1,2-Dichloroethane → HCID 178426471, compound

HRID 1874900Notes

Reaction equation

HRID 1874900 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([F:20])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([CH3:19])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.[Br:21][C:22]1[N:23]=[C:24]([CH3:30])[NH:25][C:26]=1[C:27](O)=[O:28].CCN(C(C)C)C(C)C.C(Cl)CCl>C1COCC1>[Br:21][C:22]1[N:23]=[C:24]([CH3:30])[NH:25][C:26]=1[C:27]([NH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[C:5]([O:10][C:11]2[CH:18]=[C:17]([CH3:19])[CH:16]=[C:13]([C:14]#[N:15])[CH:12]=2)[C:4]=1[F:20])=[O:28]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 684881693-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-methylbenzonitrileHCID 1784324484-bromo-2-methyl-1H-imidazole-5-carboxylic acid

Product 1

HCID 178426471HCID 178426471, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-methylbenzonitrile (0.046 g, 0.158 mmol), 4-bromo-2-methyl-1H-imidazole-5-carboxylic acid (0.032 g, 0.158 mmol) and DIEA (0.055 mL, 0.316 mmol) were combined in THF (3 mL) and treated with EDC (0.061 g, 0.316 mmol) at 25° C. overnight with stirring. The reaction mixture was concentrated to dryness and partitioned between EtOAc and water. The organic phase was isolated, dried over MgSO4, filtered and concentrated to dryness. The residue was purified on 40 g silica gel eluted with 0 to 10% CH3OH/DCM to give 4-bromo-N-({4-chloro-3-[(3-cyano-5-methylphenyl)oxy]-2-fluorophenyl}methyl)-2-methyl-1H-imidazole-5-carboxamide (0.052 g, 0.109 mmol, 68.8% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6+1 drop D2O) δ ppm 7.38-7.49 (m, 2H), 7.31 (t, J=7.90 Hz, 1H), 7.15 (m, 1H), 7.11 (s, 1H), 4.47 (s, 2H), 2.31 (s, 3H), 2.24 (s, 3 H). LC-MS (ES−) m/z 475.07, 477.03, 479.03 [M−1]. LC-MS (ES+) m/z 477.11, 479.09, 481.07 [M+H].

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. custompartitioned between EtOAc and water
  3. customThe organic phase was isolated
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe residue was purified on 40 g silica gel
  8. washeluted with 0 to 10% CH3OH/DCM

Sources & evidence

ORD record
ord-6d9505c4a9a247d99b64441b04a61ccd
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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