(E)-6-methoxy-hex-1-enylboronic acid → 2-Amino-5-[4-(difluoromethoxy)phenyl]-5-{3-[(1E)-6-methoxy-hex-1-en-1-yl]-phenyl}-3-methyl-3,5-dihydro-4H-imidazol-4-one

HRID 30584Notes

Reaction equation

HRID 30584 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.[CH3:26][O:27][CH2:28][CH2:29][CH2:30][CH2:31]/[CH:32]=[CH:33]/B(O)O>C([O-])([O-])=O.[K+].[K+].COCCOC.O>[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](/[CH:33]=[CH:32]/[CH2:31][CH2:30][CH2:29][CH2:28][O:27][CH3:26])[CH:20]=2)[N:3]=1

Participants

6

Reactant 2

HCID 18386901(E)-6-methoxy-hex-1-enylboronic acidHCID 597903072-amino-4-(3-bromophenyl)-4-(4-(difluoromethoxy)phenyl)-1-methyl-1H-imidazol-5(4H)-one

Product 1

HCID 161144852-Amino-5-[4-(difluoromethoxy)phenyl]-5-{3-[(1E)-6-methoxy-hex-1-en-1-yl]-phenyl}-3-methyl-3,5-dihydro-4H-imidazol-4-oneYield 56%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 11430Potassium CarbonateSolvent

Conditions

Temperature
95 °C

Procedure

A degassed solution of 2-amino-5-(3-bromophenyl)-5-[4-(difluoromethoxy)phenyl]-3-methyl-3,5-dihydro-4H-imidazol-4-one (200 mg, 0.488 mmol) and (E)-6-methoxy-hex-1-enylboronic acid (0.537 mmol) in 1 ml of 2 M K2CO3 and 2.5 ml of DME is treated with Pd(CH3CN)2Cl2 (20 mg, 5%), the mixture heated at 95° 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. The resultant residue is purified on a silica gel cartridge and then by preparative HPLC to afford the title compound, 121 mg (56% yield), identified by NMR and mass spectral analyses. (1H-NMR 300 MHz, CDCl3): 7.49 (d, 2H); 7.42 (s br, 1H); 7.27 (m, 5H); 7.06 (d, 2H); 6.49 (dd, 1H); 6.36 (d, 1H); 6.20 (dt, 1H); 3.41 (t, 2H); 3.35 (s, 3H); 3.12 (s, 3H); 2.22 (dt, 2H); 1.69-1.47 (m, 4H). MS [M+H]+ 444.4

Workup

  1. extractionextracted with CH2Cl2
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe resultant residue is purified on a silica gel cartridge

Sources & evidence

ORD record
ord-01668d48446c440b9fb20a50a1aded35
Source dataset
uspto-grants-2008_09
Patent number
US07423158B2

Reaction notes

Loading…