5-Bromovaleric acid → 5-(3-{[4-(4-Fluoro-2-methoxy-phenyl)-6-methyl-pyridin-3-yl]-methyl-carbamoyl}-5-trifluoromethyl-phenylsulfanyl)-pentanoic acid

HRID 878367Notes

Reaction equation

HRID 878367 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10][C:9]=2[N:15]([CH3:29])[C:16](=[O:28])[C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([SH:27])[CH:18]=2)=[C:4]([O:30][CH3:31])[CH:3]=1.Br[CH2:33][CH2:34][CH2:35][CH2:36][C:37]([OH:39])=[O:38].CCN(C(C)C)C(C)C.[NH4+].[Cl-]>C(#N)C.CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10][C:9]=2[N:15]([CH3:29])[C:16]([C:17]2[CH:18]=[C:19]([S:27][CH2:33][CH2:34][CH2:35][CH2:36][C:37]([OH:39])=[O:38])[CH:20]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:22]=2)=[O:28])=[C:4]([O:30][CH3:31])[CH:3]=1

Participants

7

Reactant 4

HCID 163685-Bromovaleric acidHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 70663671N-(4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)-3-mercapto-N-methyl-5-(trifluoromethyl)benzamide

Product 1

HCID 706635065-(3-{[4-(4-Fluoro-2-methoxy-phenyl)-6-methyl-pyridin-3-yl]-methyl-carbamoyl}-5-trifluoromethyl-phenylsulfanyl)-pentanoic acid

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)-3-mercapto-N-methyl-5-(trifluoromethyl)benzamide (0.263 g, 584 μmol, example 310, intermediate a) in acetonitrile (4 mL) were added 5-bromopentanoic acid (132 mg, 730 μmol) and DIPEA (189 mg, 255 μL, 1.46 mmol) and the clear, light yellow solution was stirred at room temperature for 2.25 hours. The reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 20 g column using an MPLC system eluting with a gradient of CH2Cl2:MeOH (100:0 to 50:50). The product was purified by preparative HPLC (Gemini NX column) using a gradient of MeOH:water (containing 0.1% formic acid) (20:80 to 98:2). Colorless solid (0.119 g, 74%). MS (ESI): m/z=551.16 [M+H]+.

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted twice with EtOAc
  3. dry with materialThe organic layers were dried over MgSO4
  4. filtrationfiltered
  5. additiontreated with silica gel
  6. customevaporated
  7. customThe compound was purified by silica gel chromatography on a 20 g column
  8. washeluting with a gradient of CH2Cl2:MeOH (100:0 to 50:50)
  9. customThe product was purified by preparative HPLC (Gemini NX column)

Sources & evidence

ORD record
ord-e652ec6625e24a3aac857232b42b70ff
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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