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

HRID 2170234Notes

Reaction equation

HRID 2170234 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1B(O)O.CC12CC3(C)P(C4C=CC=CC=4)C(C)(CC(C)(O3)O1)O2.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:43]1[N:44]([CH2:54][O:55][CH2:56][CH2:57][Si:58]([CH3:61])([CH3:60])[CH3:59])[C:45]([CH3:53])=[C:46]2[C:51]=1[CH2:50][CH2:49][NH:48][C:47]2=[O:52].CC1NC(=O)C2C(=C(C3C=CC=CC=3OC3C=CC=CC=3)NC=2C)N=1.[Cl-].[Na+]>C(OCC)(=O)C.O1CCOCC1.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[C:43]1[N:44]([CH2:54][O:55][CH2:56][CH2:57][Si:58]([CH3:59])([CH3:61])[CH3:60])[C:45]([CH3:53])=[C:46]2[C:51]=1[CH2:50][CH2:49][NH:48][C:47]2=[O:52]

Participants

9

Reactant 6

HCID 5234Sodium ChlorideHCID 62657Potassium Phosphate, TribasicHCID 2763280(2-Fluoro-5-nitrophenyl)boronic acidHCID 534277901,3,5,7-Tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantaneHCID 90387110HCID 90387110, compoundHCID 1365969572,5-dimethyl-7-(2-phenoxyphenyl)-3,6-dihydro-4H-pyrrolo[3,4-d]pyrimidin-4-one

Product 1

HCID 903871851-(2-fluoro-5-nitrophenyl)-3-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-6,7-dihydro-2H-pyrrolo[3,4-c]pyridin-4(5H)-one

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

2-fluoro-5-nitrophenylboronic acid (0.134 g, 0.725 mmol), tris(dibenzylidineacetone)dipalladium(0) (0.0157 g, 0.017 mmol), 1,3,5,7-tetramethyl-6-phenyl-2,4,8-trioxa-6-phosphaadamantane (0.0165 g, 0.056 mmol) and tris-potassium phosphate (0.280 g, 1.319 mmol) were combined in a sealed 5 mL microwave tube with stir bar and sparged with nitrogen for 15 minutes. A solution of Example 93g (0.173 g, 0.481 mmol) in a degassed mixture of 4:1 dioxane/water (5.0 mL) was added by syringe into the reaction vessel which was heated at 110° C. for 25 minutes in a Biotage Initiator 2 monomode microwave reactor, then cooled to ambient temperature. The reaction mixture was shaken in a separatory funnel with 75 mL ethyl acetate and 40 mL saturated aqueous sodium chloride. The organics were dried over anhydrous sodium sulfate. Filtration and solvent removal gave a yellow oil which was chromatographed on a 40 g silica gel cartridge eluting with 0-100% ethyl acetate/heptane to provide the title compound.

Workup

  1. customsparged with nitrogen for 15 minutes
  2. additionwas added by syringe into the reaction vessel which
  3. dry with materialThe organics were dried over anhydrous sodium sulfate
  4. filtrationFiltration and solvent removal
  5. customgave a yellow oil which
  6. customwas chromatographed on a 40 g silica gel cartridge
  7. washeluting with 0-100% ethyl acetate/heptane

Sources & evidence

ORD record
ord-705f2703b7cf4467a88ce1e39e5c83c5
Source dataset
uspto-grants-2015_06
Patent number
US09050346B2

Reaction notes

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