Hydrochloric Acid → (4S,5R)-3-{[5-(5-Chloro-2-methoxypyridin-3-yl)-2-(3-fluoroazetidin-1-yl)pyrimidin-4-yl]methyl}-4-methyl-5-[3-(trifluoromethoxy)phenyl]-1,3-oxazolidin-2-one

HRID 531236Notes

Reaction equation

HRID 531236 reaction equation
C(N(CC)CC)C.[Cl:8][C:9]1[CH:10]=[C:11]([C:17]2[C:18]([CH2:27][N:28]3[C@@H:32]([CH3:33])[C@@H:31]([C:34]4[CH:39]=[CH:38][CH:37]=[C:36]([O:40][C:41]([F:44])([F:43])[F:42])[CH:35]=4)[O:30][C:29]3=[O:45])=[N:19][C:20](S(C)(=O)=O)=[N:21][CH:22]=2)[C:12]([O:15][CH3:16])=[N:13][CH:14]=1.Cl.[F:47][CH:48]1[CH2:51][NH:50][CH2:49]1.Cl>C(OCC)(=O)C.C1COCC1>[Cl:8][C:9]1[CH:10]=[C:11]([C:17]2[C:18]([CH2:27][N:28]3[C@@H:32]([CH3:33])[C@@H:31]([C:34]4[CH:39]=[CH:38][CH:37]=[C:36]([O:40][C:41]([F:44])([F:43])[F:42])[CH:35]=4)[O:30][C:29]3=[O:45])=[N:19][C:20]([N:50]3[CH2:51][CH:48]([F:47])[CH2:49]3)=[N:21][CH:22]=2)[C:12]([O:15][CH3:16])=[N:13][CH:14]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 101250543-fluoroazetidine HydrochlorideHCID 90009163(4S,5R)-3-{[5-(5-Chloro-2-methoxypyridin-3-yl)-2-(methylsulfonyl)pyrimidin-4-yl]methyl}-4-methyl-5-[3-(trifluoromethoxy)phenyl]-1,3-oxazolidin-2-one

Product 1

HCID 90009161(4S,5R)-3-{[5-(5-Chloro-2-methoxypyridin-3-yl)-2-(3-fluoroazetidin-1-yl)pyrimidin-4-yl]methyl}-4-methyl-5-[3-(trifluoromethoxy)phenyl]-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

Triethylamine (0.499 mL, 3.58 mmol) was added to a THF (5 mL) solution of (4S,5R)-3-{[5-(5-chloro-2-methoxypyridin-3-yl)-2-(methylsulfonyl)pyrimidin-4-yl]methyl}-4-methyl-5-[3-(trifluoromethoxy)phenyl]-1,3-oxazolidin-2-one (Step A, 410 mg, 0.716 mmol) and 3-fluoroazetidine hydrochloride (300 mg, 2.69 mmol). The reaction was placed in an oil bath and heated for 20 minutes at 60° C. LCMS showed complete conversion to product. The reaction was diluted with ethyl acetate (50 mL) and poured into 0.1N HCl solution (50 mL). The ethyl acetate layer was washed with brine (50 mL), dried over sodium sulfate, filtered and the filtrate was concentrated on rotary evaporator. The crude isolate was purified by silica gel chromatography, eluting with a 0-50% ethyl acetate/hexanes linear gradient followed by a hold at 50% ethyl acetate/hexanes to give the title compound as a pale yellow solid. LCMS (M+H)+: 568.3. 1H NMR (500 MHz, CDCl3): δ 8.21 (d, J=2.3 Hz, 1H), 8.14 (s, 1H), 7.50 (d, J=2.4 Hz, 1H), 7.46 (t, J=7.9 Hz, 1H), 7.25 (m, 2H), 7.15 (s, 1H), 5.59 (d, J=8.4 Hz, 1H), 5.55 (m, 0.5H), 5.44 (m, 0.5H), 4.66 (d, J=17.1 Hz, 1H), 4.61 (m, 2H), 4.43 (m, 2H), 4.32 (m, 1H), 4.03 (d, J=17.5 Hz, 1H), 3.96 (s, 3H), 0.75 (d, J=6.5 Hz, 3H).

Workup

  1. customThe reaction was placed in an oil bath
  2. washThe ethyl acetate layer was washed with brine (50 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated on rotary evaporator
  6. customThe crude isolate
  7. customwas purified by silica gel chromatography
  8. washeluting with a 0-50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-9b676ef669384553b4cf7c79c44c0e45
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

Loading…