Tetrahydrofuran → HCID 178425823, compound

HRID 2099236Notes

Reaction equation

HRID 2099236 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:8]=[C:9]([CH:16]=[CH:17][C:18]=2[CH3:19])[C:10]([NH:12][CH:13]2[CH2:15][CH2:14]2)=[O:11])[CH:5]=[N:4][C:3]=1[C:20]#[N:21].[CH:22]1([Mg]Br)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.C1C[O:33][CH2:32]C1>C(OCC)(=O)C.O>[CH:22]1([C:20]2[N:21]=[C:32]([OH:33])[N:1]=[C:2]3[C:3]=2[N:4]=[CH:5][N:6]3[C:7]2[CH:8]=[C:9]([CH:16]=[CH:17][C:18]=2[CH3:19])[C:10]([NH:12][CH:13]2[CH2:14][CH2:15]2)=[O:11])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

6

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 58088961HCID 58088961, compoundHCID 178419651HCID 178419651, compound

Product 1

HCID 178425823HCID 178425823, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(5-amino-4-cyano-imidazol-1-yl)-N-cyclopropyl-4-methyl-benzamide (28 mg, 0.1 mmol, see Example 2A) in dry THF (5 ml) under nitrogen was added a 1 M solution of cyclohexylmagnesium bromide in THF (2M, 0.25 mL, 0.5 mmol) at room temperature. After the reaction of mixture was stirred at that temperature for 4 hours, 5 mL of water was added. The mixture was extracted with ethyl acetate (3×20 mL), washed with water and dried over MgSO4, and concentrated. The crude product was dissolved in 2 mL of methylene chloride. And then 1,1-carbonyldiimidazole (32 mg, 0.2 mmol) was added. After being stirred at room temperature for 1 hour, the mixture was diluted with 50 mL of ethyl acetate and water, and the ethyl acetate layer was separated, washed with water, brine and then dried over MgSO4. After filtration and concentration, the crude product was purified by preparatory HPLC to give a solid (22 mg, 57%). HPLC tR=1.94 min; MS m/z 392 [M+H]+.

Workup

  1. customAfter the reaction of mixture
  2. extractionThe mixture was extracted with ethyl acetate (3×20 mL)
  3. washwashed with water
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. dissolutionThe crude product was dissolved in 2 mL of methylene chloride
  7. stirringAfter being stirred at room temperature for 1 hour
  8. customthe ethyl acetate layer was separated
  9. washwashed with water, brine
  10. dry with materialdried over MgSO4
  11. filtrationAfter filtration and concentration
  12. customthe crude product was purified by preparatory HPLC

Sources & evidence

ORD record
ord-3dbcfd5363dc48d3ba9c7f6453daede6
Source dataset
uspto-grants-2009_08
Patent number
US07569571B2

Reaction notes

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