Sodium Chloride → 3-methyl-1-(2-phenoxyphenyl)-6,7-dihydro-2H-pyrrolo[3,4-c]pyridin-4(5H)-one

HRID 2170230Notes

Reaction equation

HRID 2170230 reaction equation
O(C1C=CC=CC=1B(O)O)C1C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:23][C:24]1[NH:25][C:26](=[O:47])[C:27]2[C:28](=[C:30]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[O:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[NH:31][C:32]=2[CH3:33])N=1.[Cl-].[Na+]>C(O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C.COCCOC>[CH3:33][C:32]1[NH:31][C:30]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[O:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[C:28]2[CH2:23][CH2:24][NH:25][C:26](=[O:47])[C:27]=12

Participants

9

Reactant 4

HCID 5234Sodium ChlorideHCID 10340Sodium CarbonateHCID 2773559(2-Phenoxyphenyl)boronic acidHCID 1365969572,5-dimethyl-7-(2-phenoxyphenyl)-3,6-dihydro-4H-pyrrolo[3,4-d]pyrimidin-4-one

Product 1

HCID 862717523-methyl-1-(2-phenoxyphenyl)-6,7-dihydro-2H-pyrrolo[3,4-c]pyridin-4(5H)-oneYield 53%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 2 mL microwave reaction vessel equipped with stirbar was charged with Example 92f (0.010 g, 0.044 mmol), 2-phenoxyphenylboronic acid (0.023 g, 0.109 mmol), 2 M aqueous sodium carbonate (0.218 mL, 0.437 mmol) and bis(triphenylphosphine)palladium(II) dichloride (3.06 mg, 4.37 μmol) in ethanol (0.200 mL)/DME (0.200 mL) and sealed. The mixture was heated at 120° C. for 30 minutes in a Biotage Initiator 2 monomode microwave reactor, then cooled to ambient temperature. The mixture was shaken in a separatory funnel with 75 mL ethyl acetate and 50 mL saturated aqueous sodium chloride. The organics were dried over anhydrous sodium sulfate. After filtration and solvent removal the residue was purified by reverse phase HPLC (C18, 0-100% CH3CN/water (0.1% TFA)) to afford the title compound (7.3 mg, 53%). 1H NMR (300 MHz, CD3OD) δ 10.74 (bds, 1H), 7.42 (dd, J=1.9, 7.6 Hz, 1H), 7.31-7.18 (m, 4H), 7.02-6.96 (m, 2H), 6.85 (m, 2H), 3.36 (m, 2H), 2.73 (m, 2H), 2.44 (s, 3H). MS (ESI+) m/z 319.2 (M+H)+.

Workup

  1. customA 2 mL microwave reaction vessel equipped with stirbar
  2. customsealed
  3. dry with materialThe organics were dried over anhydrous sodium sulfate
  4. filtrationAfter filtration and solvent removal the residue
  5. customwas purified by reverse phase HPLC (C18, 0-100% CH3CN/water (0.1% TFA))

Sources & evidence

ORD record
ord-fead39208f7b45d7ac2f107ea6454a7d
Source dataset
uspto-grants-2015_06
Patent number
US09050346B2

Reaction notes

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