Triethylamine → 2-ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-6-morpholin-4-yl-4-(trifluoromethyl)-pyridine-3-carboxylic acid amide

HRID 1039751Notes

Reaction equation

HRID 1039751 reaction equation
[CH2:1]([S:3][C:4]1[C:9]([C:10](O)=[O:11])=[C:8]([C:13]([F:16])([F:15])[F:14])[CH:7]=[C:6]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[N:5]=1)[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.[F:54][C:55]1[CH:56]=[C:57]([CH:60]=[CH:61][CH:62]=1)[CH2:58][NH2:59]>C1COCC1>[CH2:1]([S:3][C:4]1[C:9]([C:10]([NH:59][CH2:58][C:57]2[CH:60]=[CH:61][CH:62]=[C:55]([F:54])[CH:56]=2)=[O:11])=[C:8]([C:13]([F:15])([F:14])[F:16])[CH:7]=[C:6]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[N:5]=1)[CH3:2]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 668533-FluorobenzylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672876242-(Ethylsulfanyl)-6-morpholin-4-yl-4-(trifluoromethyl)-pyridine-3-carboxylic acid

Product 1

HCID 569627642-ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-6-morpholin-4-yl-4-(trifluoromethyl)-pyridine-3-carboxylic acid amideYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 170 mg (0.5 mmol) 2-(ethylsulfanyl)-6-morpholin-4-yl-4-(trifluoromethyl)-pyridine-3-carboxylic acid in THF (3 ml) were added 192 mg (0.5 mmol) HATU and 210 μl (1.5 mmol) NEt3 and the RM was stirred at 50° C. for 90 min. Then 69 μl (0.6 mmol) 3-fluorobenzylamine were added and stirring was continued at 50° C. for 5 d. After cooling to RT the mixture was partitioned between water and EtOAc. The organic layer was separated, washed with a 4N aq. NH4Cl sol. and brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by CC (hexane/EtOAc 3:1) provided 57 mg (0.13 mmol, 26%) 2-ethylsulfanyl-N-[(3-fluorophenyl)-methyl]-6-morpholin-4-yl-4-(trifluoromethyl)-pyridine-3-carboxylic acid amide (example 11). [M+H]+ 444.1.

Workup

  1. stirringstirring
  2. waitwas continued at 50° C. for 5 d
  3. temperatureAfter cooling to RT the mixture
  4. customwas partitioned between water and EtOAc
  5. customThe organic layer was separated
  6. washwashed with a 4N aq. NH4Cl sol. and brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by CC (hexane/EtOAc 3:1)

Sources & evidence

ORD record
ord-afbad1764c944bb898494f5e98edadd4
Source dataset
uspto-grants-2013_10
Patent number
US08552200B2

Reaction notes

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