5-Bromovaleric acid → HCID 70663181, compound

HRID 878279Notes

Reaction equation

HRID 878279 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH3:28])[C:15](=[O:27])[C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([SH:26])[CH:17]=2)=[C:4]([O:29][CH3:30])[CH:3]=1.Br[CH2:32][CH2:33][CH2:34][CH2:35][C:36]([OH:38])=[O:37].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]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH3:28])[C:15]([C:16]2[CH:17]=[C:18]([S:26][CH2:32][CH2:33][CH2:34][CH2:35][C:36]([OH:38])=[O:37])[CH:19]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=2)=[O:27])=[C:4]([O:29][CH3:30])[CH:3]=1

Participants

7

Reactant 4

HCID 163685-Bromovaleric acidHCID 25517Ammonium ChlorideHCID 81531Diisopropylethylamine2×HCID 70663556HCID 70663556, compound

Product 1

HCID 70663181HCID 70663181, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of N-(4-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)-3-mercapto-N-methyl-5-(trifluoromethyl)benzamide (0.115 g, 264 μmol, Example 216, intermediate a) in acetonitrile (2 mL) were added 5-bromopentanoic acid (59.6 mg, 329 μmol) and DIPEA (85.1 mg, 115 μL, 659 μmol). After the addition of DIPEA the white suspension turned to a light yellow solution, which was stirred at room temperature for 18 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 10 g column using an MPLC (Flashmaster) system eluting with a gradient of CH2Cl2:MeOH (100:0 to 0:0). The product was further 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 (0.10 g; 70%). MS (ESI): m/z=537.15 [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 10 g column
  8. washeluting with a gradient of CH2Cl2:MeOH (100:0 to 0:0)
  9. customThe product was further purified by preparative HPLC (Gemini NX column)

Sources & evidence

ORD record
ord-fcf87dbce0a94b21b74a602328f0885b
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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