Trifluoroacetic acid → 2-cyano-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(6-(methylsulfonamidomethyl)pyridin-3-yl)phenyl)propan-2-yl)acetamide

HRID 525604Notes

Reaction equation

HRID 525604 reaction equation
[F:1][CH2:2][C@@H:3]1[C@@H:7]([C:8]2[CH:13]=[CH:12][C:11]([Sn](C)(C)C)=[CH:10][CH:9]=2)[O:6]C(C)(C)[N:4]1[C:20](=[O:24])[CH2:21][C:22]#[N:23].Br[C:26]1[CH:27]=[CH:28][C:29]([CH2:32][NH:33][S:34]([CH3:37])(=[O:36])=[O:35])=[N:30][CH:31]=1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.FC(F)(F)C(O)=O>CN(C)C=O.O.C(Cl)Cl.C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:22]([CH2:21][C:20]([NH:4][C@H:3]([CH2:2][F:1])[C@H:7]([OH:6])[C:8]1[CH:9]=[CH:10][C:11]([C:26]2[CH:31]=[N:30][C:29]([CH2:32][NH:33][S:34]([CH3:37])(=[O:35])=[O:36])=[CH:28][CH:27]=2)=[CH:12][CH:13]=1)=[O:24])#[N:23]

Participants

10

Reactant 4

HCID 6422Trifluoroacetic acidHCID 521585Tris(furan-2-yl)phosphaneHCID 67819070N-((5-bromopyridin-2-yl)methyl)methanesulfonamideHCID 866954953-((4S,5R)-4-(fluoromethyl)-2,2-dimethyl-5-(4-(trimethylstannyl)-phenyl)oxazolidin-3-yl)-3-oxopropanenitrile

Product 1

HCID 866954942-cyano-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(6-(methylsulfonamidomethyl)pyridin-3-yl)phenyl)propan-2-yl)acetamideYield 2.8%

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 3-((4S,5R)-4-(fluoromethyl)-2,2-dimethyl-5-(4-(trimethylstannyl)-phenyl)oxazolidin-3-yl)-3-oxopropanenitrile (150 mg, 0.342 mmol), N-((5-bromopyridin-2-yl)methyl) methanesulfonamide (90 mg, 0.342 mmol), tris(2-furyl)phosphine (16 mg, 0.068 mmol) and tris(dibenzylideneacetone)dipalladium(0) (32 mg, 0.034 mmol) in dimethylformamide (3 mL) is heated at 70° C. for 4 h under nitrogen. The mixture is then cooled, diluted with water (10 mL) and extracted with ethyl acetate (3×15 mL). Extracts are dried over Na2SO4 and concentrated to get crude product m/z (Cl) M+H 461. Obtained product is dissolved in CH2Cl2 (3 mL) and treated with trifluoroacetic acid (0.5 mL) for 3 hours at room temperature. Reaction is diluted with toluene (10 mL) and concentrated to syrup. Obtained crude product dissolved in dimethylformamide (2 mL) and purified using HPLC to give the title product (4 mg): m/z (Cl) M+H 421.

Workup

  1. temperatureThe mixture is then cooled
  2. extractionextracted with ethyl acetate (3×15 mL)
  3. dry with materialExtracts are dried over Na2SO4
  4. concentrationconcentrated
  5. customto get crude product m/z (Cl) M+H 461
  6. customReaction
  7. concentrationconcentrated to syrup
  8. customObtained crude product
  9. custompurified

Sources & evidence

ORD record
ord-0d935ad0895849f5b4a5df3b1f65de3d
Source dataset
uspto-grants-2016_05
Patent number
US09340564B2

Reaction notes

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