1-Hydroxybenzotriazole → methyl (S)-3-chloro-4-[2-[N-methyl-N-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]amino]-1-propoxy]benzoate

HRID 354498Notes

Reaction equation

HRID 354498 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].[Cl:24][C:25]1[CH:26]=[C:27]([CH:32]=[CH:33][C:34]=1[O:35][CH2:36][C@@H:37]([NH:39][CH3:40])[CH3:38])[C:28]([O:30][CH3:31])=[O:29].C1C=CC2N(O)N=NC=2C=1>CN(C1C=CN=CC=1)C.CN(C=O)C.CCOC(C)=O>[Cl:24][C:25]1[CH:26]=[C:27]([CH:32]=[CH:33][C:34]=1[O:35][CH2:36][C@@H:37]([N:39]([CH3:40])[C:21](=[O:23])[CH2:20][C:5]1[CH:6]=[CH:7][C:8]([NH:9][C:10]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:19])=[O:11])=[C:3]([O:2][CH3:1])[CH:4]=1)[CH3:38])[C:28]([O:30][CH3:31])=[O:29]

Participants

7

Reactant 3

HCID 757711-HydroxybenzotriazoleHCID 114498403-Methoxy-4-o-tolylureidophenylacetic acidHCID 86587798methyl (S)-3-chloro-4-(2-methylamino-1-propoxy)benzoate

Product 1

HCID 86595082methyl (S)-3-chloro-4-[2-[N-methyl-N-[3-methoxy-4-[N'-(2-methylphenyl)ureido]phenylacetyl]amino]-1-propoxy]benzoateYield 102.2%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of 3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetic acid (261 mg, 0.83 mmol), methyl (S)-3-chloro-4-(2-methylamino-1-propoxy)benzoate (214 mg, 0.83 mmol), EDC(hydrochloride) (239 mg, 1.25 mmol), HOBt (168 mg, 1.24 mmol), and DMAP (20 mg, 0.16 mmol) in DMF (8 mL) was stirred at room temp for 2 hr. The mixture was diluted with EtOAc, washed with 0.5 N HCl, brine, dried over Na2SO4 and evaporated. The residue was purified by column chromatography on silica-gel with CHCl3—MeOH (50:1, v/v) as eluent to give 470 mg (100%) methyl (S)-3-chloro-4-[2-[N-methyl-N-[3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetyl]amino]-1-propoxy]benzoate as a pale yellow amorphous solid.

Workup

  1. washwashed with 0.5 N HCl, brine
  2. dry with materialdried over Na2SO4
  3. customevaporated
  4. customThe residue was purified by column chromatography on silica-gel with CHCl3—MeOH (50:1

Sources & evidence

ORD record
ord-66a9d3dc92eb4105b2eb1569e2392738
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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