Hydrochloric Acid → HCID 89473318, compound

HRID 1473272Notes

Reaction equation

HRID 1473272 reaction equation
[F:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][N:7]2[C:11]3[C:12](=[O:26])[N:13]([CH3:25])[C:14]([CH:23]=[O:24])=[C:15]([C:16]4[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=4)[C:10]=3[C:9]3[CH2:27][O:28][CH2:29][CH2:30][C:8]2=3)=[CH:4][CH:3]=1.[Si]([C:37]#[N:38])(C)(C)C.Cl.O1CCOCC1.[CH2:46]1[CH2:51][O:50][CH:49]=[CH:48][CH2:47]1.C([O-])(O)=O.[Na+]>ClCCl.[I-].[Zn+2].[I-].CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1.CCOC(C)=O.CCN(CC)CC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:11]3[C:12](=[O:26])[N:13]([CH3:25])[C:14]([CH:23]([O:24][CH:49]4[CH2:48][CH2:47][CH2:46][CH2:51][O:50]4)[C:37]#[N:38])=[C:15]([C:16]4[CH:17]=[CH:18][C:19]([CH3:22])=[CH:20][CH:21]=4)[C:10]=3[C:9]3[CH2:27][O:28][CH2:29][CH2:30][C:8]2=3)=[CH:31][CH:32]=1

Participants

12

Reactant 6

HCID 313Hydrochloric AcidHCID 80803,4-dihydro-2H-pyranHCID 312751,4-DioxaneHCID 82115Trimethylsilyl cyanideHCID 516892Sodium BicarbonateHCID 89462631HCID 89462631, compound

Product 1

HCID 89473318HCID 89473318, compoundYield 90.2%

Reagents, catalysts & solvents 5

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)CatalystHCID 9883512zinc(II)iodideCatalystHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

An ice cold solution of 5-(4-fluorobenzyl)-7-methyl-6-oxo-9-(p-tolyl)-1,3,4,5,6,7-hexahydropyrano[3′,4′:4,5]pyrrolo[2,3-c]pyridine-8-carbaldehyde (150 mg, 0.348 mmol) and Zinc iodide (86 mg, 0.697 mmol) in Dichloromethane (DCM) (1783 μl) was treated with TMS-CN (909 μl, 3.48 mmol) dropwise. After 30 min, the reaction mixture was quenched with a 10% solution of Na2S2O3. DCM was added and the layers were partitioned. The organic layer was washed with brine, dried (Na2SO4), filtered and concentrated. The residue was dissolved in MeOH (3 mL), cooled to 0° C. and treated dropwise with 1M HCl in 1,4-dioxane (697 μl, 0.697 mmol). After 1 h, the reaction mixture was concentrated in vacuo. The residue was then dissolved in DCM (3 mL) and treated with DHP (96 μl, 1.045 mmol) and PPTS (4.38 mg, 0.017 mmol). After 45 min, Et3N (0.5 mL) was added and the reaction mixture was poured into sat. aq. NaHCO3. EtOAc was added and the layers partitioned. The organic phase was washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by ISCO (0-50% EtOAc-hexanes) to afford 2-(5-(4-fluorobenzyl)-7-methyl-6-oxo-9-(p-tolyl)-1,3,4,5,6,7-hexahydropyrano[3′,4′:4,5]pyrrolo[2,3-c]pyridin-8-yl)-2-((tetrahydro-2H-pyran-2-yl)oxy)acetonitrile (170 mg, 0.314 mmol, 90% yield) as a white foam. LCMS (m/z) ES+=542 (M+1).

Workup

  1. customthe reaction mixture was quenched with a 10% solution of Na2S2O3
  2. additionDCM was added
  3. customthe layers were partitioned
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in MeOH (3 mL)
  9. waitAfter 1 h
  10. concentrationthe reaction mixture was concentrated in vacuo
  11. dissolutionThe residue was then dissolved in DCM (3 mL)
  12. waitAfter 45 min
  13. customthe layers partitioned
  14. washThe organic phase was washed with brine
  15. dry with materialdried (Na2SO4)
  16. filtrationfiltered
  17. concentrationconcentrated in vacuo
  18. customThe residue was purified by ISCO (0-50% EtOAc-hexanes)

Sources & evidence

ORD record
ord-f522e729c6c14dfd9c49991ea1eda9c3
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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