Triethylamine → ethyl 2-(1-(5-chloro-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-1-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-4-carboxylate

HRID 715288Notes

Reaction equation

HRID 715288 reaction equation
Cl[C:2]1[C:7]2[CH2:8][N:9]([CH:12]([C:14]3[CH:15]=[N:16][C:17]([O:21][CH2:22][C:23]([F:26])([F:25])[F:24])=[C:18]([Cl:20])[CH:19]=3)[CH3:13])[C:10](=[O:11])[C:6]=2[CH:5]=[CH:4][N:3]=1.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.CN([CH:66]=[O:67])C.[CH3:68][CH2:69][OH:70]>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:20][C:18]1[CH:19]=[C:14]([CH:12]([N:9]2[C:10](=[O:11])[C:6]3[CH:5]=[CH:4][N:3]=[C:2]([C:66]([O:70][CH2:69][CH3:68])=[O:67])[C:7]=3[CH2:8]2)[CH3:13])[CH:15]=[N:16][C:17]=1[O:21][CH2:22][C:23]([F:26])([F:25])[F:24]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 19794673N,N-dimethylformamide ethanolHCID 898746024-chloro-2-(1-(5-chloro-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one

Product 1

HCID 89874895ethyl 2-(1-(5-chloro-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-1-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-4-carboxylateYield 73%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-chloro-2-(1-(5-chloro-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one (200 mg, 0.49 mmol, Intermediate-9, single enantiomer), palladium(II) acetate (33 mg, 0.15 mmol, 1,3-bis(diphenylphosphino)propane (20 mg, 0.049 mmol), and triethylamine (150 mg, 1.5 mmol) in DMF/EtOH (2:1, 14 mL) is heated at 100° C. overnight under carbon monoxide atmosphere. The mixture is diluted with water, and filtered through a pad of Celite™. The Celite™ pad is washed with EtOAc/toluene (2:1) mixed solvent. The filtrate is washed with water, brine, and dried over sodium sulfate. The organic layer is filtered, and the filtrate is concentrated. The residue is purified by column chromatography on silica gel eluting with n-hexane/EtOAc (1:1 to 1:2) to give 160 mg (73% yield) of the title compound as yellow solid.

Workup

  1. filtrationfiltered through a pad of Celite™
  2. washThe Celite™ pad is washed with EtOAc/toluene (2:1)
  3. additionmixed solvent
  4. washThe filtrate is washed with water, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationThe organic layer is filtered
  7. concentrationthe filtrate is concentrated
  8. customThe residue is purified by column chromatography on silica gel eluting with n-hexane/EtOAc (1:1 to 1:2)

Sources & evidence

ORD record
ord-83ca7ee3a02b45c4996a372ae88089df
Source dataset
uspto-grants-2015_11
Patent number
US09187475B2

Reaction notes

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