Dimethylformamide → 3-(2-Oxo-1,2,4,5-tetrahydroimidazo[1,5,4-de][1,4]benzoxazin-4-yl)pyridine-2-carbonitrile

HRID 589105Notes

Reaction equation

HRID 589105 reaction equation
Br[C:2]1[C:7]([CH:8]2[N:13]3[C:14](=[O:20])[NH:15][C:16]4=[CH:17][CH:18]=[CH:19][C:11](=[C:12]34)[O:10][CH2:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:21][N:22](C)C=O>C(OCC)(=O)C.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[O:20]=[C:14]1[N:13]2[CH:8]([C:7]3[C:2]([C:21]#[N:22])=[N:3][CH:4]=[CH:5][CH:6]=3)[CH2:9][O:10][C:11]3=[C:12]2[C:16](=[CH:17][CH:18]=[CH:19]3)[NH:15]1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 904093524-(2-bromopyridin-3-yl)-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-one

Product 1

HCID 904098963-(2-Oxo-1,2,4,5-tetrahydroimidazo[1,5,4-de][1,4]benzoxazin-4-yl)pyridine-2-carbonitrile

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
160 °C

Procedure

A suspension of 4-(2-bromopyridin-3-yl)-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-one (964 mg, 2.90 mmol), zinc cyanide (1.00 g, 8.70 mmol) and tetrakis(triphenylphosphine)palladium(0) (335 mg, 0.290 mmol) in N,N-dimethylformamide (20.4 mL) was degassed and heated in a microwave at 160° C. for 20 min. The reaction mixture was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate, water and brine, dried over magnesium sulfate, filtered, and concentrated to give the crude product. The crude product was suspended in hot ethyl acetate and diluted with hexanes to twice the volume, which resulted in the precipitation of a solid. The solid was collected by filtration and washed with ethyl acetate to give the desired product (656 mg). The filtrate was concentrated to a residue which was purified by preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product that was combined with the precipitated material (0.709 g total, 88% combined yield) as a racemic mixture. LCMS calculated for C15H11N4O2 (M+H)+: m/z=279.1. found: 278.9.

Workup

  1. customwas degassed
  2. additionThe reaction mixture was diluted with ethyl acetate
  3. washwashed with saturated aqueous sodium bicarbonate, water and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude product
  8. customresulted in the precipitation of a solid
  9. filtrationThe solid was collected by filtration
  10. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-fabc5a73c93a4ddba0945eab4708f0a3
Source dataset
uspto-grants-2016_01
Patent number
US09227985B2

Reaction notes

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