Potassium Carbonate → HCID 67497890, compound

HRID 1628275Notes

Reaction equation

HRID 1628275 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH2:8])[CH:3]=1.O.[NH2:10][C:11]1[CH:12]=[C:13](B(O)O)[CH:14]=[CH:15][CH:16]=1.C([O-])([O-])=O.[K+].[K+]>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.CN(C=O)C>[NH2:10][C:11]1[CH:16]=[C:15]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([NH2:8])[CH:3]=2)[CH:14]=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 6932822-Amino-4-bromopyridineHCID 143894233-Aminophenylboronic acid monohydrate

Product 1

HCID 67497890HCID 67497890, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a 100 ml flask was added 4-bromopyridin-2-amine 36.A (432 mg, 2.50 mmol, available from Apollo), 3-aminophenylboronic acid hydrate 36.B (465 mg, 3.00 mmol, available from Oakwood), tetrakis(triphenylphosphine)palladium(0) (288 mg, 0.25 mmol), DMF (5 mL) and saturated aqueous K2CO3 (5 mL). The reaction mixture was stirred at 80° C. overnight. The reaction was then extracted with DCM (2×50 mL), the organic layers combined, washed with brine and dried on MgSO4. The DCM was removed under vacuum, leaving a crude solution of 4-(3-aminophenyl)pyridin-2-amine in DMF to which was added more DMF (10 mL), (S)-2-(tert-butoxycarbonyl)-3-phenylpropanoic acid (662 mg, 2.5 mmol, available from Aldrich), diisopropylethylamine (1.74 mL, 10 mmol) and 2-(1H-Benzotriazole-1-yl)-1,1,3,3-Tetramethyluronium hexafluorophosphate (1.90 g, 5.0 mmol). The resulting mixture was stirred overnight at room temperature. The mixture was then partitioned between water (50 mL) and EtOAc (100 mL). The layers were separated, and the aqueous phase was extracted with additional EtOAc (2×50 mL). The combined organic layers were washed with water and brine, dried (MgSO4), and concentrated. The residue was purified by silica gel flash chromatography to afford tert-butyl (S)-1-(3-(2-aminopyridin-4-yl)phenylamino)-1-oxo-3-phenylpropan-2-ylcarbamate 36.C (200 mg, 15% yield).

Workup

  1. extractionThe reaction was then extracted with DCM (2×50 mL)
  2. washwashed with brine
  3. customdried on MgSO4
  4. customThe DCM was removed under vacuum

Sources & evidence

ORD record
ord-af51556e236944eaac6178d5ff03e579
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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