Morpholine → N-(3-Iodo-4-methyl-phenyl)-6-morpholin-4-yl-nicotinamide

HRID 2190558Notes

Reaction equation

HRID 2190558 reaction equation
Cl[C:2]1[CH:18]=[CH:17][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[C:11]([I:16])[CH:10]=2)=[O:7])=[CH:4][N:3]=1.[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.C(N(C(C)C)CC)(C)C>CN(C1C=CN=CC=1)C.O1CCOCC1>[I:16][C:11]1[CH:10]=[C:9]([NH:8][C:6](=[O:7])[C:5]2[CH:17]=[CH:18][C:2]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[N:3][CH:4]=2)[CH:14]=[CH:13][C:12]=1[CH3:15]

Participants

6

Reactant 3

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 79255626-chloro-N-(3-iodo-4-methyl-phenyl)-nicotinamide

Product 1

HCID 17541675N-(3-Iodo-4-methyl-phenyl)-6-morpholin-4-yl-nicotinamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 6-chloro-N-(3-iodo-4-methyl-phenyl)-nicotinamide (50 mg, 0.13 mmol) and morpholine (35 mg, 0.42 mmol), diisopropylethyl amine (0.07 mL, 0.42 mmol) and a catalytic amount of DMAP in dioxane (5 mL) was heated at 120° C. in a sealed tube until consumption of the limiting reagent. The mixture was then cooled and partitioned between EtOAc and water. Organic layer was removed, dried over Na2SO4 filtered and concentrated to a residue that after a silica gel column with 20-40% EtOAc in hexanes gradient afforded the product. HRMS m/z calcd for C17H18N3O2I [M+H]+: 424.0517. Found: 424.0516.

Workup

  1. temperatureThe mixture was then cooled
  2. custompartitioned between EtOAc and water
  3. customOrganic layer was removed
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to a residue that after a silica gel column with 20-40% EtOAc in hexanes gradient
  7. customafforded the product

Sources & evidence

ORD record
ord-f286f29b0c4d4e45999e1ba142c09410
Source dataset
uspto-grants-2012_12
Patent number
US08324385B2

Reaction notes

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