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 354334Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 354334
[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]

Komponenten

4

Edukt 1

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 23938PalladiumKatalysatorHCID 887MethanolLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-d3fcff968e8a4f46a5ed59efeac2869c
Quelldatensatz
uspto-grants-2004_06
Patentnummer
US06756378B2

Notizen zur Reaktion

Wird geladen…