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

HRID 350558Notes

Reaction equation

HRID 350558 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[F: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[F: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 23511825HCID 23511825, compoundHCID 86587798methyl (S)-3-chloro-4-(2-methylamino-1-propoxy)benzoate

Product 1

HCID 86595081methyl (S)-3-chloro-4-[2-[N-methyl-N-[3-methoxy-4-[N'-(2-fluorophenyl)ureido]phenylacetyl]amino]-1-propoxy]benzoateYield 100.2%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of 3-methoxy-4-[N′-(2-fluorophenyl)ureido]phenylacetic acid (296 mg, 0.93 mmol), methyl (S)-3-chloro-4-(2-methylamino-1-propoxy)benzoate (240 mg, 0.93 mmol), EDC(hydrochloride) (268 mg, 1.40 mmol), HOBt (189 mg, 1.40 mmol), and DMAP (23 mg, 0.19 mmol) in DMF (8 mL) was stirred at room temp for 1.5 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 5% MeOH in CHCl3 as eluent to give 520 mg (100%) methyl (S)-3-chloro-4-[2-[N-methyl-N-[3-methoxy-4-[N′-(2-fluorophenyl)ureido]phenylacetyl]amino]-1-propoxy]benzoate as a red-brown 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 5% MeOH in CHCl3 as eluent

Sources & evidence

ORD record
ord-3fe6e967b07249088dbc7fefe96e78ad
Source dataset
uspto-grants-2007_02
Patent number
US07179819B2

Reaction notes

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