methyl 4-[N-[1-[3-methoxy-4-[N'-(2-fluorophenyl)ureido]phenylacetyl]-2-pyrrolidinyl methyl]-N-methylamino]-3-nitrobenzoate → methyl 3-amino-4-[N-[1-[4-[N'-(2-fluorophenyl)ureido]-3-methoxy-phenylacetyl]-2-pyrrolidinylmethyl]-N-methylamino]benzoate

HRID 354334Notes

Reaction equation

HRID 354334 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:43])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([N:20]2[CH2:24][CH2:23][CH2:22][CH:21]2[CH2:25][N:26]([C:28]2[CH:37]=[CH:36][C:31]([C:32]([O:34][CH3:35])=[O:33])=[CH:30][C:29]=2[N+:38]([O-])=O)[CH3:27])=[O:19])=[CH:13][C:12]=1[O:41][CH3:42]>CO.[Pd]>[NH2:38][C:29]1[CH:30]=[C:31]([CH:36]=[CH:37][C:28]=1[N:26]([CH2:25][CH:21]1[CH2:22][CH2:23][CH2:24][N:20]1[C:18](=[O:19])[CH2:17][C:14]1[CH:15]=[CH:16][C:11]([NH:10][C:9]([NH:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])=[O:43])=[C:12]([O:41][CH3:42])[CH:13]=1)[CH3:27])[C:32]([O:34][CH3:35])=[O:33]

Participants

4

Reactant 1

HCID 69332166methyl 4-[N-[1-[3-methoxy-4-[N'-(2-fluorophenyl)ureido]phenylacetyl]-2-pyrrolidinyl methyl]-N-methylamino]-3-nitrobenzoate

Product 1

HCID 69333340methyl 3-amino-4-[N-[1-[4-[N'-(2-fluorophenyl)ureido]-3-methoxy-phenylacetyl]-2-pyrrolidinylmethyl]-N-methylamino]benzoateYield 48%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A stirred solution of methyl 4-[N-[1-[4-[N′-(2-fluorophenyl)ureido]-3-methoxyphenylacetyl]-2-pyrrolidinylmethyl]-N-methylamino]-3-nitrobenzoate (901.0 mg, 1.518 mmol) in MeOH (18.0 mL) was hydrogenated over 5%Pd-C (1.35 g) at 45 psi overnight. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was made basic with 1N NaOH solution and extracted with CHCl3. The extract was washed with brine, dried over Na2SO4, and the solvent was removed under a reduced pressure. The residue was chromatographed on silica-gel with CHCl3—MeOH (24:1, v/v) as eluent to afford 283.7 mg (48%) methyl 3-amino-4-[N-[1-[4-[N′-(2-fluorophenyl)ureido]-3-methoxy-phenylacetyl]-2-pyrrolidinylmethyl]-N-methylamino]benzoate as a brownish amorphous solid, which was used to the subsequent reaction without further purification.

Workup

  1. customat 45 psi overnight
  2. filtrationThe mixture was filtered
  3. concentrationthe filtrate was concentrated in vacuo
  4. extractionextracted with CHCl3
  5. washThe extract was washed with brine
  6. dry with materialdried over Na2SO4
  7. customthe solvent was removed under a reduced pressure
  8. customThe residue was chromatographed on silica-gel with CHCl3—MeOH (24:1

Sources & evidence

ORD record
ord-d3fcff968e8a4f46a5ed59efeac2869c
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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