Triethylamine → N-[1-(Phenylmethyl)-4-piperidinyl]-4-[(4-quinolinylmethyl)amino]benzamide

HRID 248917Notes

Reaction equation

HRID 248917 reaction equation
Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.[N:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:27]([CH2:34][NH:35][C:36]2[CH:44]=[CH:43][C:39]([C:40]([OH:42])=O)=[CH:38][CH:37]=2)=[CH:26][CH:25]=1.C(N(CC)CC)C.[NH2:52][CH:53]1[CH2:58][CH2:57][N:56]([CH2:59][C:60]2[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=2)[CH2:55][CH2:54]1>CN(C)C=O>[C:60]1([CH2:59][N:56]2[CH2:57][CH2:58][CH:53]([NH:52][C:40](=[O:42])[C:39]3[CH:38]=[CH:37][C:36]([NH:35][CH2:34][C:27]4[C:28]5[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=5)[N:24]=[CH:25][CH:26]=4)=[CH:44][CH:43]=3)[CH2:54][CH2:55]2)[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 4158521-Benzyl-4-piperidylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 197624244-[(4-Quinolinylmethyl)amino]benzoic acid

Product 1

HCID 19762443N-[1-(Phenylmethyl)-4-piperidinyl]-4-[(4-quinolinylmethyl)amino]benzamideYield 50.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (3.62 g, 18.9 mmol), 1-hydroxybenzotriazole hydrate (2.43 g, 18.0 mmol), and 4-[(4-quinolinylmethyl)amino]benzoic acid (5.00 g, 18.0 mmol) were placed in a flask under nitrogen. N,N-Dimethylformamide (83 mL) was then added followed by triethylamine (4.5 g, 45 mmol, 6.3 mL) and finally 4-amino-1-benzylpiperidine (3.1 g, 3.3 mL, 16 mmol). The mixture was heated at 100° C. for 45 minutes and the N,N-dimethylformamide was then removed under reduced pressure. The resulting viscous orange oil was triturated overnight with a mixture of 75 mL of water and 50 mL of ethyl acetate with vigorous overhead stirring. The resulting solid was filtered, washed with water and dried under reduced pressure at 60° C. for 25 hours. Flash chromatography on silica gel (65 mm column, 5% ammonia saturated methanol in methylene chloride eluent) afforded fractions containing the product which were concentrated to the point where a white powder formed. The powder was filtered and washed with a small amount of methanol and then ether. Drying under reduced pressure at 60° C. for 19.5 hours afforded 3.65 g (8.1 mmol, 50% yield) of the title compound, m.p. 184°-188° C.

Workup

  1. customthe N,N-dimethylformamide was then removed under reduced pressure
  2. customThe resulting viscous orange oil was triturated overnight with a mixture of 75 mL of water and 50 mL of ethyl acetate with vigorous overhead stirring
  3. filtrationThe resulting solid was filtered
  4. washwashed with water
  5. customdried under reduced pressure at 60° C. for 25 hours
  6. customFlash chromatography on silica gel (65 mm column, 5% ammonia saturated methanol in methylene chloride eluent) afforded fractions
  7. additioncontaining the product which
  8. concentrationwere concentrated to the point where a white powder
  9. customformed
  10. filtrationThe powder was filtered
  11. washwashed with a small amount of methanol
  12. customDrying under reduced pressure at 60° C. for 19.5 hours

Sources & evidence

ORD record
ord-2348625db2a4435a9fad46520e470554
Source dataset
uspto-grants-1993_05
Patent number
US05212182

Reaction notes

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