4-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline → 5-(5-amino-2-methylphenyl)-1-methyl-3-morpholinopyridin-2(1H)-one

HRID 594084Notes

Reaction equation

HRID 594084 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[CH3:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][C:18]=1B1OC(C)(C)C(C)(C)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>[NH2:21][C:20]1[CH:19]=[CH:18][C:17]([CH3:16])=[C:23]([C:2]2[CH:3]=[C:4]([N:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=2)[CH:22]=1

Participants

6

Reactant 2

HCID 160860894-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 904089385-bromo-1-methyl-3-morpholinopyridin-2(1H)-one

Product 1

HCID 904081725-(5-amino-2-methylphenyl)-1-methyl-3-morpholinopyridin-2(1H)-oneYield 31%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

To a solution of 5-bromo-1-methyl-3-morpholinopyridin-2(1H)-one (1.0 equiv.) and 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1.2 equiv.) in DME and 2M sodium carbonate (3:1, 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 120° C. for 15 min in the microwave. The solution was partitioned between water and ethyl acetate, the organic phase was dried with sodium sulfate, filtered and concentrated. The crude material was purified via silica gel column chromatography eluting with 100% ethyl acetate followed by 10% methanol in ethyl acetate. The pure fractions were concentrated and dried under vacuo to afford 5-(5-amino-2-methylphenyl)-1-methyl-3-morpholinopyridin-2(1H)-one in 31% yield. LCMS (m/z) (M+H)=300.2, Rt=0.41 min.

Workup

  1. customvial equipped with a stir bar
  2. customThe solution was partitioned between water and ethyl acetate
  3. dry with materialthe organic phase was dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified via silica gel column chromatography
  7. washeluting with 100% ethyl acetate
  8. concentrationThe pure fractions were concentrated
  9. customdried under vacuo

Sources & evidence

ORD record
ord-a229ebc32e34438fbf9a1118d1bf94fb
Source dataset
uspto-grants-2016_01
Patent number
US09242969B2

Reaction notes

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