Morpholine → HCID 59374222, compound

HRID 473614Notes

Reaction equation

HRID 473614 reaction equation
Br[C:2]1[C:3]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N:15]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=3)C(=O)OC(C)(C)C)=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.CC(C)([O-])C.[Na+].[NH:64]1[CH2:69][CH2:68][O:67][CH2:66][CH2:65]1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:67]1[CH2:68][CH2:69][N:64]([C:2]2[C:3]([O:8][C:9]3[CH:10]=[CH:11][C:12]([NH:15][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=4)=[CH:13][CH:14]=3)=[N:4][CH:5]=[CH:6][CH:7]=2)[CH2:65][CH2:66]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 23676156Sodium t-butoxideHCID 67425660HCID 67425660, compound

Product 1

HCID 59374222HCID 59374222, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A microwave reaction vessel was charged with tert-butyl 4-(3-bromopyridin-2-yloxy)phenyl(pyridin-2-yl)carbamate (0.6142 g, 1.39 mmol), palladium (II) acetate (0.0306 g, 0.0833 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (0.0932 g, 0.167 mmol), and sodium tert-butoxide (0.5219 g, 4.17 mmol). The vessel was put under vacuum for 5 min. A solution of morpholine (0.316 mL, 2.78 mmol) in toluene was added to the vessel. The reaction was allowed to heat at 90° C. for 10 min. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage™ pre-packed silica gel column (40M), eluting with a gradient of 10% to 50% acetone in hexane. Product was taken up in DCM and TFA was added to stir overnight. The solvent was removed and the residue was filtered through a carbonate filter to provide N-(4-(3-morpholinopyridin-2-yloxy)phenyl)pyridin-2-amine. MS (ESI, pos. ion) m/z: 349.1 (M+1). IC50 (uM) 0.030207.

Workup

  1. customA microwave reaction vessel
  2. customchromatographed through a Biotage™ pre-packed silica gel column (40M)
  3. washeluting with a gradient of 10% to 50% acetone in hexane
  4. additionTFA was added
  5. customThe solvent was removed
  6. filtrationthe residue was filtered through a carbonate
  7. filtrationfilter

Sources & evidence

ORD record
ord-77759c5d851046b39ac97c20a8b4199a
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

Loading…