Acetic Acid → HCID 66673244, compound

HRID 423431Notes

Reaction equation

HRID 423431 reaction equation
C(O[C:6](=O)[NH:7][C@@H:8]1[CH2:12][CH2:11][N:10]([C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH2:24][CH2:23][C:22]4[CH:25]=[C:26]([C:28]5[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=5)[S:27][C:21]=4[C:20]3=[O:35])=[CH:15][N:14]=2)[CH2:9]1)(C)(C)C.[C:37](O)([C:39](F)(F)F)=O.CC(O)=O.C(O[C:51]1(O[Si](C)(C)C)[CH2:53][CH2:52]1)C.[BH3-]C#N.[Na+]>C(Cl)(Cl)Cl.CCOC(C)=O.[OH-].[Na+]>[Cl:34][C:31]1[CH:32]=[CH:33][C:28]([C:26]2[S:27][C:21]3[C:20](=[O:35])[N:19]([C:16]4[CH:15]=[N:14][C:13]([N:10]5[CH2:11][CH2:12][C@@H:8]([N:7]([CH:51]6[CH2:53][CH2:52]6)[CH:6]6[CH2:39][CH2:37]6)[CH2:9]5)=[CH:18][CH:17]=4)[CH2:24][CH2:23][C:22]=3[CH:25]=2)=[CH:29][CH:30]=1

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 6422Trifluoroacetic acidHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 66674063HCID 66674063, compound

Product 1

HCID 66673244HCID 66673244, compoundYield 93%

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Procedure

Dissolve ((R)-1-{5-[2-(4-chloro-phenyl)-7-oxo-4,7-dihydro-5H-thieno [2,3-c]pyridin-6-yl]-pyridin-2-yl}-pyrrolidin-3-yl)-carbamic acid tert-butyl ester (0.393 g, 0.750 mmol) in CHCl3 (5 mL) and treat with TFA (2 mL). Stir the mixture at RT for 30 min. Remove the excess reagent in vacuo. Dissolve the crude material in CH3OH (10 mL) and treat with HOAc (90.22 mL, 3.93 mmol), and (1-ethoxy-cyclopropoxy)trimethylsilane (0.47 mL, 2.36 mmol). Stir the mixture at RT for 10 min. Add NaBH3CN (90.36 g, 5.69 mmol) and reflux the reaction overnight. Dilute the mixture with EtOAc (50 mL) and 2.0 M NaOH (920 mL) and then stir at RT for 5 min. Filter and wash the mixture with EtOAc (30 mL). Separate the organic layer and dry with Na2SO4, filter, and concentrate. Purify the crude material by chromatography, eluting with 5% CH3OH (2M NH3)/CHCl3 to give 0.35 g (93%) of 2-(4-chloro-phenyl)-6-[6-((R)-3-dicyclopropylamino-pyrrolidin-1-yl)-pyridin-3-yl]-5,6-dihydro-4H-thieno[2,3-c]pyridin-7-one.

Workup

  1. customRemove the excess reagent in vacuo
  2. dissolutionDissolve the crude material in CH3OH (10 mL)
  3. stirringStir the mixture at RT for 10 min
  4. customthe reaction overnight
  5. stirringstir at RT for 5 min
  6. filtrationFilter
  7. washwash the mixture with EtOAc (30 mL)
  8. customSeparate the organic layer
  9. dry with materialdry with Na2SO4
  10. filtrationfilter
  11. concentrationconcentrate
  12. customPurify the crude material by chromatography
  13. washeluting with 5% CH3OH (2M NH3)/CHCl3

Sources & evidence

ORD record
ord-7e4dae82d5924fb8893b188262156117
Source dataset
uspto-grants-2012_01
Patent number
US08101764B2

Reaction notes

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