Potassium Phosphate, Tribasic → HCID 69708574, compound

HRID 2183887Notes

Reaction equation

HRID 2183887 reaction equation
Br[C:2]1[N:6]2[CH:7]=[CH:8][C:9]([CH:11]([O:14][CH3:15])[O:12][CH3:13])=[N:10][C:5]2=[N:4][CH:3]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[F:24][C:25]1[CH:30]=[CH:29][C:28](B2OC(C)(C)C(C)(C)O2)=[CH:27][C:26]=1[C:40]1[C:41]([C:46]#[N:47])=[CH:42][CH:43]=[CH:44][CH:45]=1>CN(C)C=O.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>[CH3:13][O:12][CH:11]([O:14][CH3:15])[C:9]1[CH:8]=[CH:7][N:6]2[C:2]([C:28]3[CH:29]=[CH:30][C:25]([F:24])=[C:26]([C:40]4[C:41]([C:46]#[N:47])=[CH:42][CH:43]=[CH:44][CH:45]=4)[CH:27]=3)=[CH:3][N:4]=[C:5]2[N:10]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 117716472′-Fluoro-5′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)[1,1′-biphenyl]-2-carbonitrileHCID 18001285HCID 18001285, compound

Product 1

HCID 69708574HCID 69708574, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-bromo-7-dimethoxymethylimidazo[1,2-α]pyrimidine (1.36 g, 5 mmol), potassium phosphate (2.12 g, 10 mmol), 2′-fluoro-5′-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)biphenyl-2-carbonitrile (2.42 g, 7.5 mmol) and tetrakis(triphenylphosphine)palladium(0) (230 mg, 0.2 mmol) in N,N-dimethylformamide (15 ml) was heated at 80° C. for 14 h. The reaction was cooled and partitioned between ethyl acetate and water. The organics were washed with water, brine, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness to afford crude 5′-(7-dimethoxymethylimidazo[1,2-α]pyrimidin-3-yl)-2′-fluorobiphenyl-2-carbonitrile. The residue was suspended in 1,4-dioxane (30 ml) then treated with 3N hydrochloric acid (30 ml) and this mixture was heated at 60° C. for 14 h. The reaction was cooled and partitioned between dichloromethane and water. The organics were washed with water, brine, dried over anhydrous magnesium sulfate, filtered and pre-adsorbed onto silica. Purification by chromatography on silica gel eluting with dichloromethane (+1% triethylamine) on a gradient of methanol (1-4%) gave a solid. Trituration with ether afforded 2′-fluoro-5′-(7-formylimidazo[1,2-α]pyrimidin-3-yl)biphenyl-2-carbonitrile as a yellow powder (1.2 g, 70% over 2 steps): δH (400 MHz, DMSO) 7.48 (1H, d, J 7), 7.65-7.72 (2H, m), 7.75-7.80 (1H, m), 7.87 (1H, ddd, J 8, 8 and 1), 7.95-7.99 (2H, m), 8.02-8.05 (1H, m), 8.40 (1H, s), 9.27 (1H, dd, J 7 and 1), 9.96 (1H, s); m/z (ES+) 343 (M++H).

Workup

  1. temperatureThe reaction was cooled
  2. custompartitioned between ethyl acetate and water
  3. washThe organics were washed with water, brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated to dryness

Sources & evidence

ORD record
ord-82baec45e51a43a7ad9fb65acdeef202
Source dataset
uspto-grants-2005_05
Patent number
US06900215B2

Reaction notes

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