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

HRID 930255Notes

Reaction equation

HRID 930255 reaction equation
COC1C=CC(C[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:31]4[CH:35]=[CH:34][N:33]=[C:32]4[CH3:36])[CH:15]=3)[N:10]=2)=CC=1>C(O)(C(F)(F)F)=O>[NH2:8][C:9]1[C:18]([CH2:19][CH2:20][C:21]([NH:23][CH2:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[O:22])=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([N:31]3[CH:35]=[CH:34][N:33]=[C:32]3[CH3:36])[CH:15]=2)[N:10]=1

Participants

3

Reactant 1

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

Product 1

HCID 665812703-(2-amino-6-(2-methyl-1H-imidazol-1-yl)quinolin-3-yl)-N-(cyclohexylmethyl)propanamide

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

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 3), 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 room temperature, 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. 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. MS (ESI, pos. ion) m/z: 392 (M+1).

Workup

  1. concentrationAfter concentrating under reduced pressure
  2. customto remove the TFA
  3. dissolutionthe oil was dissolved in MeOH
  4. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-cfc9824020b34c3898164f454da7ff6d
Source dataset
uspto-grants-2016_03
Patent number
US09296698B2

Reaction notes

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