Lithium Chloride → 2,2-dichloro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(6-(methylsulfonamidomethyl)pyridin-3-yl)phenyl)propan-2-yl)acetamide

HRID 1520439Notes

Reaction equation

HRID 1520439 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][NH:9][S:10]([CH3:13])(=[O:12])=[O:11])=[N:6][CH:7]=1.[Cl:14][CH:15]([Cl:34])[C:16]([NH:18][C@H:19]([CH2:32][F:33])[C@H:20]([OH:31])[C:21]1[CH:26]=[CH:25][C:24]([Sn](C)(C)C)=[CH:23][CH:22]=1)=[O:17].[Cl-].[Li+]>>[Cl:14][CH:15]([Cl:34])[C:16]([NH:18][C@H:19]([CH2:32][F:33])[C@H:20]([OH:31])[C:21]1[CH:22]=[CH:23][C:24]([C:2]2[CH:7]=[N:6][C:5]([CH2:8][NH:9][S:10]([CH3:13])(=[O:12])=[O:11])=[CH:4][CH:3]=2)=[CH:25][CH:26]=1)=[O:17]

Participants

4

Reactant 3

HCID 433294Lithium ChlorideHCID 67819070N-((5-bromopyridin-2-yl)methyl)methanesulfonamideHCID 866953832,2-Dichloro-N-[(1S,2R)-1-fluoromethyl-2-hydroxy-2-(4-trimethylstannanyl-phenyl)-ethyl]-acetamide

Product 1

HCID 866953882,2-dichloro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(6-(methylsulfonamidomethyl)pyridin-3-yl)phenyl)propan-2-yl)acetamide

Conditions

Temperature
100 °C

Procedure

N-((5-bromopyridin-2-yl)methyl)methanesulfonamide (previously described in WO9528400) (240 mg, 0.90 mmol) and 2,2-dichloro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(trimethylstannyl)phenyl)propan-2-yl)acetamide (400 mg, 0.90 mmol) in 2-methylpyrrolidinone (5 mL) are treated with lithium chloride (115 mg, 2.7 mmol) and degassed and purged with nitrogen. Bis(triphenylphosphine)-palladium(ii) chloride is added and the mixture heated at 100° C. for 3 hours. The mixture is cooled, diluted with water and extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered, concentrated and purified by reverse phase chromatography to give the title compound (324 mg): 1H NMR (400 MHz, CDCl3) δ: 2.96 (s, 3H), 4.2-4.3 (m, 3H), 4.4 (m, 0.5H), 4.57 (m, 0.5H), 4.58 (m, 0.5H), 4.70 (m, 0.5H), 4.90 (bs, 1H), 6.00 (s, 1H), 6.52 (s, 1H), 7.47 (d, 2H), 7.52, (d, 1H), 7.69 (d, 3H), 8.1 (m, 1H), 8.85 (m, 1H), 8.82 (bs, 1H). m/z (Cl) 464.

Workup

  1. customdegassed
  2. custompurged with nitrogen
  3. additionBis(triphenylphosphine)-palladium(ii) chloride is added
  4. temperatureThe mixture is cooled
  5. additiondiluted with water
  6. extractionextracted with ethyl acetate
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by reverse phase chromatography

Sources & evidence

ORD record
ord-9f0987149e054b2fb5eb4e7444930452
Source dataset
uspto-grants-2015_07
Patent number
US09073894B2

Reaction notes

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