Tetrahydrofuran → HCID 11501399, compound

HRID 2099229Notes

Reaction equation

HRID 2099229 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)[CH2:26][CH2:25][CH2:24][CH2:23]1.[CH2:29]1COCC1>>[CH:22]1([C:20]2[N:21]=[CH:29][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])[CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 58088961HCID 58088961, compoundHCID 178419650HCID 178419650, compound

Product 1

HCID 11501399HCID 11501399, compoundYield 23%

Procedure

To a stirred solution of 3-(5-amino-4-cyano-imidazol-1-yl)-N-cyclopropyl-4-methyl-benzamide (140 mg) in THF (25 mL, dry) under nitrogen at room temperature was added cyclopentylmagnesium bromide (2.5 mL, 2 M in diethyl ether). The mixture was stirred at room temperature for 3 hr before solvent was removed. The residue was redissolved in EtOAc, washed by water, brine, dried over Na2SO4, and concentrated. The residue was redissolved in MeOH (2.0 mL), HC(OMe)3 (2.0 mL) and TsOH (catalytic amount) were added. The mixture was irritated at 120° C. using microwave for 20 min. The solvent was removed and the crude product was purified by column chromatography on silica gel eluted with EtOAc, followed by further purifictaction by preparatory HPLC to give the title compound as a white solid (41.2 mg, 23%). HPLC tR=2.07 min; MS m/z 362.31 [M+H]+.

Workup

  1. customwas removed
  2. dissolutionThe residue was redissolved in EtOAc
  3. washwashed by water, brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. dissolutionThe residue was redissolved in MeOH (2.0 mL)
  7. additionHC(OMe)3 (2.0 mL) and TsOH (catalytic amount) were added
  8. customwas irritated at 120° C.
  9. customfor 20 min
  10. customThe solvent was removed
  11. customthe crude product was purified by column chromatography on silica gel
  12. washeluted with EtOAc

Sources & evidence

ORD record
ord-929ac851fb3d48059709150587e989ec
Source dataset
uspto-grants-2009_08
Patent number
US07569571B2

Reaction notes

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