Sodium Carbonate → 4,6-Diamino-2-phenyl-nicotinonitrile

HRID 1364531Notes

Reaction equation

HRID 1364531 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6](Br)[N:5]=[C:4]([NH2:11])[CH:3]=1.[C:12]1(B(O)O)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCCCCC.O.C1COCC1.CN(C=O)C>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:5]=[C:4]([NH2:11])[CH:3]=1

Participants

11

Reactant 4

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 80271Tri-o-tolylphosphineHCID 1706684,6-Diamino-2-bromo-3-pyridinecarbonitrile

Product 1

HCID 669206084,6-Diamino-2-phenyl-nicotinonitrile

Reagents, catalysts & solvents 6

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
130 °C

Procedure

A 5 mL sealable heavy walled glass tube suitable for microwave heating was charged with 213 mg (1.00 mmol) of 4,6-diamino-2-bromo-nicotinonitrile, 183 mg (1.5 mmol) of phenylboronic acid, 11 mg (0.050 mmol) of palladium(II)acetate, 60 mg (0.020 mmol) of tri(o-tolyl)phosphine, and 220 mg (2.05 mmol) of sodium carbonate. To this mixture was added 2 mL of DMF, 2 mL of THF, and 1 mL of water. The tube was sealed, then heated with a microwave apparatus at 130° C. for 20 min. The mixture was poured into 20 mL of water, extracted with ethyl acetate (3×10 mL). The combined ethyl acetate layers were back extracted with 1M NaOH(aq.) (2×10 mL) and brine (1×10 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. The product was partially purified via silica gel chromatography, eluting with 60:40 ethyl acetate:hexanes to provide an off-white solid. This was taken up in ethyl acetate, then hexane was added (until about 50:50 hexanes:ethyl acetate) to precipitate 63 mg (30%) of white crystals. 1H NMR (300 MHz, d6-DMSO) δ 7.66 (m, 2H), 7.45 (m, 3H), 6.35 (s, 2H), 6.25 (s, 2H), 5.69 (s, 1H); MS (ESI) m/e 211 (M+H)+, 209 (M−H)−.

Workup

  1. temperatureA 5 mL sealable heavy walled glass tube suitable for microwave heating
  2. customThe tube was sealed
  3. extractionextracted with ethyl acetate (3×10 mL)
  4. extractionThe combined ethyl acetate layers were back extracted with 1M NaOH(aq.) (2×10 mL) and brine (1×10 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe product was partially purified via silica gel chromatography
  9. washeluting with 60:40 ethyl acetate
  10. customhexanes to provide an off-white solid
  11. customto precipitate 63 mg (30%) of white crystals

Sources & evidence

ORD record
ord-e368652720504e3eb1eeae4581c35985
Source dataset
uspto-grants-2011_02
Patent number
US07888374B2

Reaction notes

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