Hydrochloric Acid → N-(tert-butyl)-5-[({2-[(2,3-difluorobenzyl)thio]-6-[(1R)-2-hydroxy-1-methylethoxy]pyrimidin-4-yl]amino)sulfonyl]-2-furamide

HRID 1958975Notes

Reaction equation

HRID 1958975 reaction equation
[C:1]([NH:5][C:6]([C:8]1[O:12][C:11]([S:13]([NH:16][C:17]2[N:22]=[C:21]([S:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:26]=3[F:32])[N:20]=[C:19]([O:33][C@H:34]([CH3:40])[C:35](OCC)=[O:36])[CH:18]=2)(=[O:15])=[O:14])=[CH:10][CH:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Li+].Cl>C1COCC1>[C:1]([NH:5][C:6]([C:8]1[O:12][C:11]([S:13]([NH:16][C:17]2[CH:18]=[C:19]([O:33][C@H:34]([CH3:40])[CH2:35][OH:36])[N:20]=[C:21]([S:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:26]=3[F:32])[N:22]=2)(=[O:14])=[O:15])=[CH:10][CH:9]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 4148881Lithium borohydrideHCID 53628366ethyl (2R)-2-({6-[({5-[(tert-butylamino)carbonyl]-2-furyl}sulfonyl)amino]-2-[(2,3-difluorobenzyl)thio]pyrimidin-4-yl}oxy)propanoate

Product 1

HCID 59558781N-(tert-butyl)-5-[({2-[(2,3-difluorobenzyl)thio]-6-[(1R)-2-hydroxy-1-methylethoxy]pyrimidin-4-yl]amino)sulfonyl]-2-furamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl (2R)-2-({6-[({5-[(tert-butylamino)carbonyl]-2-furyl}sulfonyl)amino]-2-[(2,3-difluorobenzyl)thio]pyrimidin-4-yl}oxy)propanoate (the product of step iii) (0.25 g) in THF (10 mL) was added a solution of lithium borohydride (0.6 mL, 2.0M in hexanes) dropwise at 0° C. The mixture was warmed to room temperature and stirred for 18 h. After cooling to 0° C., 1N HCl (20 mL) was added slowly, and the mixture extracted with EtOAc (3×20 mL). The combined organic layers were dried (MgSO4), filtered and evaporated to dryness in vacuo. The resulting crude oil was purified by reverse phase HPLC (75% to 5% gradient of 0.2% aqueous trifluoroacetic acid in acetonitrile as eluent) to give the title compound as a white solid. Yield: 90 mg.

Workup

  1. temperatureAfter cooling to 0° C.
  2. extractionthe mixture extracted with EtOAc (3×20 mL)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated to dryness in vacuo
  6. customThe resulting crude oil was purified by reverse phase HPLC (75% to 5% gradient of 0.2% aqueous trifluoroacetic acid in acetonitrile as eluent)

Sources & evidence

ORD record
ord-e0be434c0f9e4d1aa1ad4f1581767d10
Source dataset
uspto-grants-2013_04
Patent number
US08410123B2

Reaction notes

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