2-(4-Fluorophenyl)acetyl isocyanate → 2-{[4-(Dimethylaminomethyl)piperidin-1-yl]carbonylamino}-4-(4-{3-[2-(4-fluorophenyl)acetyl]ureido}phenoxy)pyridine

HRID 492930Notes

Reaction equation

HRID 492930 reaction equation
[NH2:1][C:2]1[CH:27]=[CH:26][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]3[CH2:21][CH2:20][CH:19]([CH2:22][N:23]([CH3:25])[CH3:24])[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[CH:4][CH:3]=1.[F:28][C:29]1[CH:34]=[CH:33][C:32]([CH2:35][C:36]([N:38]=[C:39]=[O:40])=[O:37])=[CH:31][CH:30]=1>O1CCCC1>[CH3:25][N:23]([CH2:22][CH:19]1[CH2:20][CH2:21][N:16]([C:14]([NH:13][C:9]2[CH:8]=[C:7]([O:6][C:5]3[CH:26]=[CH:27][C:2]([NH:1][C:39]([NH:38][C:36](=[O:37])[CH2:35][C:32]4[CH:33]=[CH:34][C:29]([F:28])=[CH:30][CH:31]=4)=[O:40])=[CH:3][CH:4]=3)[CH:12]=[CH:11][N:10]=2)=[O:15])[CH2:17][CH2:18]1)[CH3:24]

Participants

4

Reactant 2

HCID 231530882-(4-Fluorophenyl)acetyl isocyanateHCID 231533224-(4-Aminophenoxy)-2-{[4-(dimethylaminomethyl)piperidin-1-yl]carbonylamino}pyridine

Product 1

HCID 231530442-{[4-(Dimethylaminomethyl)piperidin-1-yl]carbonylamino}-4-(4-{3-[2-(4-fluorophenyl)acetyl]ureido}phenoxy)pyridineYield 36%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-(4-aminophenoxy)-2-{[4-(dimethylaminomethyl)piperidin-1-yl]carbonylamino}pyridine (61.8 mg) in tetrahydrofuran (2.0 ml) was added a solution of 2-(4-fluorophenyl)acetyl isocyanate in tetrahydrofuran (0.25 M, 1.7 ml) at room temperature, followed by stirring for 3 days. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate) to provide the titled compound (32.6 mg, 36%) as white powder.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated
  5. customto give a residue, which
  6. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate)

Sources & evidence

ORD record
ord-4d6659731dda4033ab5dbd4c1881e57a
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

Loading…