Methanol → (R)-3-{[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-3-thiophen-2-yl-propionic acid methyl ester

HRID 1625465Notes

Reaction equation

HRID 1625465 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[F:29])[CH2:5][N:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([NH:14][C@@H:15]([C:20]2[S:21][CH:22]=[CH:23][CH:24]=2)[CH2:16][C:17]([OH:19])=[O:18])=[O:13])[C:7]1=[O:25].[CH3:30]O.S(Cl)(Cl)=O>C(Cl)Cl>[CH3:30][O:18][C:17](=[O:19])[CH2:16][C@@H:15]([NH:14][C:12]([C:8]1[C:7](=[O:25])[N:6]([CH2:5][C:4]2[CH:26]=[CH:27][C:28]([F:29])=[C:2]([F:1])[CH:3]=2)[CH:11]=[CH:10][CH:9]=1)=[O:13])[C:20]1[S:21][CH:22]=[CH:23][CH:24]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 68607579(R)-3-(1-(3,4-difluorobenzyl)-2-oxo-1,2-dihydropyridine-3-carboxamido)-3-(thiophen-2-yl)propanoic acid

Product 1

HCID 68606760(R)-3-{[1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carbonyl]-amino}-3-thiophen-2-yl-propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(R)-3-(1-(3,4-difluorobenzyl)-2-oxo-1,2-dihydropyridine-3-carboxamido)-3-(thiophen-2-yl)propanoic acid (0.631 g, 0.00151 mol;) was dissolved in Methanol (10 mL, 0.2 mol;) and cooled to 0 C. Thionyl chloride (600 uL, 0.008 mol;) was then added and the reaction was allowed to warm up o/n. LC-MS showed the formation of product at 1.63 432.97. The reaction was diluted with methylene chloride then washed 1× with sodium bicarbonate and 1× with brine before drying and concentration. The reaction was then concentrated and dissolved in methylene chloride for purification by combiflash using a 0-100 hexanes/ethyl acetate gradient. ES (+) MS m/e=432.97

Workup

  1. temperaturecooled to 0 C
  2. temperatureto warm up o/n
  3. washthen washed 1× with sodium bicarbonate and 1× with brine
  4. custombefore drying
  5. concentrationconcentration
  6. concentrationThe reaction was then concentrated
  7. dissolutiondissolved in methylene chloride for purification by combiflash

Sources & evidence

ORD record
ord-1ba176be27fb4b43bdcb4542afb95361
Source dataset
uspto-grants-2014_07
Patent number
US08778977B2

Reaction notes

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