3,5-Bis(trifluoromethyl)benzoic acid → {(3,5-Bis-trifluoromethyl-benzoyl)-[4-(4,5-difluoro-2-methoxy-phenyl)-pyridin-3-yl]-amino}-acetic acid methyl ester

HRID 878209Notes

Reaction equation

HRID 878209 reaction equation
[CH3:1][O:2][C:3](=[O:22])[CH2:4][NH:5][C:6]1[CH:7]=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([F:18])[C:15]([F:19])=[CH:14][C:13]=1[O:20][CH3:21].[F:23][C:24]([F:39])([F:38])[C:25]1[CH:26]=[C:27]([CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:33]=1)[C:28](O)=[O:29]>>[CH3:1][O:2][C:3](=[O:22])[CH2:4][N:5]([C:28](=[O:29])[C:27]1[CH:31]=[C:32]([C:34]([F:35])([F:36])[F:37])[CH:33]=[C:25]([C:24]([F:23])([F:38])[F:39])[CH:26]=1)[C:6]1[CH:7]=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([F:18])[C:15]([F:19])=[CH:14][C:13]=1[O:20][CH3:21]

Participants

3

Reactant 2

HCID 128893,5-Bis(trifluoromethyl)benzoic acidHCID 70663491[4-(4,5-Difluoro-2-methoxy-phenyl)-pyridin-3-ylamino]-acetic acid methyl ester

Product 1

HCID 86670786{(3,5-Bis-trifluoromethyl-benzoyl)-[4-(4,5-difluoro-2-methoxy-phenyl)-pyridin-3-yl]-amino}-acetic acid methyl ester

Procedure

The title compound was prepared in analogy to example 90, from [4-(4,5-difluoro-2-methoxy-phenyl)-pyridin-3-ylamino]-acetic acid methyl ester (example 172, intermediate a) and 3,5-bis(trifluoromethyl)benzoic acid (CAS RN 725-89-3) after a reaction time of 72 hours. The compound was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). The product-containing fractions were pooled and evaporated and the residue purified by preparative HPLC (Gemini NX column) using a gradient of methanol:water with 0.05% formic acid (80:20 to 98:2). Colorless solid (10%). MS (ESI): m/z=549.105 [M+H]+.

Workup

  1. customThe compound was purified by silica gel chromatography
  2. washeluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)
  3. customevaporated
  4. customthe residue purified by preparative HPLC (Gemini NX column)

Sources & evidence

ORD record
ord-528d4212ff954281a9a9437076c2873d
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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