Methyl Isocyanate → HCID 178485842, compound

HRID 2182372Notes

Reaction equation

HRID 2182372 reaction equation
[CH3:1][C:2]1[C:16]([CH3:17])=[CH:15][C:5]2[NH:6][C:7]([C:9]3[C:13]([NH2:14])=[CH:12][NH:11][N:10]=3)=[N:8][C:4]=2[CH:3]=1.[CH3:18][N:19]=[C:20]=[O:21]>O1CCCC1>[CH3:17][C:16]1[C:2]([CH3:1])=[CH:3][C:4]2[NH:8][C:7]([C:9]3[C:13]([NH:14][C:20]([NH:19][CH3:18])=[O:21])=[CH:12][NH:11][N:10]=3)=[N:6][C:5]=2[CH:15]=1

Participants

4

Reactant 2

HCID 12228Methyl IsocyanateHCID 178422296HCID 178422296, compound

Product 1

HCID 178485842HCID 178485842, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3-(5,6-dimethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-ylamine [0.500 g, Example 233(c)] in tetrahydrofuran (5 ml) was treated with methyl isocyanate (0.502 ml) and the mixture stirred at ambient temperature for 16 hours. The mixture was then concentrated in vacuo and the residue was redissolved in 1N potassium hydroxide in a mixture of methanol and tetrahydrofuran (1:3, 5 ml). The mixture was stirred for a further 1 hour, then concentrated and then partitioned between ethyl acetate and water. The aqueous layer was extracted three times with ethyl acetate and the combined organic extracts were washed with brine, then dried over magnesium sulfate, and then evaporated. The residue was subjected to flash column chromatography on silica eluting initially with a mixture of ethyl acetate and hexane (1:1, v/v) and then with ethyl acetate to afford 1-[3-(5,6-dimethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-3-methyl-urea (230 mg) as a white solid. MS: 269 (M+H)+. HPLC (METHOD D1): RT=5.97 minutes. (b) 1-[3-(5,6-Dimethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-3-isopropyl-urea

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. dissolutionthe residue was redissolved in 1N potassium hydroxide in a mixture of methanol and tetrahydrofuran (1:3, 5 ml)
  3. stirringThe mixture was stirred for a further 1 hour
  4. concentrationconcentrated
  5. custompartitioned between ethyl acetate and water
  6. extractionThe aqueous layer was extracted three times with ethyl acetate
  7. washthe combined organic extracts were washed with brine
  8. dry with materialdried over magnesium sulfate
  9. customevaporated
  10. additionThe residue was subjected to flash column chromatography on silica eluting initially with a mixture of ethyl acetate and hexane (1:1

Sources & evidence

ORD record
ord-2dbb6493dc3345a09dee8d3d8cf71b0e
Source dataset
uspto-grants-2005_05
Patent number
US06897208B2

Reaction notes

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