Potassium Phosphate, Tribasic → 2-(6-Methoxypyridin-3-yl)-5-morpholinoaniline

HRID 1431560Notes

Reaction equation

HRID 1431560 reaction equation
Cl[C:2]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[CH:5][C:3]=1[NH2:4].C1(P(C2CCCCC2)C2(OC)CC=CC(OC)=C2C2C=CC=CC=2)CCCCC1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[CH3:73][O:74][C:75]1[N:80]=[CH:79][C:78](B(O)O)=[CH:77][CH:76]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:73][O:74][C:75]1[N:80]=[CH:79][C:78]([C:2]2[CH:8]=[CH:7][C:6]([N:9]3[CH2:14][CH2:13][O:12][CH2:11][CH2:10]3)=[CH:5][C:3]=2[NH2:4])=[CH:77][CH:76]=1

Participants

9

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 176073522-Chloro-5-(morpholin-4-yl)anilineHCID 665453372-Dicyclohexylphosphino-2,6-dimethoxybiphenyl

Product 1

HCID 596313512-(6-Methoxypyridin-3-yl)-5-morpholinoaniline

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A stirred mixture of 2-chloro-5-morpholinoaniline (608 mg, 2.86 mmol), grounded 2-dicyclohexylphosphino-2,6-dimethoxybiphenyl, (S-Phos) (236 mg, 0.57 mmol), palladium (II) acetate (64.7 mg, 0.29 mmol), 6-methoxypyridin-3-ylboronic acid (876 mg, 5.72 mmol), and potassium phosphate tribasic (1.82 g, 8.59 mmol) in DMF (7.0 mL) and water (0.3 mL) was purged 3 times with argon and placed under vacuum 3 times. The reaction mixture was carefully heated to 90° C. After 21 h, the reaction was cooled to rt, then diluted with water and extracted 3 times with EtOAc. The organic extractions were combined and washed twice with brine. After drying over anhydrous sodium sulfate and filtration, the organic solvent was removed under reduced pressure. The residue was purified over basic alumina (0-20% EtOAc in hexanes) to afford a tan solid as 2-(6-methoxypyridin-3-yl)-5-morpholinoaniline. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.12 (1H, d, J=1.8 Hz), 7.69 (1H, dd, J=8.6, 2.5 Hz), 6.92 (2H, m), 6.34 (1H, d, J=2.3 Hz), 6.28 (1H, dd, J=8.4, 2.5 Hz), 4.68 (2H, s), 3.87 (3H, s), 3.78 (4H, m), 3.12 (4H, m). Mass Spectrum (pos.) m/e: 286.1 (M+1).

Workup

  1. customwas purged 3 times with argon
  2. temperaturethe reaction was cooled to rt
  3. additiondiluted with water
  4. extractionextracted 3 times with EtOAc
  5. extractionThe organic extractions
  6. washwashed twice with brine
  7. dry with materialAfter drying over anhydrous sodium sulfate and filtration
  8. customthe organic solvent was removed under reduced pressure
  9. customThe residue was purified over basic alumina (0-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-9f749b28c6fb4022a99680be0d6419bc
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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