Hydrochloric Acid → HCID 89463057, compound

HRID 1473227Notes

Reaction equation

HRID 1473227 reaction equation
[CH2:1]([N:8]1[C:12]2[C:13](=[O:39])[N:14]([CH3:38])[C:15]([CH:28]([O:31]C3CCCCO3)[C:29]#N)=[C:16]([C:17]3[C:18]([CH3:27])=[C:19]4[C:24](=[CH:25][CH:26]=3)[O:23][CH2:22][CH2:21][CH2:20]4)[C:11]=2[CH:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-:40].[Na+].Cl.[Si](C=[N+]=[N-])(C)(C)C.Cl(O)(=O)(=O)=[O:51].[C:55]([O:58][CH2:59]C)(=[O:57])[CH3:56]>C(O)C>[CH2:1]([N:8]1[C:12]2[C:13](=[O:39])[N:14]([CH3:38])[C:15]([CH:56]([O:40][C:2]([CH3:7])([CH3:3])[CH3:1])[C:55]([O:58][CH3:59])=[O:57])=[C:16]([C:17]3[C:18]([CH3:27])=[C:19]4[C:24](=[CH:25][CH:26]=3)[O:23][CH2:22][CH2:21][CH2:20]4)[C:11]=2[CH:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:1]([N:8]1[C:12]2[C:13](=[O:39])[N:14]([CH3:38])[C:15]([CH:28]([OH:31])[C:29]([O:57][CH3:55])=[O:51])=[C:16]([C:17]3[C:18]([CH3:27])=[C:19]4[C:24](=[CH:25][CH:26]=3)[O:23][CH2:22][CH2:21][CH2:20]4)[C:11]=2[CH:10]=[CH:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 24247Perchloric AcidHCID 167693TrimethylsilyldiazomethaneHCID 89462939HCID 89462939, compound

Product 2

HCID 89463057HCID 89463057, compoundHCID 89473307HCID 89473307, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
140 °C

Procedure

A solution of 2-(1-benzyl-6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-((tetrahydro-2H-pyran-2-yl)oxy)acetonitrile (1.8 g, 3.09 mmol) in Ethanol (50 mL) was treated with NaOH (25 mL, 144 mmol) and the mixture was heated at 140° C. in a sealed tube overnight. HCl (conc.) was added until pH<2 and then the mixture was extracted with ethyl acetate. The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. The resulting residue was dissolved in Methanol (30 mL), cooled to 0° C. and then treated with TMS-diazomethane (6.19 mL, 12.38 mmol). The mixture was stirred for 2 hours and then concentrated. The resulting residue was dissolved in t-Butyl acetate (10 mL), treated with perchloric acid (0.186 mL, 3.09 mmol) and then stirred at ambient temperature overnight. The mixture was diluted with ethyl acetate, washed with 1M NaOH, then brine. The organic phase was then dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel (0-70% ethyl acetate/hexanes) to afford the title compound (280 mg) as well as methyl 2-(1-benzyl-6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-hydroxyacetate (500 mg). An ice cold solution of methyl 2-(1-benzyl-6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-hydroxyacetate (500 mg) in t-Butyl acetate (5 mL) was treated with perchloric acid (1 eq.) then kept at 0° C. for 2 days without stirring. The mixture was diluted with ethyl acetate, washed with 1M NaOH, then brine. The organic phase was then dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel (0-70% ethyl acetate/hexanes) to afford the title compound (290 mg). The material from each purification was combined to give the title compound (570 mg, 34% yield). 1H NMR (400 MHz, CHLOROFORM-d) ppm 7.37-7.29 (m, 5H), 7.15 (m, 1H), 7.02-6.91 (m, 1H), 6.74 (m, 1H), 5.99-5.67 (m, 3H), 5.28 (s, 0.7H), 5.10 (s, 0.3H), 4.27-4.15 (m, 2H), 3.77 (s, 2H), 3.73 (s, 1H), 3.67 (s, 3H), 2.77-2.58 (m, 2H), 2.17-2.03 (m, 2H), 1.92 (s, 3H), 1.12 (s, 3H), 0.97 (s, 6H); LC/MS (m/z) ES+=529 (M+1).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe combined organics were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe resulting residue was dissolved in Methanol (30 mL)
  7. temperaturecooled to 0° C.
  8. concentrationconcentrated
  9. dissolutionThe resulting residue was dissolved in t-Butyl acetate (10 mL)
  10. stirringstirred at ambient temperature overnight
  11. washwashed with 1M NaOH
  12. dry with materialThe organic phase was then dried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe residue was purified on silica gel (0-70% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-b8cbf0256f444bb8a79e439ee388e63a
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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