4-(Piperidin-1-ylmethyl)aniline → 4-[(4-Piperidin-1-ylmethyl-phenylamino)-methylene]-1,4-dihydro-2H-isoquinolin-3-one

HRID 2236637Notes

Reaction equation

HRID 2236637 reaction equation
C[N:2](/[CH:4]=[C:5]1/[C:6](=[O:15])[NH:7][CH2:8][C:9]2[C:14]/1=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH3:3].[N:16]1([CH2:22][C:23]2[CH:28]=[CH:27]C(N)=[CH:25][CH:24]=2)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1>CN(C)C=O>[N:16]1([CH2:22][C:23]2[CH:28]=[CH:27][C:3]([NH:2][CH:4]=[C:5]3[C:14]4[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=4)[CH2:8][NH:7][C:6]3=[O:15])=[CH:25][CH:24]=2)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

4

Reactant 2

HCID 8461504-(Piperidin-1-ylmethyl)anilineHCID 68694591(4E)-4-[(Dimethylamino)methylene]-1,4-dihydro-3(2H)-isoquinolinone

Product 1

HCID 686975404-[(4-Piperidin-1-ylmethyl-phenylamino)-methylene]-1,4-dihydro-2H-isoquinolin-3-oneYield 15.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 0.400 g (1.98 mmol) of (4E)-4-[(Dimethylamino)methylene]-1,4-dihydro-3(2H)-isoquinolinone and 0.300 g (1.58 mmol) of 4-piperidin-1-ylmethyl-phenylamine in 4 mL of N,N-dimethylformamide (DMF) is heated at 125° C. for 3 h. The solvent is removed and the residue is slurried with Et2O and filtered. The Et2O soluble material is evaporated, redissolved in a small volume of PhCH3 and chilled. A precipitate is collected, boiled with MeOH (ca 20 mL) and filtered. The filtrate is evaporated and the residue is recrystallized from a minimum volume of MeOH. The resulting solid is collected, washed with cold MeOH and Et2O and dried in vacuo to yield 0.087 g (13%) of yellow crystals: mp 188-189° C. (dec); 1H NMR (DMSO-d6) δ 11.5 (d, 1H, J=11.8 Hz), 8.04 (d, 1H, J=11.8 Hz), 7.66 (m, 2H), 7.20 (s, 5H), 7.08 (m, 2H), 4.41 (s, 2H), 3.34 (s, 2H), 2.29 (s(br), 4H), 1.46 (m, 6H); HRMS (ESI) m/e calcd for C22H25N3O 348.20704. found 348.20704 (M+H)+1.

Workup

  1. customThe solvent is removed
  2. filtrationfiltered
  3. customThe Et2O soluble material is evaporated
  4. dissolutionredissolved in a small volume of PhCH3
  5. temperaturechilled
  6. customA precipitate is collected
  7. filtrationfiltered
  8. customThe filtrate is evaporated
  9. customthe residue is recrystallized from a minimum volume of MeOH
  10. customThe resulting solid is collected
  11. washwashed with cold MeOH and Et2O
  12. customdried in vacuo

Sources & evidence

ORD record
ord-e2c69c9706254b2c9abf39015e8ed906
Source dataset
uspto-grants-2010_05
Patent number
US07713994B2

Reaction notes

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