Potassium Hydroxide → HCID 178494651, compound

HRID 380398Notes

Reaction equation

HRID 380398 reaction equation
[CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([CH2:12][O:13][CH3:14])[NH:11][C:7]=2[C:6]([C:15](=O)[CH2:16][C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)=[CH:5][CH:4]=1.O.NN.[OH-].[K+]>C(O)COCCO.ClCCl>[CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([CH2:12][O:13][CH3:14])[NH:11][C:7]=2[C:6]([CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 178494652HCID 178494652, compound

Product 1

HCID 178494651HCID 178494651, compoundYield 108.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8117Diethylene GlycolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1-(7-methoxy-2-methoxymethyl-3H-benzimidazol-4-yl)-2-(4-pyridyl)ethanone (0.92 g, Example 4), hydrazine hydrate (0.8 ml, 98%) and potassium hydroxide (1.6 g) in diethylene glycol (10 ml) was heated at 100° C. for 5 minutes. The resulting clear solution was the heated at 160° C. for 1 hour, then heated at 180° C. for 2 hours whilst removing water at intervals from an attached air condenser. The red solution was cooled to room temperature then poured into water (200 ml). The mixture was extracted three times with dichloromethane (100 ml). The combined extracts were dried over magnesium sulphate and then evaporated. The residue was subjected to flash chromatography on silica eluting with a mixture of methanol and dichloromethane (5:95, v/v). Fractions containing the required product were combined and evaporated. The resulting solid was combined with material similarly prepared from 0.47 g of 1-(7-methoxy-2-methoxymethyl-3H-benzimidazol-4-yl)-2-(4-pyridyl)ethanone and dissolved in dichloromethane (50 ml). The solution was washed with water (100 ml) then dried over magnesium sulphate and then evaporated. The residual white solid (1.03 g) was recrystallised from toluene to give the title compound (0.95 g) as a white solid, m.p. 154-156° C. [Elemental analysis:—C,68.09; H,6.43; N,13.87%. Calculated:13 C,68.67; H,6.44; N,14.13%].

Workup

  1. temperatureheated at 160° C. for 1 hour
  2. temperatureheated at 180° C. for 2 hours
  3. customwhilst removing water at intervals from an attached air condenser
  4. temperatureThe red solution was cooled to room temperature
  5. additionthen poured into water (200 ml)
  6. extractionThe mixture was extracted three times with dichloromethane (100 ml)
  7. dry with materialThe combined extracts were dried over magnesium sulphate
  8. customevaporated
  9. additionThe residue was subjected to flash chromatography on silica eluting with a mixture of methanol and dichloromethane (5:95
  10. additionFractions containing the required product
  11. customevaporated
  12. customsimilarly prepared from 0.47 g of 1-(7-methoxy-2-methoxymethyl-3H-benzimidazol-4-yl)-2-(4-pyridyl)ethanone
  13. washThe solution was washed with water (100 ml)
  14. dry with materialthen dried over magnesium sulphate
  15. customevaporated
  16. customThe residual white solid (1.03 g) was recrystallised from toluene

Sources & evidence

ORD record
ord-f434728ba35f4719b850a8784d16223e
Source dataset
uspto-grants-2001_10
Patent number
US06303600B1

Reaction notes

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