Trifluoroacetic acid → HCID 72189977, compound

HRID 531307Notes

Reaction equation

HRID 531307 reaction equation
[F:1][C:2]1([F:53])[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[CH:51]=[CH:50][C:42]([C:43]([O:45]C(C)(C)C)=[O:44])=[CH:41][C:40]=4[CH3:52])[CH:34]=[N:35][C:36]=3[O:37][CH3:38])=[CH:8][N:7]=2)[CH2:3]1.C(O)(C(F)(F)F)=O>ClCCl>[F:53][C:2]1([F: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[CH:51]=[CH:50][C:42]([C:43]([OH:45])=[O:44])=[CH:41][C:40]=4[CH3:52])[CH:34]=[N:35][C:36]=3[O:37][CH3:38])=[CH:8][N:7]=2)[CH2:3]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90009210HCID 90009210, compound

Product 1

HCID 72189977HCID 72189977, compoundYield 47.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-{5-[2-(3,3-difluoroazetidin-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-methylbenzoate (Step A, 98 mg, 0.132 mmol) in dichloromethane (0.700 mL), cooled to 0° C. was added TFA (0.700 mL). The ice bath was removed and the reaction mixture was stirred for 1 hour. Upon completion the solvent was removed under reduced pressure and the resultant residue was dissolved in acetonitrile:water (1:1) for direct purification by reverse phase HPLC (C18) followed by lyophilization of appropriate fractions to yield 4-{5-[2-(3,3-difluoroazetidin-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-methylbenzoic acid (50.4 mg, 0.063 mmol) as a white fluffy solid. LCMS (M+H)+: 688.1. 1H NMR (500 MHz, CD3OD) δ8.27 (s, 1H), 8.23 (s, 1H), 7.97 (s, 1H), 7.91 (d, 1H, J=7.8 Hz), 7.71 (s, 1H), 7.50 (m, 2H), 7.39 (m, 2H), 5.76 (d, 1H, J=8.6 Hz), 4.67 (d, 1H, J=17.0 Hz), 4.53 (m, 4H), 4.38 (m, 1H), 4.16 (d, 1H, J=17.0 Hz), 4.01 (s, 3H), 2.39 (s, 3H), 0.75 (d, 3H, J=6.5 Hz). RTA IC50: 9 nM.

Workup

  1. customThe ice bath was removed
  2. customUpon completion the solvent was removed under reduced pressure
  3. dissolutionthe resultant residue was dissolved in acetonitrile:water (1:1) for direct purification by reverse phase HPLC (C18)

Sources & evidence

ORD record
ord-284a4a8e48fa481d988d675d1510ae66
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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