Triethylamine → N-(2-((S)-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)ethyl)methanesulfonamide

HRID 2091521Notes

Reaction equation

HRID 2091521 reaction equation
[NH2:1][CH2:2][CH2:3][C@@:4]1([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH3:12])[CH2:6][CH2:5]1.C(N(CC)CC)C.[CH3:31][S:32](Cl)(=[O:34])=[O:33]>C(Cl)Cl>[CH3:15][C:13]([CH3:16])([CH3:14])[C@@H:11]([N:7]1[CH2:6][CH2:5][C@:4]([CH2:3][CH2:2][NH:1][S:32]([CH3:31])(=[O:34])=[O:33])([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[O:9][C:8]1=[O:10])[CH3:12]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 58485270(R)-6-(2-aminoethyl)-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one

Product 1

HCID 42642287N-(2-((S)-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)ethyl)methanesulfonamideYield 67.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-6-(2-aminoethyl)-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one (144 mg, 0.45 mmol) and triethylamine (136 mg, 1.35 mmol) in CH2Cl2 (5 mL) was added methanesulfonyl chloride (153 mg, 1.35 mmol) at 0° C., and the reaction mixture was stirred at rt until the reaction was over. The reaction was quenched with H2O. The mixture was extracted with EtOAc, and the organic phase was washed with brine, dried over Na2SO4, filtered and concentrated to give crude product, which was purified by preparative TLC to afford N-(2-((S)-3-((S)-3,3-dimethylbutan-2-yl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)ethyl)methanesulfonamide (121 mg, 67%). LC-MS Method 1 tR=1.192, min, m/z=401.1; 1H NMR (CDCl3): 0.65 (s, 9H), 1.01-1.07 (d, 3H), 1.96-2.06 (m, 1H), 2.12-2.18 (m, 2H), 2.21-2.28 (m, 1H), 2.57-2.66 (m, 1H), 2.78 (s, 3H), 2.85-2.97 (m, 1H), 3.01-3.12 (m, 2H), 4.31-4.39 (m, 1H), 4.64-4.72 (m, 1H), 6.98-7.07 (m, 2H), 7.19-7.24 (m, 2H).

Workup

  1. customThe reaction was quenched with H2O
  2. extractionThe mixture was extracted with EtOAc
  3. washthe organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give crude product, which
  8. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-42eade204b314d0facbf54423437404e
Source dataset
uspto-grants-2013_05
Patent number
US08440658B2

Reaction notes

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