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

HRID 715252Notes

Reaction equation

HRID 715252 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]([CH3:20])[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][OH:69]>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:20][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:68]([O:67][CH3:66])=[O:69])[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 21901440N,N-dimethylformamide methanolHCID 898749364-chloro-2-(1-(5-methyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one

Product 1

HCID 89874191methyl 2-(1-(5-methyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-1-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-4-carboxylateYield 52%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-chloro-2-(1-(5-methyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one (540 mg, 1.40 mmol, Intermediate-2, single enantiomer), palladium(II) acetate (190 mg, 0.84 mmol), 1,3-bis(diphenylphosphino)propane (115 mg, 0.28 mmol), and triethylamine (0.58 mL, 4.20 mmol) in DMF/MeOH (2.5:1, 14 mL) is heated at 100° C. under carbon monoxide atmosphere for 18 hours. The reaction mixture is cooled to rt and dilute with water. The mixture is filtered through a pad of Celite™ and the filtrate is extracted with n-hexane/EtOAc (1:1) mixed solvent. The combined extracts are washed with water, and brine. The organic extract is dried over sodium sulfate, filtrate, and volatiles are removed. The residue is purified by column chromatography on silica gel eluting with n-hexane/EtOAc (1:1 to 1:4) to give 300 mg (52% yield) of the title compound as brown amorphous solid.

Workup

  1. temperatureThe reaction mixture is cooled to rt
  2. filtrationThe mixture is filtered through a pad of Celite™
  3. extractionthe filtrate is extracted with n-hexane/EtOAc (1:1)
  4. additionmixed solvent
  5. washThe combined extracts are washed with water, and brine
  6. extractionThe organic extract
  7. dry with materialis dried over sodium sulfate, filtrate, and volatiles
  8. customare removed
  9. customThe residue is purified by column chromatography on silica gel eluting with n-hexane/EtOAc (1:1 to 1:4)

Sources & evidence

ORD record
ord-e97b5dcb21a94a9a9d1bb341edefe254
Source dataset
uspto-grants-2015_11
Patent number
US09187475B2

Reaction notes

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