Hydrochloric Acid → HCID 58557824, compound

HRID 1969793Notes

Reaction equation

HRID 1969793 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)[CH:2]=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][CH2:2][OH:41])[N:5]=2)[CH2:27][C@@H:28]([NH:33][S:34]([CH:37]2[CH2:39][CH2:38]2)(=[O:36])=[O:35])[CH2:29]1)[CH3:32]

Participants

11

Reactant 5

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

Product 1

HCID 58557824HCID 58557824, compoundYield 20%

Reagents, catalysts & solvents 5

HCID 30318Osmium TetroxideCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 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 (0.170 g, 0.299 mmol, prepared using H with Preparation #12, Preparation #Z.1, HATU and DIEA, Q with Lawesson's reagent and mercury (II) trifluoroactate) in 1,4-dioxane (5 mL) and water (1.67 mL) was added sodium periodate (0.26 g, 1.198 mmol) followed by osmium tetroxide (4 wt % in water, 0.12 mL, 0.015 mmol). After about 4 h at ambient temperature, the reaction mixture was diluted with water (about 50 mL) and the resulting precipitate was collected by filtration. The crude aldehyde was dissolved in EtOH (10 mL) and NaBH4 (0.023 g, 0.60 mmol) was added to the reaction mixture. After about 2 h at ambient temperature, HCl (1 N aqueous, about 3 mL) was added to the reaction mixture. After stirring for about 30 min, the reaction mixture was concd in vacuo. The residue was partitioned between EtOAc (20 mL) and saturated aqueous NaHCO3 (20 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, 1.50 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 (40 g) eluting with 5% MeOH in DCM to provide N-((1S,3R,4S)-3-ethyl-4-(3-(2-hydroxyethyl)-6H-imidazo[1,5-a]pyrrolo[2,3-e]pyrazin-1-yl)cyclopentyl)cyclopropanesulfonamide (0.025 g, 20%) as a yellow solid: LC/MS (Table 1, Method a) Rt=1.67 min; MS m/z: 418 (M+H)+.

Workup

  1. filtrationthe resulting precipitate was collected by filtration
  2. dissolutionThe crude aldehyde was dissolved in EtOH (10 mL)
  3. waitAfter about 2 h at ambient temperature
  4. customThe residue was partitioned between EtOAc (20 mL) and saturated aqueous NaHCO3 (20 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. dissolutionThe crude alcohol was dissolved in 1,4-dioxane (10 mL)
  9. waitAfter about 4 h
  10. temperaturethe reaction mixture was cooled to ambient temperature
  11. customThe organic layer was separated
  12. customconcd in vacuo, and purified by chromatography on silica gel (40 g)
  13. washeluting with 5% MeOH in DCM

Sources & evidence

ORD record
ord-9ad762d9000b4124a0374f878aff4282
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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