5-Bromo-6-methylpyridin-3-amine → 2-Methyl-2'-morpholino-[3,4'-bipyridin]-5-amine

HRID 594067Notes

Reaction equation

HRID 594067 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH2:9])[CH:5]=[N:6][C:7]=1[CH3:8].CC1(C)C(C)(C)OB([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[CH:19]=2)O1>COCCOC.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH3:8][C:7]1[C:2]([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([N:24]3[CH2:25][CH2:26][O:27][CH2:28][CH2:29]3)[CH:19]=2)=[CH:3][C:4]([NH2:9])=[CH:5][N:6]=1

Participants

6

Reactant 2

HCID 184588965-Bromo-6-methylpyridin-3-amineHCID 210816614-(4-(Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)morpholine

Product 1

HCID 904086172-Methyl-2'-morpholino-[3,4'-bipyridin]-5-amine

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 5-bromo-6-methylpyridin-3-amine (1.0 equiv.) and 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)morpholine (1.7 equiv.) in DME and 2M sodium carbonate (4:1, 0.14 M) was added PdCl2(dppf)-DCM adduct (0.1 equiv.) in a microwave vial equipped with a stir bar. The reaction was heated to 110° C. for 15 min in the microwave. The cooled reaction mixture was partitioned between water and ethyl acetate. The organic phase was dried with sodium sulfate, filtered and concentrated. The crude material was purified by flash chromatography over silica gel (DCM with a 0-20% methanol gradient). The pure fractions were concentrated in vacuo to afford 2-methyl-2′-morpholino-[3,4′-bipyridin]-5-amine in quantitative yield. LCMS (m/z) (M+H)=271.1, Rt=0.26 min.

Workup

  1. customvial equipped with a stir bar
  2. customThe cooled reaction mixture
  3. customwas partitioned between water and ethyl acetate
  4. dry with materialThe organic phase was dried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by flash chromatography over silica gel (DCM with a 0-20% methanol gradient)
  8. concentrationThe pure fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-5054853f24dc45b09b0cf3dbe3fac5f4
Source dataset
uspto-grants-2016_01
Patent number
US09242969B2

Reaction notes

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