Ammonium Chloride → Methyl 2-(5-(3-((4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)(methyl)carbamoyl)-5-(trifluoromethyl)phenylthio)pentanamido)acetate

HRID 878371Notes

Reaction equation

HRID 878371 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]([CH3:36])[C:16]([C:18]2[CH:19]=[C:20]([S:28][CH2:29][CH2:30][CH2:31][CH2:32][C:33](O)=[O:34])[CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=2)=[O:17])=[C:4]([O:37][CH3:38])[CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[CH3:52][O:53][C:54](=[O:57])[CH2:55][NH2:56].CCN(C(C)C)C(C)C.[NH4+].[Cl-]>CN(C=O)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]([CH3:36])[C:16]([C:18]2[CH:19]=[C:20]([S:28][CH2:29][CH2:30][CH2:31][CH2:32][C:33]([NH:56][CH2:55][C:54]([O:53][CH3:52])=[O:57])=[O:34])[CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=2)=[O:17])=[C:4]([O:37][CH3:38])[CH:3]=1

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 122755Glycine methyl ester hydrochloride2×HCID 706635065-(3-{[4-(4-Fluoro-2-methoxy-phenyl)-6-methyl-pyridin-3-yl]-methyl-carbamoyl}-5-trifluoromethyl-phenylsulfanyl)-pentanoic acid

Product 1

HCID 70663180Methyl 2-(5-(3-((4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)(methyl)carbamoyl)-5-(trifluoromethyl)phenylthio)pentanamido)acetate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-(3-((4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)(methyl)carbamoyl)-5-(trifluoromethyl)phenylthio)pentanoic acid (0.15 g, 272 μmol, example 312) in DMF (1 mL) was added 1,1′-carbonyldiimidazole (66.3 mg, 409 μmol) and the clear solution was stirred at room temperature for 45 minutes before glycin methyl ester hydrochloride (37.6 mg, 300 μmol) was added. Reaction mixture was stirred at room temperature for 20.5 hours before DIPEA (35.2 mg, 47.6 μL, 272 μmol) and glycin methyl ester hydrochloride (37.6 mg, 300 μmol) was added. After 23 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 washed twice with water and once with brine, dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 20 g column using a MPLC system eluting with a gradient of CH2Cl2:MeOHe (100:0 to 90:10). Colorless foam (0.142 g; 79%). MS (ESI): m/z=622.20 [M+H]+.

Workup

  1. additionwas added
  2. customReaction mixture
  3. additionwas added
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted twice with EtOAc
  6. washThe organic layers were washed twice with water and once with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. additiontreated with silica gel
  10. customevaporated
  11. customThe compound was purified by silica gel chromatography on a 20 g column
  12. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-06a1508496014fb484c96a05ecc07b29
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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