Water → HCID 20737843, compound

HRID 354442Notes

Reaction equation

HRID 354442 reaction equation
[C:1]1([C@@H:7]2[NH:11][C@H:10]([CH2:12][O:13][C:14]3[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[NH:31][C:32](=[O:46])[NH:33][C:34]1[CH:39]=[CH:38][C:37]([CH2:40][C:41](O)=[O:42])=[CH:36][C:35]=1[O:44][CH3:45].CCN=C=NCCCN(C)C.Cl.O>CN(C=O)C>[CH3:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[NH:31][C:32](=[O:46])[NH:33][C:34]1[CH:39]=[CH:38][C:37]([CH2:40][C:41]([N:11]2[C@@H:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:8][CH2:9][C@H:10]2[CH2:12][O:13][C:14]2[CH:15]=[CH:16][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:22][CH:23]=2)=[O:42])=[CH:36][C:35]=1[O:44][CH3:45]

Participants

6

Reactant 4

HCID 962WaterHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 114498403-Methoxy-4-o-tolylureidophenylacetic acidHCID 69332954methyl 4-[5-(R)-phenyl-2-(S)-pirrolidinylmethoxy]benzate

Product 1

HCID 20737843HCID 20737843, compoundYield 103.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of methyl 4-[5-(R)-phenyl-2-(S)-pirrolidinylmethoxy]benzoate (135 mg, 0.43 mmol), 4-[N′-(2-methylphenyl)ureido]-3-methoxyphenylacetic acid (136 mg, 0.43 mmol) and N,N-dimethylaminopyridine (52.9 mg, 0.43 mmol) in DMF (10 ml) was added EDC.HCl (90.8 mg, 0.48 mmol) at rt, and the resulting mixture was stirred overnight. The reaction mixture was poured into water and extracted with EtOAc. The organic layer was washed with brine, drying over anhydrous Na2SO4, then concentrated in vacuo. The residue was chromatographed on silica gel with hexane-EtOAc (1:5) as eluent to give methyl 4-[1-[4-[N′-(2-methylphenyl)ureido]-3-methoxyphenylacetyl]-5-(R)-phenyl-2-(S)-pyrrolidinylmethoxy]benzoate (271 mg, quant.) as a colorless amorphous solid. 1H-NMR (CDCl3) δ2.00-2.18 (m, 3 H), 2.31-2.41 (m, 1 H), 2.27 (s, 3 H), 3.31 (s, 2 H), 3.67 (s, 3 H), 3.89 (s, 3 H), 4.35-4.48 (m, 2 H), 4.60 (brs, 1 H), 4.92 (t, J=6.8 Hz, 1 H), 6.51 (d, J=8.4 Hz, 1 H), 6.62 (s, 1 H), 6.96 (d, J=8.8 Hz, 1 H), 7.11-7.40 (series of m, 8 H), 7.51 (d, J=8.0 Hz, 1 H), 7.97-8.00 (m, 2 H); MS (ESI) m/z, 608 (M++H).

Workup

  1. extractionextracted with EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdrying over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was chromatographed on silica gel with hexane-EtOAc (1:5) as eluent

Sources & evidence

ORD record
ord-8c0a7275276d4312b81a3f5573d37991
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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