Lithium Hydroxide → HCID 72189669, compound

HRID 531302Notes

Reaction equation

HRID 531302 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[O:13][C:12](=[O:14])[N:11]([CH2:15][C:16]3[C:21]([C:22]4[CH:23]=[C:24]([C:30]5[CH:39]=[CH:38][C:33]([C:34]([O:36]C)=[O:35])=[CH:32][C:31]=5[CH3:40])[CH:25]=[N:26][C:27]=4[O:28][CH3:29])=[CH:20][N:19]=[C:18]([N:41]4[CH2:44][CH:43]([F:45])[CH2:42]4)[N:17]=3)[C@H:10]2[CH3:46])[CH:5]=[C:6]([F:8])[CH:7]=1.[OH-].[Li+]>O1CCOCC1>[F:8][C:6]1[CH:5]=[C:4]([C@H:9]2[O:13][C:12](=[O:14])[N:11]([CH2:15][C:16]3[C:21]([C:22]4[CH:23]=[C:24]([C:30]5[CH:39]=[CH:38][C:33]([C:34]([OH:36])=[O:35])=[CH:32][C:31]=5[CH3:40])[CH:25]=[N:26][C:27]=4[O:28][CH3:29])=[CH:20][N:19]=[C:18]([N:41]4[CH2:42][CH:43]([F:45])[CH2:44]4)[N:17]=3)[C@H:10]2[CH3:46])[CH:3]=[C:2]([F:1])[CH:7]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 90009211HCID 90009211, compound

Product 1

HCID 72189669HCID 72189669, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Methyl 4-{5-[4-{[(4S,5R)-5-(3,5-difluorophenyl)-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, 65 mg, 0.103 mmol) was dissolved in 1,4-dioxane (2 mL). Added 0.5N lithium hydroxide (1.0 mL, 0.50 mmol) and stirred at room temperature for 2.5 hours at which time LCMS shows complete hydrolysis. The reaction was quenched by adding 0.50 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 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)+: 620.2. 1H NMR (CDCl3, 500 MHz): δ 8.21 (br, 1H), 8.20 (s, 1H), 8.02 (s, 1H), 7.97 (d, 1H), 7.47 (s, 1H), 7.33 (d, 1H), 6.81 (m, 3H), 5.50 (d, 1.5H), 5.40 (m, 0.5H), 4.69 (d, 1H), 4.47 (m, 2H), 4.33 (m, 3H), 4.00 (d, s, 4H), 2.38 (s, 3H), 0.76 (d, 3H). RTA IC50: 35 nM

Workup

  1. customhydrolysis
  2. customThe reaction was quenched
  3. additionby adding 0.50 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 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-952ff21e5be14e73a92210aa17ce51f2
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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