ethyl acetate/heptane); LC/MS: M+H 241.0, RT=2.15 minutes; 1H NMR [(CD3)2SO), 300 MHz]: two species observed (ca. 60:40), presumed to be slowly exchanging imidazole tautomers, with chemical shifts of resolved resonances reported as major (minor); δ 13.48 (13.51) brs (1H; NH of benzimidazole), 12.79 brs (1H; NH of pyrazole), 7.77 d (1H, J=5 Hz; H-α of thiophene), 7.57 (7.35) d (1H, J=8.5 Hz; H-7 of benzimidazole), 7.20 d (1H, J=5 Hz; H-β of thiophene), 6.96 (7.25) d (1H, J=2 Hz; H-4 of benzimidazole), 6.82 m (1H; H-6 of benzimidazole), 3.80 (3.32) s (3H; methoxy). Chemical shifts are referenced to internal dimethyl sulfoxide-D5 (δ 2.50).

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-0bdb975fdd0c4e38b514e8095733c808
Source dataset
uspto-grants-2009_04
Patent number
US07518000B2

Reaction notes

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