Triethylamine → methyl 4-[(2S,4S)-1-[4-[N'-(2-chlorophenyl)ureido]-3-methoxyphenylacetyl]-4-methoxy-2-pyrrolidinyl]methoxybenzoate

HRID 354431Notes

Reaction equation

HRID 354431 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:23])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([OH:20])=O)=[CH:13][C:12]=1[O:21][CH3:22].[CH3:24][O:25][C@@H:26]1[CH2:30][NH:29][C@H:28]([CH2:31][O:32][C:33]2[CH:42]=[CH:41][C:36]([C:37]([O:39][CH3:40])=[O:38])=[CH:35][CH:34]=2)[CH2:27]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:23])[NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]([N:29]2[CH2:30][C@@H:26]([O:25][CH3:24])[CH2:27][C@H:28]2[CH2:31][O:32][C:33]2[CH:42]=[CH:41][C:36]([C:37]([O:39][CH3:40])=[O:38])=[CH:35][CH:34]=2)=[O:20])=[CH:13][C:12]=1[O:21][CH3:22]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 16093585HCID 16093585, compoundHCID 235118674-[N'-(2-chlorophenyl)ureido]-3-methoxyphenylacetic acid

Product 1

HCID 69333168methyl 4-[(2S,4S)-1-[4-[N'-(2-chlorophenyl)ureido]-3-methoxyphenylacetyl]-4-methoxy-2-pyrrolidinyl]methoxybenzoateYield 87%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-[N′-(2-chlorophenyl)ureido]-3-methoxyphenylacetic acid (398 mg, 1.19 mmol), methyl 4-[(2S,4S)-4-methoxy-2-pyrrolidinyl]methoxybenzoate (317 mg, 1.19 mmol), EDC.HCl (342 mg, 1.79 mmol), HOBT (242 mg, 1.79 mmol) and Et3N (0.83 ml, 5.95 mmol) in DMF (5 ml) was stirred at room temperature for 13 h. 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 [50 g, CHCl3/Aectone (10/1)CHCl3/MeOH (20/1)], to give methyl 4-[(2S,4S)-1-[4-[N′-(2-chlorophenyl)ureido]-3-methoxyphenylacetyl]-4-methoxy-2-pyrrolidinyl]methoxybenzoate (600 mg, 87%) as a colorless amorphous solid 1H-NMR (CDCl3) δ1.99-2.06 (m, 1H), 2.34 (d, J=13.9 Hz, 1H), 3.30 (s, 3H), 3.59 (d, J=7.4 Hz, 1H), 3.62 (d, J=3.2 Hz, 2H), 3.83 (s, 3H), 3.88 (s, 3H), 4.00-4.18 (m, 3H), 4.42-4.51 (m, 2H), 6.82-7.07 (m, 7H), 7.28 (d, J=8.3 Hz, 1H), 7.35 (dd, J=7.9, 1.5 Hz, 1H), 7.94-8.00 (m, 3H), 8.18 (d, J=8.3 Hz, 1H); MS (ESI) m/z 582 (M++1), 5.84 (M++3).

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 [50 g, CHCl3/Aectone (10/1)CHCl3/MeOH (20/1)]

Sources & evidence

ORD record
ord-ac815539ccac477391628d29e8ed8bbf
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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