1,1'-Carbonyldiimidazole → HCID 9999882, compound

HRID 1437826Notes

Reaction equation

HRID 1437826 reaction equation
[S:1]1[CH:5]=[C:4]([C:6]2[NH:7][C:8]3[CH:14]=[C:13]([NH2:15])[CH:12]=[CH:11][C:9]=3[N:10]=2)[N:3]=[CH:2]1.[C:16]([N:23]1[CH:27]=[CH:26]N=C1)(N1C=CN=C1)=[O:17].[F:28][C:29]1[CH:30]=[C:31]([CH:35]=[CH:36][CH:37]=1)CCN>CN(C)C=O>[F:28][C:29]1[CH:37]=[C:36]([CH2:26][CH2:27][NH:23][C:16]([NH:15][C:13]2[CH:12]=[CH:11][C:9]3[N:10]=[C:6]([C:4]4[N:3]=[CH:2][S:1][CH:5]=4)[NH:7][C:8]=3[CH:14]=2)=[O:17])[CH:35]=[CH:31][CH:30]=1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 1349122-(1,3-Thiazol-4-yl)-1H-benzimidazol-6-amineHCID 5339282-(3-Fluorophenyl)ethanamine

Product 1

HCID 9999882HCID 9999882, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-thiazol-4-yl-3H-benzoimidazol-5-ylamine (1-5, 100 mg, 0.46 mmol) in N,N-dimethylformamide (2 mL). The 1,1′-carbonyldiimidazole (CDI, 82 mg, 0.51 mmol) was added in one sum to the solution and was stirred for two hours. The 3-fluorophenethylamine (2-1, 72 uL, 0.56 mmol) was added to the reaction mixture via pipet and stirred to completion by LCMS analysis. The LCMS indicated that the dibenzimidazole urea was the by-product. The reaction mixture was partitioned between ethyl acetate and dilute sodium bicarbonate solution. The insoluble urea by-product was removed by vacuum filtration of the layers and the aqueous was extracted (3×10 mL) with ethyl acetate. The organic layer was washed twice with water, once with brine, separated, dried (Na2SO4), filtered, and concentrated in vacuo. The resulting red solid was triturated in ethyl acetate/hexanes mixtures to afford the pure 1-[2-(3-fluoro-phenyl)-ethyl]-3-(2-thiazol-4-yl-3H-benzoimidazol-5-yl)-urea as a gray solid (2-77); 1H NMR (500 MHz, DMSO-d6) δ 12.72 (s, 1H), 9.31 (t, 1H, J=2.0 Hz), 8.52 (s, 1H), 8.34 (d, 1H, J=2.0 Hz), 7.87 (d, 1H, J=1.0 Hz), 7.47 (d, 1H, J=8.5 Hz), 7.35 (d, 1H, J=6.5 Hz), 7.11 (d, 2H, J=8.0 Hz), 7.04 (dt, 1H, J=8.5, 2.0 Hz), 6.96 (dd, 1H, J=8.5, 2.0 Hz), 6.06 (m, 1H), 3.38 (q, 2H, J=7.0 Hz), 2.80 (t, 2H, J=7.0 Hz).

Workup

  1. stirringstirred to completion by LCMS analysis
  2. customThe reaction mixture was partitioned between ethyl acetate and dilute sodium bicarbonate solution
  3. customThe insoluble urea by-product was removed by vacuum filtration of the layers
  4. extractionthe aqueous was extracted (3×10 mL) with ethyl acetate
  5. washThe organic layer was washed twice with water, once with brine
  6. customseparated
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resulting red solid was triturated in ethyl acetate/hexanes mixtures

Sources & evidence

ORD record
ord-93a96cc464094c679d4614df2423b627
Source dataset
uspto-grants-2009_11
Patent number
US07622592B2

Reaction notes

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