Diiodomethane → 2-Amino-5-[4-(difluoromethoxy)phenyl]-5-{3-[2-(methoxymethyl)-cyclopropyl]phenyl}-3-methyl-3,5-dihydro-4H-imidazol-4-one

HRID 30586

Reaction equation

HRID 30586 reaction equation
[CH2:1]([Zn]CC)C.C(C(O)=O)(F)(F)F.C(I)I.[NH2:16][C:17]1[N:21]([CH3:22])[C:20](=[O:23])[C:19]([C:35]2[CH:40]=[CH:39][C:38]([O:41][CH:42]([F:44])[F:43])=[CH:37][CH:36]=2)([C:24]2[CH:29]=[CH:28][CH:27]=[C:26](/[CH:30]=[CH:31]/[CH2:32][O:33][CH3:34])[CH:25]=2)[N:18]=1>C(Cl)Cl>[NH2:16][C:17]1[N:21]([CH3:22])[C:20](=[O:23])[C:19]([C:35]2[CH:36]=[CH:37][C:38]([O:41][CH:42]([F:44])[F:43])=[CH:39][CH:40]=2)([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([CH:30]3[CH2:1][CH:31]3[CH2:32][O:33][CH3:34])[CH:25]=2)[N:18]=1

Participants

6

Reactant 4

HCID 6346DiiodomethaneHCID 6422Trifluoroacetic acidHCID 161145862-amino-5-[4-(difluoromethoxy)phenyl]-5-{3-[(1E)-3-methoxyprop-1-en-1-yl]phenyl}-3-methyl-3,5-dihydro-4H-imidazol-4-oneHCID 178418750HCID 178418750, compound

Product 1

HCID 161145842-Amino-5-[4-(difluoromethoxy)phenyl]-5-{3-[2-(methoxymethyl)-cyclopropyl]phenyl}-3-methyl-3,5-dihydro-4H-imidazol-4-oneYield 16%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent4×

Procedure

A 1M solution of diethyl zinc (4.92 ml, 4.92 mmol) in dry CH2Cl2 at 0° C. is treated very slowly with a solution of CF3CO2H (0.56 g, 4.92 mmol) in dry CH2Cl2, stirred for 20 min, treated dropwise with a solution of CH2I2 (0.66 g, 2.46 mmol) in dry CH2Cl2, stirred for 20 min, treated with a solution of 2-amino-5-[4-(difluoromethoxy)phenyl]-5-{3-[(1E)-3-methoxyprop-1-en-1-yl]phenyl}-3-methyl-3,5-dihydro-4H-imidazol-4-one (197 mg, 0.492 mmol) in dry CH2Cl2, allowed to come to room temperature, stirred for 2 h at room temperature, quenched with aqueous NH4Cl and extracted with CH2Cl2. The combined extracts are dried over MgSO4 and concentrated in vacuo. The resultant residue is purified by SCX cartridge and preparative HPLC to give the title compound as a white solid, 32 mg (16% yield), identified by NMR and mass spectral analyses. (1H-NMR 300 MHz, DMSO): 7.46(d, 2H); 7.24-7.13(m, 3H); 7.16(t, 1H); 7.10(d, 2H); 6.88(m, 1H); 6.64(s br, 2H); 3.44-3.34(m, 2H); 3.24(m, 1H); 3.23(s, 3H); 2.97(s, 3H); 1.76(m, 1H); 0.90-0.76(m, 2H). MS [M+H]+ 416.1

Workup

  1. stirringstirred for 20 min
  2. customto come to room temperature
  3. stirringstirred for 2 h at room temperature
  4. customquenched with aqueous NH4Cl
  5. extractionextracted with CH2Cl2
  6. dry with materialThe combined extracts are dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe resultant residue is purified by SCX cartridge and preparative HPLC

Sources & evidence

ORD record
ord-a0c17451ec69485d91300d7732655d82
Source dataset
uspto-grants-2008_09
Patent number
US07423158B2

Linked notes

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