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 354334노트

반응식

HRID 354334 반응식
[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]

참가 물질

4

반응물 1

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

생성물 1

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

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 887Methanol용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-d3fcff968e8a4f46a5ed59efeac2869c
출처 데이터셋
uspto-grants-2004_06
특허 번호
US06756378B2

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