1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → methyl 4-[(2S,4S)-1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-4-(2-naphthyloxy)-2-pyrrolidinyl]methoxybenzoate

HRID 354411Notes

Reaction equation

HRID 354411 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:20][C:21]([OH:23])=O)[CH:6]=[CH:7][C:8]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19])=[O:11].[CH:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][C:25]=1[O:34][C@@H:35]1[CH2:39][NH:38][C@H:37]([CH2:40][O:41][C:42]2[CH:51]=[CH:50][C:45]([C:46]([O:48][CH3:49])=[O:47])=[CH:44][CH:43]=2)[CH2:36]1.CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:20][C:21]([N:38]2[CH2:39][C@@H:35]([O:34][C:25]3[CH:26]=[CH:27][C:28]4[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=4)[CH:24]=3)[CH2:36][C@H:37]2[CH2:40][O:41][C:42]2[CH:43]=[CH:44][C:45]([C:46]([O:48][CH3:49])=[O:47])=[CH:50][CH:51]=2)=[O:23])[CH:6]=[CH:7][C:8]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19])=[O:11]

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 114498403-Methoxy-4-o-tolylureidophenylacetic acidHCID 16093586methyl 4-((2S,4S)-4-(2-naphthyloxy)-2-pyrrolidinylmethoxy)benzoate

Product 1

HCID 69333210methyl 4-[(2S,4S)-1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-4-(2-naphthyloxy)-2-pyrrolidinyl]methoxybenzoateYield 728.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetic acid (333 mg, 0.106 mmol), methyl 4-[(2S,4S)-4-(2-naphthyloxy)-2-pyrrolidinyl]methoxybenzoate (400 mg, 1.06 mmol), EDC.HCl (305 mg, 1.59 mmol) and DMAP (194 mg, 1.59 mmol) in DMF (10 ml) was stirred at room temperature for 3 days. The mixture was poured into ice water and extracted with EtOAc. The combined extracts were washed with ice water and brine. After dried over Na2SO4, the extracts were concentrated in vacuo. The residue was chromatographed on silica gel [100 g, n-hexane/EtOAc(1/1)CHCl3/MeOH(50/1)], to give methyl 4-[(2S,4S)-1-[3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetyl]-4-(2-naphthyloxy)-2-pyrrolidinyl]methoxybenzoate (520 mg, 73%) as a pale brown amorphous. 1H-NMR (CDCl3) δ2.28 (s, 3H), 2.29 (m, 1H), 2.55 (d, J=14.2 Hz, 1H), 3.60 (d, J=3.4 Hz, 2H), 3.66 (d, J=3.7 Hz, 3H), 3.68-4.00 (m, 5H), 4.05-4.67 (m, 3H), 5.09 (br, 1H), 6.61 (s, 1H), 6.77 (m, 2H), 6.87 (d, J=8.8 Hz, 1H), 6.94-7.54 (m, 8H), 7.68-8.09 (m, 8H); MS (ESI) m/z 674 (M++1).

Workup

  1. extractionextracted with EtOAc
  2. washThe combined extracts were washed with ice water and brine
  3. dry with materialAfter dried over Na2SO4
  4. concentrationthe extracts were concentrated in vacuo
  5. customThe residue was chromatographed on silica gel [100 g, n-hexane/EtOAc(1/1)CHCl3/MeOH(50/1)]

Sources & evidence

ORD record
ord-95fa76c9f3ed4bed96d168b8266b382e
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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