(RS)-N-(4-cyano-2-hydroxy-benzyl)-2-(2,6-difluoro-4-methoxy-phenyl)-2-ethoxy-acetamide → (RS)-N-{4-Carbamimidoyl-2-[(2-diethylamino-ethylcarbamoyl)-methoxy]-benzyl}-2-(2,6-difluoro-4-methoxy-phenyl)-2-ethoxy-acetamide hydrochloride

HRID 1247356Notes

Reaction equation

HRID 1247356 reaction equation
[C:1]([C:3]1[CH:26]=[CH:25][C:6]([CH2:7][NH:8][C:9](=[O:24])[CH:10]([C:14]2[C:19]([F:20])=[CH:18][C:17]([O:21][CH3:22])=[CH:16][C:15]=2[F:23])[O:11][CH2:12][CH3:13])=[C:5]([OH:27])[CH:4]=1)#[N:2].[Cl:28]CC1N=CO[N:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(C1C=C[C:46]([CH2:47][NH:48][C:49](=[O:64])[CH:50](C2C(F)=CC(OC)=CC=2F)OCC)=C(OCC2N=CON=2)C=1)#N.C(C1C=C[C:79]([CH2:80][NH:81][C:82](=O)[CH:83](C2C(F)=CC(OC)=CC=2F)OCC)=C(OCC#N)C=1)#N>CN(C=O)C>[ClH:28].[C:1]([C:3]1[CH:26]=[CH:25][C:6]([CH2:7][NH:8][C:9](=[O:24])[CH:10]([C:14]2[C:15]([F:23])=[CH:16][C:17]([O:21][CH3:22])=[CH:18][C:19]=2[F:20])[O:11][CH2:12][CH3:13])=[C:5]([O:27][CH2:50][C:49](=[O:64])[NH:48][CH2:47][CH2:46][N:81]([CH2:82][CH3:83])[CH2:80][CH3:79])[CH:4]=1)(=[NH:31])[NH2:2]

Participants

6

Reactant 4

HCID 21905119(RS)-N-(4-cyano-2-hydroxy-benzyl)-2-(2,6-difluoro-4-methoxy-phenyl)-2-ethoxy-acetamideHCID 21905564N-(4-cyano-2-cyanomethoxy-benzyl)-2-(2,6-difluoro-4-methoxy-phenyl)-2-ethoxy-acetamideHCID 21905736N-[4-cyano-2-([1,2,4]oxadiazol-3-ylmethoxy)-benzyl]-2-(2,6-difluoro-4-methoxy-phenyl)-2-ethoxy-acetamideHCID 865930463-(Chloromethyl)-1,2,4-oxadiazole cesium carbonate

Product 1

HCID 21905123(RS)-N-{4-Carbamimidoyl-2-[(2-diethylamino-ethylcarbamoyl)-methoxy]-benzyl}-2-(2,6-difluoro-4-methoxy-phenyl)-2-ethoxy-acetamide hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In analogy to example 16.4, (RS)-N-(4-cyano-2-hydroxy-benzyl)-2-(2,6-difluoro-4-methoxy-phenyl)-2-ethoxy-acetamide (example 126.1) was alkylated with 3-(chloromethyl)-1,2,4-oxadiazole/cesium carbonate in DMF to give a mixture of N-[4-cyano-2-([1,2,4]oxadiazol-3-ylmethoxy)-benzyl]-2-(2,6-difluoro-4-methoxy-phenyl)-2-ethoxy-acetamide and N-(4-cyano-2-cyanomethoxy-benzyl)-2-(2,6-difluoro-4-methoxy-phenyl)-2-ethoxy-acetamide. These compounds were converted according to general procedure D to give (RS)-N-{4-Carbamimidoyl-2-[(2-diethylamino-ethylcarbamoyl)-methoxy]-benzyl}-2-(2,6-difluoro-4-methoxy-phenyl)-2-ethoxy-acetamide hydrochloride.

Workup

  1. customto give

Sources & evidence

ORD record
ord-0e297f140a2541db9096d7befd85f23b
Source dataset
uspto-grants-2006_10
Patent number
US07129238B2

Reaction notes

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