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

HRID 354497Notes

Reaction equation

HRID 354497 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]([NH:13][C:14]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[F:23])=[O:15])[C:10]([OH:12])=O)[CH:6]=[CH:7][CH:8]=1.[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].C(Cl)CCl.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:10](=[O:12])[CH:9]([NH:13][C:14]([NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[F:23])=[O:15])[C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=1)[CH3:38])[C:28]([O:30][CH3:31])=[O:29]

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 698204933-methoxy-[N'-(2-fluorophenyl)ureido]phenylacetic acidHCID 86587798methyl (S)-3-chloro-4-(2-methylamino-1-propoxy)benzoate

Product 1

HCID 86587797methyl (S)-3-chloro-4-[2-[N-methyl-N-[3-methoxy-[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-[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-[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-f7cc9b8ba626427eb2a18da97491029c
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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