Trifluoroacetic acid → 4-{5-[4-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(3,3-difluoroazetidin-1-yl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3-methylbenzoic acid

HRID 531299Notes

Reaction equation

HRID 531299 reaction equation
[F:1][C:2]([F:56])([F:55])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[CH:46]=[CH:45][C:37]([C:38]([O:40]C(C)(C)C)=[O:39])=[CH:36][C:35]=5[CH3:47])[CH:29]=[N:30][C:31]=4[O:32][CH3:33])=[CH:24][N:23]=[C:22]([N:48]4[CH2:51][C:50]([F:53])([F:52])[CH2:49]4)[N:21]=3)[C@H:14]2[CH3:54])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.FC(F)(F)C(O)=O>ClCCl>[F:12][C:9]([F:10])([F:11])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:26]4[CH:27]=[C:28]([C:34]5[CH:46]=[CH:45][C:37]([C:38]([OH:40])=[O:39])=[CH:36][C:35]=5[CH3:47])[CH:29]=[N:30][C:31]=4[O:32][CH3:33])=[CH:24][N:23]=[C:22]([N:48]4[CH2:49][C:50]([F:52])([F:53])[CH2:51]4)[N:21]=3)[C@H:14]2[CH3:54])[CH:4]=[C:3]([C:2]([F:56])([F:55])[F:1])[CH:8]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 124089233tert-Butyl 4-{5-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(3,3-difluoroazetidin-1-yl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3-methylbenzoate

Product 1

HCID 721896684-{5-[4-({(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(3,3-difluoroazetidin-1-yl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3-methylbenzoic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 4-{5-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(3,3-difluoroazetidin-1-yl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3-methylbenzoate (Step A, 639 mg, 0.805 mmol) was treated with 20 mL of a mixture of dichloromethane and trifluoroacetic acid (2 to 1 by volume) at room temperature for 0.5 hour, and purified on reverse phase HPLC to give the title compound as a white solid, after lyophilization. LCMS (M+H)+: 738.0. 1H NMR (CD3OD, 500 MHz): δ 8.26 (s, 1H), 8.22 (d, J=2.0 Hz, 1H), 8.00 (s, 1H), 7.96 (s, 1H), 7.93 (s, 2H), 7.90 (dd, J=1.5 Hz, 8.0 Hz, 1H), 7.71 (d, J=2.5 Hz, 1H), 7.38 (d, J=8.0 Hz, 1H), 5.87 (d, J=9.0 Hz, 1H), 4.69 (d, J=16.0 Hz, 1H), 4.45 (m, 4H), 4.43 (m, 1H), 4.15 (d, J=16.0 Hz, 1H), 4.00 (s, 3H), 2.38 (s, 3H), 0.73 (d, J=6.5 Hz, 3H). RTA IC50: 9 nM

Workup

  1. custompurified on reverse phase HPLC

Sources & evidence

ORD record
ord-15de505af88c41d4a5f29e45195e82fc
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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