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

HRID 492981Notes

Reaction equation

HRID 492981 reaction equation
[NH2:1][C:2]1[CH:28]=[CH:27][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]4[CH2:26][CH2:25][CH2:24]4)[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[CH:4][CH:3]=1.[C:29]1([CH2:35][C:36]([N:38]=[C:39]=[O:40])=[O:37])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>CN(C)C=O.CCCCCC.C(OCC)C>[C:29]1([CH2:35][C:36]([NH:38][C:39](=[O:40])[NH:1][C:2]2[CH:28]=[CH:27][C:5]([O:6][C:7]3[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]4[CH2:17][CH2:18][CH:19]([CH2:22][N:23]5[CH2:26][CH2:25][CH2:24]5)[CH2:20][CH2:21]4)=[O:15])[CH:8]=3)=[CH:4][CH:3]=2)=[O:37])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

6

Reactant 2

HCID 12259960Phenylacetyl isocyanateHCID 866021774-(Azetidin-1-ylmethyl)piperidine-1-carboxylic acid [4-(4-aminophenoxy)pyridin-2-yl]amide

Product 1

HCID 576776344-(Azetidin-1-ylmethyl)piperidine-1-carboxylic acid {4-[4-(3-phenylacetylureido)phenoxy]pyridin-2-yl}amideYield 63.1%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolvent2×

Procedure

To a solution of 4-(azetidin-1-ylmethyl)piperidine-1-carboxylic acid [4-(4-aminophenoxy)pyridin-2-yl]amide (31 mg) in N,N-dimethylformamide (1 ml) was added a solution of 0.25 M 2-phenylacetyl isocyanate in hexane (0.982 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 (1.5 ml) and hexane (3 ml). The solid was filtered off and dried under aeration to provide the titled compound (28.0 mg, 63.1%) 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-4f648431e2b3413092f5e169b671c128
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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