Propargyl alcohol → 2-amino-5-[4-(difluoromethoxy)phenyl]-5-[3-(3-hydroxyprop-1-yn-1-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one

HRID 30588Notes

Reaction equation

HRID 30588 reaction equation
[NH2:1][C:2]1[N:6]([CH3:7])[C:5](=[O:8])[C:4]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21](Br)[CH:20]=2)([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH:16]([F:18])[F:17])=[CH:11][CH:10]=2)[N:3]=1.[OH:26][CH2:27][C:28]#[CH:29]>N1CCCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[N:6]([CH3:7])[C:5](=[O:8])[C:4]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH:16]([F:18])[F:17])=[CH:11][CH:10]=2)([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:29]#[C:28][CH2:27][OH:26])[CH:20]=2)[N:3]=1

Participants

6

Reactant 2

HCID 7859Propargyl alcoholHCID 597903072-amino-4-(3-bromophenyl)-4-(4-(difluoromethoxy)phenyl)-1-methyl-1H-imidazol-5(4H)-one

Product 1

HCID 574359142-amino-5-[4-(difluoromethoxy)phenyl]-5-[3-(3-hydroxyprop-1-yn-1-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-oneYield 45%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 31268PyrrolidineSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 2-amino-5-(3-bromophenyl)-5-[4-(difluoromethoxy)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one (2.4 g, 5.85 mmol), 3-hydroxy-1-propyne (3.27 g, 58.5 mmol) and Pd(PPh3)4 (670 mg, 0.585 mmol) in pyrrolidine is heated at 70° C. under a nitrogen atmosphere for 16 h, diluted with water and extracted with CH2Cl2. The extracts are combined, dried over MgSO4 and concentrated in vacuo to give a residue. The residue is purified by chromatography on a silica cartridge, to give 2-amino-5-[4-(difluoromethoxy)phenyl]-5-[3-(3-hydroxyprop-1-yn-1-yl)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one, 1 g (45% yield), identified by NMR and mass spectral analyses.

Workup

  1. extractionextracted with CH2Cl2
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customto give a residue
  5. customThe residue is purified by chromatography on a silica cartridge

Sources & evidence

ORD record
ord-18078c8f373a4486931851394b764c44
Source dataset
uspto-grants-2008_09
Patent number
US07423158B2

Reaction notes

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