Lithium Hydroxide → HCID 72189373, compound

HRID 531289Notes

Reaction equation

HRID 531289 reaction equation
[F:1][C:2]([F:52])([F:51])[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:43]=[CH:42][C:37]([C:38]([O:40]C)=[O:39])=[CH:36][C:35]=5[CH3:44])[CH:29]=[N:30][C:31]=4[O:32][CH3:33])=[CH:24][N:23]=[C:22]([N:45]4[CH2:48][CH:47]([F:49])[CH2:46]4)[N:21]=3)[C@H:14]2[CH3:50])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[Li+]>O1CCOCC1>[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:43]=[CH:42][C:37]([C:38]([OH:40])=[O:39])=[CH:36][C:35]=5[CH3:44])[CH:29]=[N:30][C:31]=4[O:32][CH3:33])=[CH:24][N:23]=[C:22]([N:45]4[CH2:48][CH:47]([F:49])[CH2:46]4)[N:21]=3)[C@H:14]2[CH3:50])[CH:4]=[C:3]([C:2]([F:52])([F:51])[F:1])[CH:8]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 90009155HCID 90009155, compound

Product 1

HCID 72189373HCID 72189373, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Methyl 4-{5-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(3-fluoroazetidin-1-yl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3-methylbenzoate (Step A, 200 mg, 0.273 mmol) was dissolved in 1,4-dioxane (5 mL). Added 0.5N lithium hydroxide (2.5 mL, 1.25 mmol) and stirred at room temperature for 3 hours at which time LCMS showed complete hydrolysis. The reaction was quenched by adding 1.25 mL of 1N HCl, followed by water. The reaction was extracted with ethyl acetate. The ethyl acetate layer was dried over sodium sulfate, filtered and evaporated. The crude isolate was purified on a BIOTAGE SNAP 30 g C18 column, eluting with 40-100% CH3CN/water (0.05% TFA). The purified fractions were partitioned between pH 7 phosphate buffer and ethyl acetate. The aqueous was extracted a second time with ethyl acetate, then washed with pH 7.0 buffer and brine. The organic was dried over sodium sulfate, filtered and evaporated to give the title compound. LCMS (M+H)+: 720.4. 1H NMR (CDCl3, 500 MHz): δ 8.22 (d, 1H), 8.20 (s, 1H), 8.04 (s, 1H), 7.98 (d, 1H), 7.89 (s, 1H), 7.74 (s, 2H), 7.49 (d, 1H), 7.35 (d, 1H) 5.68 (d, 1H), 5.51 (m, 0.5H), 5.40 (m, 0.5H), 4.74 (d, 1H), 4.47 (m, 3H), 4.32 (m, 2H), 4.00 (d, s, 4H), 2.39 (s, 3H), 0.75 (d, 3H). RTA IC50: 12 nM.

Workup

  1. customhydrolysis
  2. customThe reaction was quenched
  3. additionby adding 1.25 mL of 1N HCl
  4. extractionThe reaction was extracted with ethyl acetate
  5. dry with materialThe ethyl acetate layer was dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude isolate
  9. customwas purified on a BIOTAGE SNAP 30 g C18 column
  10. washeluting with 40-100% CH3CN/water (0.05% TFA)
  11. customThe purified fractions were partitioned between pH 7 phosphate buffer and ethyl acetate
  12. extractionThe aqueous was extracted a second time with ethyl acetate
  13. washwashed with pH 7.0 buffer
  14. dry with materialThe organic was dried over sodium sulfate
  15. filtrationfiltered
  16. customevaporated

Sources & evidence

ORD record
ord-3c213a88fc29460a903b2394f6509f66
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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