Lithium Hydroxide → HCID 72190295, compound

HRID 531309Notes

Reaction equation

HRID 531309 reaction equation
[F:1][CH:2]1[CH2:5][N:4]([C:6]2[N:11]=[C:10]([CH2:12][N:13]3[C@@H:17]([CH3:18])[C@@H:16]([C:19]4[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[C:21]([F:29])[CH:20]=4)[O:15][C:14]3=[O:30])[C:9]([C:31]3[CH:32]=[C:33]([C:39]4[C:48]([CH3:49])=[CH:47][C:42]([C:43]([O:45]C)=[O:44])=[CH:41][C:40]=4[CH3:50])[CH:34]=[N:35][C:36]=3[O:37][CH3:38])=[CH:8][N:7]=2)[CH2:3]1.[OH-].[Li+].C(O)(C(F)(F)F)=O>O1CCOCC1>[F:1][CH:2]1[CH2:5][N:4]([C:6]2[N:11]=[C:10]([CH2:12][N:13]3[C@@H:17]([CH3:18])[C@@H:16]([C:19]4[CH:24]=[C:23]([C:25]([F:27])([F:26])[F:28])[CH:22]=[C:21]([F:29])[CH:20]=4)[O:15][C:14]3=[O:30])[C:9]([C:31]3[CH:32]=[C:33]([C:39]4[C:40]([CH3:50])=[CH:41][C:42]([C:43]([OH:45])=[O:44])=[CH:47][C:48]=4[CH3:49])[CH:34]=[N:35][C:36]=3[O:37][CH3:38])=[CH:8][N:7]=2)[CH2:3]1

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 6422Trifluoroacetic acidHCID 90009179HCID 90009179, compound

Product 1

HCID 72190295HCID 72190295, compoundYield 75.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of methyl 4-{5-[2-(3-fluoroazetidin-1-yl)-4-({(4S,5R)-5-[3-fluoro-5-(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3,5-dimethylbenzoate (Step A, 82 mg, 0.118 mmol) in dioxane (2.4 mL) was added an aqueous solution of lithium hydroxide (1.2 mL, 0.5 M). The mixture was heated at 60° C. for one hour. The reaction mixture was cooled and acidified by the addition of TFA (0.090 mL, 1.17 mmol). Volatiles were removed under reduced pressure and the residue was purified by preparative HPLC reverse phase (C-18) to give 4-{5-[2-(3-fluoroazetidin-1-yl)-4-({(4S,5R)-5-[3-fluoro-5-(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3,5-dimethylbenzoic acid (60.7 mg, 0.089 mmol) as a white solid following lyophilization. LCMS (M+H)+: 684.1. 1H NMR (500 MHz, CD3OD): δ 8.19 (s, 1H), 8.03 (s, 1H), 7.80 (s, 2H), 7.50 (m, 3H), 7.40 (m, 1H), 5.80 (d, 1H, J=8.4 Hz), 5.49 (br s, 0.5H), 5.42 (br s, 0.5H), 4.64 (d, 1H, J=16.9 Hz), 4.50 (m, 2H), 4.40 (m, 1H), 4.24 (m, 2H), 4.14 (d, 1H, J=16.9 Hz), 4.02 (s, 3H) 2.17 (s, 3H), 2.16 (s, 3H), 0.76 (d, 3H, J=6.6 Hz). RTA IC50: 15 nM.

Workup

  1. temperatureThe reaction mixture was cooled
  2. customVolatiles were removed under reduced pressure
  3. customthe residue was purified by preparative HPLC reverse phase (C-18)

Sources & evidence

ORD record
ord-5af03e6201854bb383120e4981d0d43f
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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