Acetic Acid → 8-(1-((R)-1,1-dimethylethyl sulfinamido)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide

HRID 572796Notes

Reaction equation

HRID 572796 reaction equation
[C:1]([S:5]([N:7]=[C:8]([C:10]1[CH:11]=[C:12]([C:27]([N:29]([CH3:31])[CH3:30])=[O:28])[CH:13]=[C:14]2[C:19]=1[O:18][C:17]([N:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1)=[CH:16][C:15]2=[O:26])[CH3:9])=[O:6])([CH3:4])([CH3:3])[CH3:2].C(O)(=O)C.[B-]C#N.[Na+].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.CO>[CH3:4][C:1]([CH3:2])([S@:5]([NH:7][CH:8]([C:10]1[CH:11]=[C:12]([C:27]([N:29]([CH3:31])[CH3:30])=[O:28])[CH:13]=[C:14]2[C:19]=1[O:18][C:17]([N:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1)=[CH:16][C:15]2=[O:26])[CH3:9])=[O:6])[CH3:3]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 10340Sodium CarbonateHCID 20587905Sodium cyanoborohydride [MI]HCID 767105838-(1-(tert-butylsulfinylimino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide

Product 1

HCID 582350578-(1-((R)-1,1-dimethylethyl sulfinamido)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamideYield 5.53%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-15 °C

Procedure

The 8-(1-(tert-butylsulfinylimino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide was diluted in DCM (35 mL) and MeOH (35 mL), acetic acid (4.6 mL, 80.4 mmol) and sodium cyanotrihydroborate (1.9 g, 30.2 mmol) was added at −15° C. The resulting mixture was stirred at −15° C. for 5 hrs then allowed to warm to 0° C. A sat. sol. of Na2CO3 was added at 0° C. until pH˜8-9 and extracted with DCM (×2). The organic phase was washed with brine, dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel (column SiO2, 15-40 μm-150 g Merck) eluting with 5 to 15% EtOH in DCM. The fractions containing impure product were concentrated down and repurified using the same system. The fractions containing pure 8-(1-((R)-1,1-dimethylethylsulfinamido)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide were combined and the solvent was evaporated to dryness to afford 2.48 g, (5.52 mmol, 54.9%) as a white foam. The fractions containing a mixture of diastereoisomers were combined, concentrated and purified by preparative HPLC on a Waters X-Bridge system. The fractions containing the desired compound were evaporated to dryness to afford a further crop of 8-(1-((R)-1,1-dimethylethylsulfinamido)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (0.25 g, 0.556 mmol, 5.53%) as a white foam. These 2 batches (2.48 g) and (0.25 g) were combined to give 8-(1-((R)-1,1-dimethylethylsulfinamido)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (2.73 g, 60%, diastereomeric excess >95%). Mass Spectrum: M+H+ 450.

Workup

  1. temperatureto warm to 0° C
  2. extractionextracted with DCM (×2)
  3. washThe organic phase was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe crude product was purified by flash chromatography on silica gel (column SiO2, 15-40 μm-150 g Merck)
  7. washeluting with 5 to 15% EtOH in DCM
  8. additionThe fractions containing impure product
  9. concentrationwere concentrated down
  10. customrepurified
  11. additionThe fractions containing pure 8-(1-((R)-1,1-dimethylethylsulfinamido)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide
  12. customthe solvent was evaporated to dryness
  13. customto afford 2.48 g, (5.52 mmol, 54.9%) as a white foam
  14. additionThe fractions containing
  15. additiona mixture of diastereoisomers
  16. concentrationconcentrated
  17. custompurified by preparative HPLC on a Waters X-Bridge system
  18. additionThe fractions containing the desired compound
  19. customwere evaporated to dryness

Sources & evidence

ORD record
ord-17004a14fcb54becba4eda73681bf04f
Source dataset
uspto-grants-2015_05
Patent number
US09029374B2

Reaction notes

Loading…