Lithium Hydroxide → HCID 72189372, compound

HRID 531294Notes

Reaction equation

HRID 531294 reaction equation
[F:1][C:2]([F:53])([F:52])[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[CH2:50][CH2:49][O:48][CH2:47][CH2:46]4)[N:21]=3)[C@H:14]2[CH3:51])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[Li+]>O1CCOCC1>[F:53][C:2]([F:1])([F:52])[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]([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[CH2:50][CH2:49][O:48][CH2:47][CH2:46]4)[N:21]=3)[C@H:14]2[CH3:51])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 90009166HCID 90009166, compound

Product 1

HCID 72189372HCID 72189372, 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-(morpholin-4-yl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3-methylbenzoate (Step A, 200 mg, 0.268 mmol) was dissolved in 1,4-dioxane (5.0 mL). Lithium hydroxide (0.5M, 2.4 mL, 1.20 mmol) was added, and the reaction was stirred at room temperature for 2 hours. The reaction was quenched by adding 1.20 mL of 1N HCl, followed by water. The aqueous reaction mixture was extracted with ethyl acetate, then dried over sodium sulfate, filtered and evaporated. Purified on BIOTAGE SNAP C18 column, eluting with 40-100% CH3CN/water (0.05% TFA) and recovering purified fractions by partitioning them between pH 7 phosphate buffer and ethyl acetate. Extracted the aqueous a second time with ethyl acetate, then washed the combined organics with pH 7.0 buffer and brine. The organic was dried over sodium sulfate, filtered and evaporated to give the titled compound. LCMS (M+H)+: 732.5. 1H NMR (CDCl3, 500 MHz): δ 8.22 (d, 1H), 8.20 (s, 1H), 8.03 (s, 1H), 7.99 (d, 1H), 7.88 (s, 1H), 7.72 (s, 2H), 7.48 (d, 1H), 7.35 (d, 1H), 5.64 (d, 1H), 4.76 (d, 1H), 4.32 (m, 1H), 4.00 (m, s, 4H), 3.86 (m, 4H), 3.81 (m, 4H), 2.39 (s, 3H), 0.72 (d, 3H). RTA IC50: 13 nM.

Workup

  1. customThe reaction was quenched
  2. additionby adding 1.20 mL of 1N HCl
  3. extractionThe aqueous reaction mixture was extracted with ethyl acetate
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customPurified on BIOTAGE SNAP C18 column
  8. washeluting with 40-100% CH3CN/water (0.05% TFA)
  9. customrecovering
  10. custompurified fractions
  11. customby partitioning them between pH 7 phosphate buffer and ethyl acetate
  12. extractionExtracted the aqueous a second time with ethyl acetate
  13. washwashed the combined organics with pH 7.0 buffer
  14. dry with materialThe organic was dried over sodium sulfate
  15. filtrationfiltered
  16. customevaporated

Sources & evidence

ORD record
ord-42d32ed664ec4453835f6d6556ba2c66
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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