2,4-Dimethoxybenzylamine → 4-[(2,4-dimethoxybenzyl)amino]-2-methyl-1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one

HRID 511556Notes

Reaction equation

HRID 511556 reaction equation
Cl[C:2]1[C:7]2[C:8](=[O:12])[N:9]([CH3:11])[CH2:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[CH3:13][O:14][C:15]1[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=[CH:19][C:16]=1[CH2:17][NH2:18]>CN1CCCC1=O>[CH3:13][O:14][C:15]1[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=[CH:19][C:16]=1[CH2:17][NH:18][C:2]1[C:7]2[C:8](=[O:12])[N:9]([CH3:11])[CH2:10][C:6]=2[CH:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 5972502,4-DimethoxybenzylamineHCID 121631514-Chloro-1,2-dihydro-2-methyl-3H-pyrrolo[3,4-c]pyridin-3-one2×

Product 1

HCID 672542684-[(2,4-dimethoxybenzyl)amino]-2-methyl-1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 4-chloro-2-methyl-1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one (Compound 310E, 1.5 g, 8.2 mmol) in N-Methylpyrrolidinone (20 mL) was charged with 2,4-dimethoxy benzylamine (2.5 mL, 16 mmol) and irradiated in the microwave for 40 min at 160° C. The reaction mixture was quenched with water (15 mL) and extracted with EtOAc (20 mL). The aqueous layer was back-extracted with EtOAc (3×10 mL). The combined organic fractions were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to yield a red solid. The crude material was purified by silica gel chromatography on the combi-flash Rf system using Heptane/EtOAc (70:30→0:100) as eluent. The fractions containing product were combined and concentrated under reduced pressure to yield an orange solid. 1H NMR (DMSO-d6, 400 MHz): δ=8.10 (d, J=5.30 Hz, 1H), 7.11 (d, J=8.34 Hz, 1H), 7.01-7.07 (m, 1H), 6.72 (d, J=5.31 Hz, 1H), 6.57 (d, J=2.27 Hz, 1H), 6.44 (dd, J=2.53, 8.34 Hz, 1H), 4.53 (d, J=6.06 Hz, 2H), 4.37 (s, 2H), 3.81 (s, 3H), 3.73 (s, 3H), 2.98 (s, 3H). MS (ES+): m/z 314.14 [MH+] (TOF, polar).

Workup

  1. customirradiated in the microwave for 40 min at 160° C
  2. customThe reaction mixture was quenched with water (15 mL)
  3. extractionextracted with EtOAc (20 mL)
  4. extractionThe aqueous layer was back-extracted with EtOAc (3×10 mL)
  5. washThe combined organic fractions were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto yield a red solid
  10. customThe crude material was purified by silica gel chromatography on the combi-flash Rf system
  11. additionThe fractions containing product
  12. concentrationconcentrated under reduced pressure
  13. customto yield an orange solid

Sources & evidence

ORD record
ord-808c75669ca64ac58926ae44a15e17bf
Source dataset
uspto-grants-2015_08
Patent number
US09096624B2

Reaction notes

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