Triethylamine → [3-Methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

HRID 1517072Notes

Reaction equation

HRID 1517072 reaction equation
[CH3:1][C:2]1[C:3]([C:18]([OH:20])=O)=[N:4][CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[CH:7]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CCN(CC)CC.[N:52]1([CH:57]2[CH2:62][CH2:61][NH:60][CH2:59][CH2:58]2)[CH2:56][CH2:55][CH2:54][CH2:53]1>CN(C=O)C>[CH3:1][C:2]1[C:3]([C:18]([N:60]2[CH2:61][CH2:62][CH:57]([N:52]3[CH2:56][CH2:55][CH2:54][CH2:53]3)[CH2:58][CH2:59]2)=[O:20])=[N:4][CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:15])([F:16])[F:17])[CH:9]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 787034-(1-Pyrrolidinyl)piperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 574411243-Methyl-5-(3-trifluoromethyl-phenyl)-pyridine-2-carboxylic acid2×

Product 1

HCID 44547210[3-Methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanoneYield 89.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 0.42 g (1.5 mmol) of 3-methyl-5-(3-trifluoromethyl-phenyl)-pyridine-2-carboxylic acid (intermediate 1B) in 15 ml of DMF was added 0.60 g (1.6 mmol) of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) and 0.62 ml=0.45 g (4.5 mmol) of Et3N; after 30 min, 0.24 g (1.6 mmol) of 4-pyrrolidin-1-yl-piperidine was added. 1 hour later, the reaction mixture was poured into crashed ice and extracted three times with EtOAc; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 95:5 to 4:1) to give 0.56 g (89%) of the title compound as light brown oil. MS: 418.1 (MH+).

Workup

  1. addition1 hour later, the reaction mixture was poured
  2. extractionextracted three times with EtOAc
  3. washthe organic phases were washed with water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 95:5 to 4:1)

Sources & evidence

ORD record
ord-3d072fbb189446e1b6dfa0981cd840c8
Source dataset
uspto-grants-2012_07
Patent number
US08227613B2

Reaction notes

Loading…