Sodium methanesulfinate → 2,2-dichloro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(6-((methylsulfonyl)methyl)pyridin-3-yl)phenyl)propan-2-yl)acetamide

HRID 1500275Notes

Reaction equation

HRID 1500275 reaction equation
[Cl:1][CH:2]([Cl:28])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[N:20][C:21]([CH2:24]Cl)=[CH:22][CH:23]=3)=[CH:14][CH:13]=2)[O:7]C1(C)C)=[O:4].[CH3:29][S:30]([O-:32])=[O:31].[Na+]>CN(C)C=O>[Cl:1][CH:2]([Cl:28])[C:3]([NH:5][C@H:9]([CH2:10][F:11])[C@H:8]([OH:7])[C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:19]=[N:20][C:21]([CH2:24][S:30]([CH3:29])(=[O:32])=[O:31])=[CH:22][CH:23]=2)=[CH:14][CH:13]=1)=[O:4]

Participants

4

Reactant 2

HCID 2733271Sodium methanesulfinateHCID 867131642,2-dichloro-1-((4S,5R)-5-(4-(6-(chloromethyl)pyridin-3-yl)phenyl)-4 (fluoromethyl)-2,2-dimethyloxazolidin-3-yl)ethanone

Product 1

HCID 867131652,2-dichloro-N-((1R,2S)-3-fluoro-1-hydroxy-1-(4-(6-((methylsulfonyl)methyl)pyridin-3-yl)phenyl)propan-2-yl)acetamideYield 34.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The product of step 2 (50 mg, 0.11 mmol) and sodium methanesulfinate (23 mg, 0.22 mmol) in dimethylformamide (1 mL) is heated at 60° C. for 1 hour. The solvent is removed under reduced pressure and DCM (1 mL) is added, followed by trifluoroacetic acid (0.25 mL). The reaction mixture is stirred at room temperature for 3 hours. The reaction mixture is diluted with toluene (5 mL) then the solvent removed under reduced pressure. The crude material is purified using HPLC (5 to 95 acetonitrile/water) to give title compound (17 mg): 1H NMR (400 MHz, DMSO-d6) δ:3.03 (s, 3H), 4.15-4.34 (m, 1.5H), 4.38-4.46 (m, 0.5H), 4.55-4.62 (m, 0.5H), 4.65-4.76(m, 2.5H), 4.89 (t, J=4.0 Hz, 1H), 6.00 (d, J=4.0 Hz, 1H), 6.53 (s, 1H), 7.49(d, J=8.0 Hz, 2H), 7.58 (d, J=8.0 Hz, 1H), 7.72 (d, J=8.0 Hz, 2H), 8.11-8.17 (m, 1H), 8.62 (d, J=8.0 Hz, 1H), 8.90 (bs, 1H). m/z (Cl) 449 [M+H].

Workup

  1. customThe solvent is removed under reduced pressure and DCM (1 mL)
  2. additionis added
  3. additionThe reaction mixture is diluted with toluene (5 mL)
  4. customthe solvent removed under reduced pressure
  5. customThe crude material is purified

Sources & evidence

ORD record
ord-a68fe6b239e2451a8e06622679fbed1f
Source dataset
uspto-grants-2015_12
Patent number
US09206126B2

Reaction notes

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