Phenylacetyl isocyanate → 1-[1-(2-Dimethylaminoethyl)piperidin-4-yl]-1-methyl-3-{4-[4-(3-phenylacetylureido)phenoxy]pyridin-2-yl}urea

HRID 492973Notes

Reaction equation

HRID 492973 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14](=[O:28])[N:15]([CH:17]3[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][N:25]([CH3:27])[CH3:26])[CH2:19][CH2:18]3)[CH3:16])[CH:8]=2)=[CH:4][CH:3]=1.[C:31]1([CH2:37][C:38]([N:40]=[C:41]=[O:42])=[O:39])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>O1CCCC1.CCCCCC>[CH3:27][N:25]([CH3:26])[CH2:24][CH2:23][N:20]1[CH2:21][CH2:22][CH:17]([N:15]([CH3:16])[C:14]([NH:13][C:9]2[CH:8]=[C:7]([O:6][C:5]3[CH:4]=[CH:3][C:2]([NH:1][C:41]([NH:40][C:38](=[O:39])[CH2:37][C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=4)=[O:42])=[CH:30][CH:29]=3)[CH:12]=[CH:11][N:10]=2)=[O:28])[CH2:18][CH2:19]1

Participants

5

Reactant 2

HCID 12259960Phenylacetyl isocyanate2×HCID 231531743-[4-(4-Aminophenoxy)pyridin-2-yl]-1-[1-(2-dimethylaminoethyl)piperidin-4-yl]-1-methylurea

Product 1

HCID 576773431-[1-(2-Dimethylaminoethyl)piperidin-4-yl]-1-methyl-3-{4-[4-(3-phenylacetylureido)phenoxy]pyridin-2-yl}ureaYield 48%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent2×

Procedure

To a solution of 3-[4-(4-aminophenoxy)pyridin-2-yl]-1-[1-(2-dimethylaminoethyl)piperidin-4-yl]-1-methylurea (96 mg) in tetrahydrofuran (10 ml) was added a solution of 2-phenylacetyl isocyanate in hexane (0.25 M, 2.33 ml), followed by stirring at room temperature for 2.5 hrs. A solution of 2-phenylacetyl isocyanate in hexane (0.25 M, 0.800 ml) was added to the reaction mixture, followed by stirring at room temperature for 30 min. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, and dried over anhydrous sodium sulfate. The organic layer was concentrated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate:methanol=100:7). Fractions containing a target compound were concentrated to provide the titled compound (64.5 mg, 48%) as pale yellow powder.

Workup

  1. stirringby stirring at room temperature for 30 min
  2. customThe reaction mixture was partitioned between ethyl acetate
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationThe organic layer was concentrated
  7. customto give a residue, which
  8. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate:methanol=100:7)
  9. additionFractions containing a target compound
  10. concentrationwere concentrated

Sources & evidence

ORD record
ord-f3f6ae9bd6f94c47ab2030cc345fa698
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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