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

HRID 492962Notes

Reaction equation

HRID 492962 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][CH:19]([CH2:22][N:23]4[CH2:27][CH2:26][CH2:25][CH2:24]4)[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[C:4](F)[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>CN(C)C=O.CCCCCC.C(OCC)C>[C:31]1([CH2:37][C:38]([NH:40][C:41](=[O:42])[NH:1][C:2]2[CH:29]=[CH:28][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][CH:19]([CH2:22][N:23]5[CH2:27][CH2:26][CH2:25][CH2:24]5)[CH2:18][CH2:17]4)=[O:15])[CH:8]=3)=[CH:4][CH:3]=2)=[O:39])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

6

Reactant 2

HCID 12259960Phenylacetyl isocyanateHCID 866021744-(Pyrrolidin-1-ylmethyl)piperidine-1-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide

Product 1

HCID 576774764-(Pyrrolidin-1-ylmethyl)piperidine-1-carboxylic acid {4-[4-(3-phenylacetylureido)phenoxy]pyridin-2-yl}amide

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8058HexaneSolvent2×

Procedure

4-(Pyrrolidin-1-ylmethyl)piperidine-1-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide (50 mg) was dissolved in N,N-dimethylformamide (1.5 ml) under a nitrogen atmosphere, and then 0.25 M 2-phenylacetyl isocyanate in hexane (1.45 ml) was added, followed by stirring for 64.5 hrs. 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) and brine (50 ml) in this order, 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). Fractions containing the target compound were concentrated to give a residue, which was then suspended in diethyl ether (3 ml) and hexane (3 ml). The solid was filtered off, and dried under aeration to provide the titled compound (49.1 mg) 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) and brine (50 ml) in this order
  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)
  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-1b3ec174edda43e2a1fcd321c2fffe1d
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

Loading…