Trifluoroacetic acid → HCID 72189976, compound

HRID 531305Notes

Reaction equation

HRID 531305 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[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: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[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 118021859HCID 118021859, compound

Product 1

HCID 72189976HCID 72189976, compoundYield 59.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 0° C. solution of tert-butyl 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-methylbenzoate (Step A, 95 mg, 0.131 mmol) in dichloromethane (0.700 mL) 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-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-methylbenzoic acid (62 mg, 0.078 mmol) as a white fluffy solid. LCMS (M+H)+: 670.2. 1H NMR (500 MHz, CD3OD): δ 8.22 (m, 2H), 7.98 (s, 1H), 7.91 (d, 1H, J=8.7 Hz), 7.70 (s, 1H), 7.50 (m, 2H), 7.40 (m, 2H), 5.76 (d, 1H, J=8.7 Hz), 5.54 (br s, 0.5H), 5.43 (br s, 0.5H), 4.62 (d, 1H, J=17.1 Hz), 4.50 (m, 2H), 4.40 (m, 1H), 4.24 (m, 2H), 4.14 (d, 1H, J=17.0 Hz), 4.02 (s, 3H), 2.39 (s, 3H), 0.75 (d, 3H, J=6.5 Hz). RTA IC50: 12 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-1f5a259b9b88434cbcfca16be1a57cd4
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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