Hydrochloric Acid → methyl 2-(1-benzyl-4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate

HRID 1473187Notes

Reaction equation

HRID 1473187 reaction equation
[CH2:1]([N:8]1[C:12]2[C:13](=[O:28])[N:14]([CH3:27])[C:15]([CH2:24][C:25]#N)=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)[C:11]=2[CH:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-:29].[K+].Cl.[Si](C=[N+]=[N-])(C)(C)C.[CH2:39]([OH:41])C>O>[CH2:1]([N:8]1[C:12]2[C:13](=[O:28])[N:14]([CH3:27])[C:15]([CH2:24][C:25]([O:41][CH3:39])=[O:29])=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)[C:11]=2[CH:10]=[CH:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 702EthanolHCID 14797Potassium HydroxideHCID 167693TrimethylsilyldiazomethaneHCID 894630402-(1-benzyl-4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetonitrile

Product 1

HCID 89462962methyl 2-(1-benzyl-4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetateYield 78%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

A suspension of 2-(1-benzyl-4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetonitrile (3 g, 7.04 mmol) in Ethanol (60 mL) and Water (20 mL) was treated with KOH (3.95 g, 70.4 mmol) and then heated to 140° C. in a sealed tube for 24 hours. The mixture was cooled to 0° C. and then treated with 4N HCl until pH<2. The mixture was partly concentrated and then extracted with Ethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate, filtered and then concentrated. The residue was dissolved in Methanol (60.0 mL), cooled to 0° C. and then treated with TMS-diazomethane (35.2 mL, 70.4 mmol). The mixture was warmed to ambient temperature and then stirred for 20 minutes. Upon reaction completion, the mixture was cooled to 0° C., quenched with acetic acid and then concentrated. The residue was purified on silica gel (0-70% ethyl acetate/hexanes) to afford methyl 2-(1-benzyl-4-(4-chlorophenyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (2.3 g, 5.46 mmol, 78% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) ppm 7.40-7.44 (m, 2H) 7.25-7.35 (m, 7H) 7.00-7.04 (m, 1H) 5.88-5.94 (m, 1H) 5.80-5.88 (m, 2H) 3.74 (s, 3H) 3.63 (s, 2H) 3.59 (s, 3H); LCMS (m/z) ES+=421 (M+1).

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. concentrationThe mixture was partly concentrated
  3. extractionextracted with Ethyl acetate
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in Methanol (60.0 mL)
  9. temperaturecooled to 0° C.
  10. temperatureThe mixture was warmed to ambient temperature
  11. customUpon reaction completion
  12. temperaturethe mixture was cooled to 0° C.
  13. customquenched with acetic acid
  14. concentrationconcentrated
  15. customThe residue was purified on silica gel (0-70% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-62f1cb57ee1e4df18bdfd5747816a405
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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