Triethylamine → N-[(3,5-difluoro-phenyl)-methyl]-2-ethylsulfanyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide

HRID 1753850Notes

Reaction equation

HRID 1753850 reaction equation
[CH2:1]([S:3][C:4]1[C:9]([C:10]([OH:12])=O)=[C:8]([CH3:13])[CH:7]=[C:6]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[N:5]=1)[CH3:2].[F:20][C:21]1[CH:22]=[C:23]([CH:26]=[C:27]([F:29])[CH:28]=1)[CH2:24][NH2:25].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>C1COCC1.CCOC(C)=O>[F:20][C:21]1[CH:22]=[C:23]([CH2:24][NH:25][C:10]([C:9]2[C:4]([S:3][CH2:1][CH3:2])=[N:5][C:6]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)=[CH:7][C:8]=2[CH3:13])=[O:12])[CH:26]=[C:27]([F:29])[CH:28]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 1452113,5-DifluorobenzylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672874632-Ethylsulfanyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid

Product 1

HCID 56962683N-[(3,5-difluoro-phenyl)-methyl]-2-ethylsulfanyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amideYield 52%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 250 mg (0.89 mmol) 2-ethylsulfanyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid in THF (7 ml), 124 μl (0.97 mmol) 3,5-difluorobenzylamine, 335 mg (0.89 mmol) HATU and 367 μl (2.66 mmol) NEt3 were added and the RM was heated at 70° C. for 5d. Subsequently the mixture was diluted with EtOAc and washed with a 4M aq. NH4Cl sol., a 1M aq. NaHCO3 sol. and brine. The organic layer was dried over MgSO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 3:2) provided 187 mg (0.46 mmol, 52%) N-[(3,5-difluoro-phenyl)-methyl]-2-ethylsulfanyl-4-methyl-6-morpholin-4-yl-pyridine-3-carboxylic acid amide (example 1). [M+H]+408.1.

Workup

  1. washwashed with a 4M aq. NH4Cl sol.
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customPurification of the residue by CC (hexane/EtOAc 3:2)

Sources & evidence

ORD record
ord-59d06ca20b0f41d698daac6615ba2dae
Source dataset
uspto-grants-2015_10
Patent number
US09168259B2

Reaction notes

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