1,2-Dichloroethane → methyl (S)-4-[1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-2-pyrrolidinylmethoxy]benzoate

HRID 350349Notes

Reaction equation

HRID 350349 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].[NH:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[CH2:29][O:30][C:31]1[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][CH:32]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CN(C1C=CN=CC=1)C.CN(C=O)C.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:20][C:21]([N:24]2[CH2:28][CH2:27][CH2:26][C@H:25]2[CH2:29][O:30][C:31]2[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][CH:32]=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

8

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 114498403-Methoxy-4-o-tolylureidophenylacetic acidHCID 16093581methyl (S)-4-(2-pyrrolidinylmethoxy)benzoate

Product 1

HCID 86587779methyl (S)-4-[1-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]-2-pyrrolidinylmethoxy]benzoateYield 75%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-methoxy4-[N′-(2-methylphenyl)ureido]phenylacetic acid (428 mg, 1.36 mmol), methyl (S)-4-(2-pyrrolidinylmethoxy)benzoate (330 mg, 1.40 mmol), EDC (312 mg, 1.63 mg), HOBt (220 mg, 1.63 mmol), and a catalytic amount of DMAP in DMF (15 mL) was stirred for 6 hr. The resulting mixture was diluted with EtOAc, washed with 0.5 N HCl, sat. NaHCO3, brine, and dried over MgSO4. The solvent was evaporated off in vacuo to give an oily residue, which was purified by column chromatography on silica-gel with CHCl3-MeOH (50:1, v/v) as eluent to give 540 mg (75%) methyl (S)-4-[1-[3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetyl]-2-pyrrolidinylmethoxy]benzoate as an oil. 1H-NMR (CDCl3) δ 1.81–2.12 (m, 4 H) 2.88 (bs, 3 H), 3.48–3.61 (m, total 7 H), 3.88 (s, 3 H), 4.10–4.21 (m, 2 H), 4.42–4.46 (m, 1 H), 6.75–8.08 (series of m, total 13 H).

Workup

  1. washwashed with 0.5 N HCl, sat. NaHCO3, brine
  2. dry with materialdried over MgSO4
  3. customThe solvent was evaporated off in vacuo
  4. customto give an oily residue, which
  5. customwas purified by column chromatography on silica-gel with CHCl3-MeOH (50:1

Sources & evidence

ORD record
ord-87a0c8d0b0d7496f8fac2759c47a259d
Source dataset
uspto-grants-2007_02
Patent number
US07179819B2

Reaction notes

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