Hydrochloric Acid → HCID 89462837, compound

HRID 1473273Notes

Reaction equation

HRID 1473273 reaction equation
[F:1][C:2]1[CH:40]=[CH:39][C:5]([CH2:6][N:7]2[C:11]3[C:12](=[O:34])[N:13]([CH3:33])[C:14]([CH:23]([O:26]C4CCCCO4)[C:24]#N)=[C:15]([C:16]4[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=4)[C:10]=3[C:9]3[CH2:35][O:36][CH2:37][CH2:38][C:8]2=3)=[CH:4][CH:3]=1.[OH-:41].[Na+].Cl.[Si](C=[N+]=[N-])(C)(C)C.[CH3:51][OH:52]>CCOCC.C(O)C>[F:1][C:2]1[CH:40]=[CH:39][C:5]([CH2:6][N:7]2[C:11]3[C:12](=[O:34])[N:13]([CH3:33])[C:14]([CH:23]([OH:26])[C:24]([O:52][CH3:51])=[O:41])=[C:15]([C:16]4[CH:17]=[CH:18][C:19]([CH3:22])=[CH:20][CH:21]=4)[C:10]=3[C:9]3[CH2:35][O:36][CH2:37][CH2:38][C:8]2=3)=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 167693TrimethylsilyldiazomethaneHCID 89473318HCID 89473318, compound

Product 1

HCID 89462837HCID 89462837, compoundYield 16.89%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
140 °C

Procedure

A 6 mL microwave vial was charged with 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), Ethanol (5 ml) and 20% NaOH (2.54 ml, 14.60 mmol). The reaction vessel was sealed and heated in a 140° C. oil bath. After 18 h, the reaction mixture was cooled in an ice bath and conc HCl was added until pH <2. The residue was suspended in a mixture of MeOH (2 mL) and Et2O (2 mL), cooled to 0° C. and treated dropwise with TMS diazomethane (0.628 ml, 1.256 mmol). The reaction mixture was concentrated in vacuo and purified by ISCO (0-50% EtOAc-hexanes) to afford methyl 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-hydroxyacetate (26 mg, 0.053 mmol, 16.89% yield) as a white solid. LCMS (m/z) ES+=491 (M+1).

Workup

  1. customThe reaction vessel was sealed
  2. temperaturethe reaction mixture was cooled in an ice bath
  3. temperaturecooled to 0° C.
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. custompurified by ISCO (0-50% EtOAc-hexanes)

Sources & evidence

ORD record
ord-67e3f234002e4fc5a88f8e0f65da3ad9
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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