Hydrochloric Acid → HCID 58557444, compound

HRID 1969792Notes

Reaction equation

HRID 1969792 reaction equation
[CH2:1]([C:4]1[N:5]=[C:6]([C@@H:26]2[C@H:30]([CH2:31][CH3:32])[CH2:29][C@H:28]([NH:33][S:34]([CH:37]3[CH2:39][CH2:38]3)(=[O:36])=[O:35])[CH2:27]2)[N:7]2[C:12]3[CH:13]=[CH:14][N:15](S(C4C=CC(C)=CC=4)(=O)=O)[C:11]=3[N:10]=[CH:9][C:8]=12)C=C.I([O-])(=O)(=O)=[O:41].[Na+].[BH4-].[Na+].Cl.[OH-].[Na+]>O1CCOCC1.O.CCOC(C)=O.[NH4+].[Cl-].[Os](=O)(=O)(=O)=O>[CH2:31]([C@H:30]1[C@@H:26]([C:6]2[N:7]3[C:12]4[CH:13]=[CH:14][NH:15][C:11]=4[N:10]=[CH:9][C:8]3=[C:4]([CH2:1][OH:41])[N:5]=2)[CH2:27][C@@H:28]([NH:33][S:34]([CH:37]2[CH2:39][CH2:38]2)(=[O:35])=[O:36])[CH2:29]1)[CH3:32]

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 23667635Sodium periodateHCID 67999341HCID 67999341, compound

Product 1

HCID 58557444HCID 58557444, compoundYield 6%

Reagents, catalysts & solvents 5

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent2×HCID 25517Ammonium ChlorideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of N-((1S,3S,4R)-3-(3-allyl-6-tosyl-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)-4-ethylcyclopentyl)cyclopropanesulfonamide (0.17 g, 0.299 mmol, prepared using H with Preparation #12, Preparation #Z.1, HATU and DIEA, and Q with Lawesson's reagent and mercury (II) trifluoroacetate) in 1,4-dioxane (5 mL) and water (1.7 mL) was added sodium periodate (0.26 g, 1.2 mmol) followed by osmium tetroxide (4 wt % in water, 0.117 mL, 0.015 mmol). After about 48 h at ambient temperature, the reaction mixture was diluted with water (about 50 mL) and EtOAc (30 mL). The organic layer was separated, dried over anhydrous Na2SO4, filtered, and concd in vacuo. The crude aldehyde was dissolved in EtOH (10 mL) and NaBH4 (0.023 g, 0.599 mmol) was added to the reaction mixture. After about 2 h at ambient temperature, HCl (1 N aqueous, about 3 mL) was added. After stirring for about 30 min, the reaction mixture was concd in vacuo. The residue was partitioned between EtOAc (30 mL) and saturated aqueous NaHCO3 (30 mL). The organic layer was separated, dried over anhydrous Na2SO4, filtered, and concd in vacuo. The crude alcohol was dissolved in 1,4-dioxane (10 mL) and NaOH (2 N aqueous, 1.5 mL, 2.99 mmol) was added. The reaction mixture was heated to about 80° C. After about 4 h, the reaction mixture was cooled to ambient temperature and diluted with EtOAc (30 mL) and saturated aqueous NH4Cl (30 mL). The organic layer was separated, concd in vacuo, and purified by chromatography on silica gel eluting with 10-50% MeCN in DCM to provide N-((1S,3R,4S)-3-ethyl-4-(3-(hydroxymethyl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)cyclopentyl)cyclopropanesulfonamide (0.007 g, 6%) as a yellow solid: LC/MS (Table 1, Method a) Rt=1.59 min; MS m/z: 404 (M+H)+.

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over anhydrous Na2SO4
  3. filtrationfiltered
  4. dissolutionThe crude aldehyde was dissolved in EtOH (10 mL)
  5. waitAfter about 2 h at ambient temperature
  6. customThe residue was partitioned between EtOAc (30 mL) and saturated aqueous NaHCO3 (30 mL)
  7. customThe organic layer was separated
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. dissolutionThe crude alcohol was dissolved in 1,4-dioxane (10 mL)
  11. waitAfter about 4 h
  12. temperaturethe reaction mixture was cooled to ambient temperature
  13. customThe organic layer was separated
  14. customconcd in vacuo, and purified by chromatography on silica gel eluting with 10-50% MeCN in DCM

Sources & evidence

ORD record
ord-eeccc97b5b2240f1aaaef0b003401853
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

Loading…