Diisopropylethylamine → 2-(4-{2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetylamino}-3-fluoro-phenoxy)-2-methyl-propionic acid ethyl ester

HRID 1161342Notes

Reaction equation

HRID 1161342 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)[C:14]([NH:16][CH2:17][C@H:18]3CC[C@H](C(O)=O)C[CH2:19]3)=[O:15])[C:11]3[CH:33]=[CH:34][C:35]([F:37])=[CH:36][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.[F:38][P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C.[CH2:71]([O:73][C:74](=[O:87])[C:75]([O:78][C:79]1C=CC(N)=[C:81]([F:86])[CH:80]=1)([CH3:77])[CH3:76])[CH3:72]>CN(C)C=O.C(OCC)(=O)C>[CH2:71]([O:73][C:74](=[O:87])[C:75]([O:78][C:79]1[CH:19]=[CH:18][C:17]([NH:16][C:14](=[O:15])[CH:13]([N:12]2[C:11]3[CH:33]=[C:34]([F:38])[C:35]([F:37])=[CH:36][C:10]=3[N:9]=[C:8]2[C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)=[C:81]([F:86])[CH:80]=1)([CH3:77])[CH3:76])[CH3:72]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 671309762-(4-Amino-3-fluoro-phenoxy)-2-methyl-propionic acid ethyl esterHCID 178523387HCID 178523387, compound2×

Product 1

HCID 686460602-(4-{2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetylamino}-3-fluoro-phenoxy)-2-methyl-propionic acid ethyl esterYield 40%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the solution of 0.2 g (0.49 mmol) [2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexyl-acetic acid (example 22, intermediate c)) in 3 ml N,N-dimethylformamide, 0.21 g (0.55 mmol) O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate, 0.42 ml (0.32 g, 2.5 mmol) N-ethyldiisopropylamine and 0.13 g (0.54 mmol) 2-(4-amino-3-fluoro-phenoxy)-2-methyl-propionic acid ethyl ester were added. After 18 h the reaction mixture was poured on water and ethyl acetate, the phases were separated, the organic layer was washed twice with water followed by brine and dried over magnesium sulfate. After filtration the residue was purified by column chromatography on silica gel to give 0.12 g (40%) of the desired compound as light yellow foam.

Workup

  1. customthe phases were separated
  2. washthe organic layer was washed twice with water
  3. dry with materialdried over magnesium sulfate
  4. filtrationAfter filtration the residue
  5. customwas purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-10c6f0bbb8ab4367a0ce48505b93e9ea
Source dataset
uspto-grants-2010_10
Patent number
US07816540B2

Reaction notes

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