Water → HCID 20737836, compound

HRID 354445Notes

Reaction equation

HRID 354445 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.[Br:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[NH:31][C:32](=[O:45])[NH:33][C:34]1[CH:39]=[CH:38][C:37]([CH2:40][C:41](O)=[O:42])=[CH:36][C:35]=1[CH3:44].CCN=C=NCCCN(C)C.Cl.O>CN(C=O)C>[Br:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[NH:31][C:32](=[O:45])[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[CH3:44]

Participants

6

Reactant 4

HCID 962WaterHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23511815HCID 23511815, compoundHCID 69332954methyl 4-[5-(R)-phenyl-2-(S)-pirrolidinylmethoxy]benzate

Product 1

HCID 20737836HCID 20737836, compoundYield 90.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of methyl 4-[5-(R)-phenyl-2-(S)-pirrolidinylmethoxy]benzoate (125 mg, 0.40 mmol), 4-[N′-(2-bromophenyl)ureido]-3-methylphenylacetic acid (146 mg, 0.40 mmol) and N,N-dimethylaminopyridine (49.0 mg, 0.40 mmol) in DMF (10 ml) was added EDC.HCl (84.1 mg, 0.44 mmol) at rt, and the resulting mixture was stirred for 6 h. 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 (1:4) as eluent to give methyl 4-[1-[4-[N′-(2-bromophenyl)ureido]-3-methylphenylacetyl]-5-(R)-phenyl-2-(S)-pyrrolidinylmethoxy]benzoate (238 mg, 90%) as a colorless amorphous solid. 1H-NMR (CDCl3) δ1.92 (s, 3 H), 2.09-2.27 (m, 3 H), 2.42-2.50 (m, 1 H), 3.22-3.41 (m, 2 H), 3.88 (s, 3 H), 4.39 (d, J=4.4 Hz, 1 H), 4.64 (brs, 1 H), 5.00 (t, J=6.8 Hz, 1 H), 6.72 (s, 1 H), 6.81-6.93 (series of m, 8 H), 7.22-7.42 (series of m, 6 H), 8.01 (d, J=8.4 Hz, 2 H), 8.13 (d, J=8.0 Hz, 1 H ); MS (FAB) m/z, 656 (M+), 658 (M++2).

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 (1:4) as eluent

Sources & evidence

ORD record
ord-2c26f16da411449ab632b29b2178a938
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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