Morpholine → 6'-Methoxy-5-morpholino-2,3'-bipyridin-3-amine

HRID 1431565Notes

Reaction equation

HRID 1431565 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH2:16])[C:5]([C:8]2[CH:9]=[N:10][C:11]([O:14][CH3:15])=[CH:12][CH:13]=2)=[N:6][CH:7]=1.[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH3:15][O:14][C:11]1[N:10]=[CH:9][C:8]([C:5]2[C:4]([NH2:16])=[CH:3][C:2]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:7][N:6]=2)=[CH:13][CH:12]=1

Participants

9

Reactant 5

HCID 8083MorpholineHCID 2733832Lithium HexamethyldisilazideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596314045-Bromo-6'-methoxy-2,3'-bipyridin-3-amineHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

Product 1

HCID 596314166'-Methoxy-5-morpholino-2,3'-bipyridin-3-amine

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

A mixture of 5-bromo-6′-methoxy-2,3′-bipyridin-3-amine (711 mg, 2.54 mmol), morpholine (1.1 mL, 12.63 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropyl-biphenyl, (X-Phos) (97.7 mg, 0.21 mmol), and tris(dibenzylideneacetone)-dipalladium (0) (93.8 mg, 0.102 mmol) in dry THF (6.0 mL) was degassed by nitrogen. To this mixture was added lithium bis(trimethylsilyl)amide, 1.0M in THF (14.0 mL, 14.0 mmol) dropwise, and the resulting reaction was heated to 60° C. After 2.5 h, the reaction was cooled to rt then poured into water. After extracting twice with EtOAc and twice with DCM, the combined organic layers were dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on silica gel (0-60% of 89:9:1 DCM:MeOH:ammonium hydroxide in DCM) to afford an orange tan solid as 6′-methoxy-5-morpholino-2,3′-bipyridin-3-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.46 (1H, dd, J=2.4, 0.7 Hz), 7.90 (2H, m), 6.83 (1H, dd, J=8.6, 0.8 Hz), 6.53 (1H, d, J=2.5 Hz), 3.97 (3H, s), 3.89 (4H, m), 3.78 (2H, s), 3.21 (4H, m). Mass Spectrum (pos.) m/e: 287.0 (M+1).

Workup

  1. customwas degassed by nitrogen
  2. customthe resulting reaction
  3. temperaturethe reaction was cooled to rt
  4. extractionAfter extracting twice with EtOAc and twice with DCM
  5. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
  6. filtrationAfter filtration and concentration
  7. customthe residue was purified on silica gel (0-60% of 89:9:1 DCM:MeOH:ammonium hydroxide in DCM)

Sources & evidence

ORD record
ord-9bcff6962d234364bfc5c7408391776b
Source dataset
uspto-grants-2015_01
Patent number
US08940724B2

Reaction notes

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