Hippuric Acid → 3-(2-(4-methoxybenzylamino)-6-(2-methyl-1H-imidazol-1-yl)quinolin-3-yl)-N-(cyclohexylmethyl)propanamide

HRID 930222Notes

Reaction equation

HRID 930222 reaction equation
[CH3:1][O:2][C:3]1[CH:33]=[CH:32][C:6]([CH2:7][NH:8][C:9]2[C:18]([CH2:19][CH2:20][C:21]([NH:23][CH2:24][CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)=[O:22])=[CH:17][C:16]3[C:11](=[CH:12][CH:13]=[C:14](Br)[CH:15]=3)[N:10]=2)=[CH:5][CH:4]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:40](O)(=O)[CH2:41][NH:42][C:43]([C:45]1C=CC=CC=1)=O.C[N:54](C=O)C>O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:1][O:2][C:3]1[CH:33]=[CH:32][C:6]([CH2:7][NH:8][C:9]2[C:18]([CH2:19][CH2:20][C:21]([NH:23][CH2:24][CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)=[O:22])=[CH:17][C:16]3[C:11](=[CH:12][CH:13]=[C:14]([N:54]4[CH:40]=[CH:41][N:42]=[C:43]4[CH3:45])[CH:15]=3)[N:10]=2)=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 464Hippuric AcidHCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 711385863-(2-(4-methoxybenzylamino)-6-bromoquinolin-3-yl)-N-(cyclohexylmethyl)propanamide

Product 1

HCID 711384843-(2-(4-methoxybenzylamino)-6-(2-methyl-1H-imidazol-1-yl)quinolin-3-yl)-N-(cyclohexylmethyl)propanamide

Reagents, catalysts & solvents 1

HCID 165397Cupric acetate monohydrateCatalyst

Conditions

Temperature
140 °C

Procedure

In a sealed tube was combined 3-(2-(4-methoxybenzylamino)-6-bromoquinolin-3-yl)-N-(cyclohexylmethyl)propanamide (0.32 g, 0.63 mmol, prepared as in Example 5), copper (II) acetate monohydrate (0.025 g, 0.13 mmol), cesium carbonate (0.61 g, 1.9 mmol), hippuric acid (0.016 ml, 0.13 mmol), 2-methyl-/H-imidazole (0.062 g, 0.75 mmol) and DMF (5 mL). The tube was sealed and heated to 140° C. for 48 h. The mixture was cooled to RT, transferred to a flask and concentrated to remove the DMF. Adsorbtion onto silica and purification via flash chromatography (slow gradient, 2-10% MeOH/DCM) provided 3-(2-(4-methoxybenzylamino)-6-(2-methyl-1H-imidazol-1-yl) quinolin-3-yl)-N-(cyclohexylmethyl)propanamide (representative compound 13). Step 2 A solution of 3-(2-(4-methoxybenzylamino)-6-(2-methyl-1H-imidazol-1-yl)quinolin-3-yl)-N-(cyclohexylmethyl)propanamide in TFA (10 mL) was heated at 45° C. for 30 min until complete by LC/MS. After concentrating under reduced pressure to remove the TFA, the oil was dissolved in MeOH and purified by reverse phase HPLC to afford 3-(2-amino-6-(2-methyl-1H-imidazol-1-yl)quinolin-3-yl)-N-(cyclohexylmethyl)propanamide (representative compound 6). MS (ESI, pos. ion) m/z: 392 (M+1).

Workup

  1. customIn a sealed tube was combined
  2. customThe tube was sealed
  3. temperatureThe mixture was cooled to RT
  4. customtransferred to a flask
  5. concentrationconcentrated
  6. customto remove the DMF
  7. customAdsorbtion onto silica and purification via flash chromatography (slow gradient, 2-10% MeOH/DCM)

Sources & evidence

ORD record
ord-a7342f854b4f47ba8c0bf734806324da
Source dataset
uspto-grants-2016_03
Patent number
US09296698B2

Reaction notes

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