Phenylacetyl isocyanate → 4-[2-(Azetidin-1-yl)ethyl]piperazine-1-carboxylic acid {4-[4-(3-phenylacetylureido)phenoxy]pyridin-2-yl}amide

HRID 492991Notes

Reaction equation

HRID 492991 reaction equation
[NH2:1][C:2]1[CH:29]=[CH:28][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][N:19]([CH2:22][CH2:23][N:24]4[CH2:27][CH2:26][CH2:25]4)[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[CH:4][CH:3]=1.[C:30]1([CH2:36][C:37]([N:39]=[C:40]=[O:41])=[O:38])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>CN(C)C=O.CCCCCC.C(OCC)C>[C:30]1([CH2:36][C:37]([NH:39][C:40](=[O:41])[NH:1][C:2]2[CH:3]=[CH:4][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]4[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][N:24]5[CH2:27][CH2:26][CH2:25]5)[CH2:18][CH2:17]4)=[O:15])[CH:8]=3)=[CH:28][CH:29]=2)=[O:38])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

6

Reactant 2

HCID 12259960Phenylacetyl isocyanateHCID 576775264-[2-(Azetidin-1-yl)ethyl]piperazine-1-carboxylic acid [4-(4-aminophenoxy)pyridin-2-yl]amide

Product 1

HCID 576776074-[2-(Azetidin-1-yl)ethyl]piperazine-1-carboxylic acid {4-[4-(3-phenylacetylureido)phenoxy]pyridin-2-yl}amideYield 56%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolvent2×

Procedure

To a solution of 4-[2-(azetidin-1-yl) ethyl]piperazine-1-carboxylic acid [4-(4-aminophenoxy)pyridin-2-yl]amide (36.3 mg) in N,N-dimethylformamide (1 ml) was added a solution of 0.25 M 2-phenylacetyl isocyanate in hexane (1.1 ml) under a nitrogen atmosphere, followed by stirring for 1 hr. The reaction mixture was partitioned between ethyl acetate (100 ml) and a saturated aqueous solution of sodium hydrogencarbonate (50 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (50 ml), water (50 ml), brine (50 ml) 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, then ethyl acetate:methanol=9:1). Fractions containing the target compound were concentrated to give a residue, which was then suspended in diethyl ether (3.0 ml) and hexane (1.5 ml). The solid was filtered off and dried under aeration to provide the titled compound (28.6 mg, 56.0%) as white powder.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate (100 ml)
  2. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (50 ml), water (50 ml), brine (50 ml)
  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
  7. additionFractions containing the target compound
  8. concentrationwere concentrated
  9. customto give a residue, which
  10. filtrationThe solid was filtered off
  11. customdried under aeration

Sources & evidence

ORD record
ord-2845d03f2f2940b797d17d09a6e2e5f4
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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