Pyridine → Ly-2886721

HRID 2060759Notes

Reaction equation

HRID 2060759 reaction equation
C([NH:9][C:10]1[S:11][CH2:12][C@@H:13]2[CH2:18][O:17][CH2:16][C@:14]2([C:19]2[CH:20]=[C:21]([NH:26][C:27](=[O:35])[C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][N:29]=3)[CH:22]=[CH:23][C:24]=2[F:25])[N:15]=1)(=O)C1C=CC=CC=1.CO[NH3+].[Cl-].N1C=CC=CC=1>C(O)C>[NH2:9][C:10]1[S:11][CH2:12][C@@H:13]2[CH2:18][O:17][CH2:16][C@:14]2([C:19]2[CH:20]=[C:21]([NH:26][C:27](=[O:35])[C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][N:29]=3)[CH:22]=[CH:23][C:24]=2[F:25])[N:15]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 11639O-methylhydroxylammonium chlorideHCID 57504891N-(3-((4aS,7aS)-2-Benzamido-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-7a-yl)-4-fluorophenyl)-5-fluoropicolinamide

Product 1

HCID 49837968Ly-2886721Yield 108.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of N-(3-((4aS,7aS)-2-benzamido-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-7a-yl)-4-fluorophenyl)-5-fluoropicolinamide (23.7 g 40.8 mmol), o-methylhydroxylamine hydrochloride (34.4 g, 412 mmol) and pyridine (33.3 mL) in ethanol (735 mL) is heated to 50° C. for 4 h. The mixture is concentrated. The residue is washed twice with methyl tert-butyl ether (2×250 mL) and poured into a saturated aqueous solution of sodium bicarbonate (453 mL). The suspension is shaken for 5 min and extracted with dichloromethane (1×1 L and 2×0.5 L). The organic layer is washed with water (0.5 L) dried over magnesium sulfate and the solvent is removed under reduced pressure to afford a solid. Additional solid is obtained from the aqueous phase by filtration. The solids are combined and triturated with water (300 mL) in an ultrasound bath for 30 min. The suspension is filtered off, washed with water, and dried under vacuum to give title compound (17.3 g, 100%). ES/MS m/e: 391 (M+1).

Workup

  1. concentrationThe mixture is concentrated
  2. washThe residue is washed twice with methyl tert-butyl ether (2×250 mL)
  3. additionpoured into a saturated aqueous solution of sodium bicarbonate (453 mL)
  4. extractionextracted with dichloromethane (1×1 L and 2×0.5 L)
  5. washThe organic layer is washed with water (0.5 L)
  6. dry with materialdried over magnesium sulfate
  7. customthe solvent is removed under reduced pressure
  8. customto afford a solid
  9. customAdditional solid is obtained from the aqueous phase by filtration
  10. customtriturated with water (300 mL) in an ultrasound bath for 30 min
  11. filtrationThe suspension is filtered off
  12. washwashed with water
  13. customdried under vacuum

Sources & evidence

ORD record
ord-7fbb604f92e0465c9287f4fe3bfcbf4f
Source dataset
uspto-grants-2012_10
Patent number
US08278441B2

Reaction notes

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