(2-(4-Methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methanamine → 1-(6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl)-3-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)urea

HRID 571980Notes

Reaction equation

HRID 571980 reaction equation
[N:1]1[CH:6]=[C:5]([NH:7][C:8](=[O:16])OC2C=CC=CC=2)[CH:4]=[C:3]2[CH2:17][CH2:18][CH2:19][C:2]=12.[CH3:20][CH:21]1[CH2:26][CH2:25][N:24]([C:27]2[C:32]([CH2:33][NH2:34])=[CH:31][CH:30]=[C:29]([C:35]([F:38])([F:37])[F:36])[N:28]=2)[CH2:23][CH2:22]1>CN(C=O)C.CN(C1C=CN=CC=1)C>[N:1]1[CH:6]=[C:5]([NH:7][C:8]([NH:34][CH2:33][C:32]2[C:27]([N:24]3[CH2:25][CH2:26][CH:21]([CH3:20])[CH2:22][CH2:23]3)=[N:28][C:29]([C:35]([F:38])([F:36])[F:37])=[CH:30][CH:31]=2)=[O:16])[CH:4]=[C:3]2[CH2:17][CH2:18][CH2:19][C:2]=12

Participants

5

Reactant 2

HCID 58873687(2-(4-Methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methanamineHCID 86676321phenyl 6,7-dihydro-5H-cyclopenta[b]pyridin-3-ylcarbamate

Product 1

HCID 712369681-(6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl)-3-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)ureaYield 77.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of phenyl 6,7-dihydro-5H-cyclopenta[b]pyridin-3-ylcarbamate (E) (80 mg, 0.31 mmol) in DMF was added DMAP (38 mg, 0.31 mmol) and (2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methanamine (F) (90 mg, 0.33 mmol) at room temperature. The reaction mixture was heated to 50° C. for 14 h. TLC showed complete consumption of starting material. The reaction mixture was diluted with water and extracted with EtOAc. The organic part was washed with water and brine. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The crude was purified by column chromatography to give pure 1-(6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl)-3-((2-(4-methylpiperidin-1-yl)-6-(trifluoromethyl)pyridin-3-yl)methyl)urea (example compound I) (104 mg, 76%).

Workup

  1. customconsumption of starting material
  2. additionThe reaction mixture was diluted with water
  3. extractionextracted with EtOAc
  4. washThe organic part was washed with water and brine
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude was purified by column chromatography

Sources & evidence

ORD record
ord-836fbcd10b794bceac3ff41740125201
Source dataset
uspto-grants-2015_05
Patent number
US09029378B2

Reaction notes

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