Morpholine → N-methyl-6-morpholin-4-yl-4-o-tolyl-nicotinamide

HRID 352322Notes

Reaction equation

HRID 352322 reaction equation
Cl[C:2]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH3:18])[C:5]([C:6]([NH:8][CH3:9])=[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)C(C)C)C>CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[CH3:9][NH:8][C:6](=[O:7])[C:5]1[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[CH3:18])=[CH:11][C:2]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[N:3][CH:4]=1

Participants

6

Reactant 3

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 121673126-chloro-N-methyl-4-o-tolyl-nicotinamide

Product 1

HCID 22479279N-methyl-6-morpholin-4-yl-4-o-tolyl-nicotinamideYield 92.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 1.00 g (3.84 mmol) 6-chloro-N-methyl-4-o-tolyl-nicotinamide, 0.37 ml (4.22 mmol) morpholine, 2.0 ml (12 mmol) N-ethyldiisopropylamine and a catalytic amount of 4-(N,N-dimethylamino)-pyridine was heated at 100° C. over night. After cooling to room temperature the mixture was dissolved in ethyl acetate and washed with two portions of water. The combined aqueous layers were extracted with 3 portions of dichloromethane. Drying with sodium sulfate and concentration gave 1.23 g of the crude product. Flash column chromatography afforded 1.11 g (92.9%) of the title compound as an off-white solid. M.p. 156-158° C.

Workup

  1. washwashed with two portions of water
  2. extractionThe combined aqueous layers were extracted with 3 portions of dichloromethane
  3. dry with materialDrying with sodium sulfate and concentration
  4. customgave 1.23 g of the crude product

Sources & evidence

ORD record
ord-7d5b477a823d4d07ad33929d6b8026be
Source dataset
uspto-grants-2004_06
Patent number
US06747026B2

Reaction notes

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