Triethylamine → 7-Chloro-N-[1-(phenylmethyl)-4-piperidinyl]-4-[[4-[[[1-(phenylmethyl)-4-piperidinyl]amino]-carbonyl]phenyl]amino]-3-quinolinecarboxamide

HRID 1755944Notes

Reaction equation

HRID 1755944 reaction equation
N1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=C(C(N)=O)C=1.[Cl:14][C:15]1[CH:24]=[C:23]2[C:18]([C:19]([NH:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]([NH:37][CH:38]4[CH2:43][CH2:42][N:41]([CH2:44][C:45]5[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=5)[CH2:40][CH2:39]4)=[O:36])=[CH:31][CH:30]=3)=[C:20]([C:25]([OH:27])=O)[CH:21]=[N:22]2)=[CH:17][CH:16]=1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C.[NH2:81][CH:82]1[CH2:87][CH2:86][N:85](CC2C=CC=CC=2)[CH2:84][CH2:83]1>CN(C=O)C>[Cl:14][C:15]1[CH:16]=[C:17]2[C:18]([C:19]([NH:28][C:29]3[CH:30]=[CH:31][C:32]([C:35]([NH:37][CH:38]4[CH2:43][CH2:42][N:41]([CH2:44][C:45]5[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=5)[CH2:40][CH2:39]4)=[O:36])=[CH:33][CH:34]=3)=[C:20]([C:25]([NH:81][CH:82]3[CH2:87][CH2:86][N:85]([CH2:4][C:5]4[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=4)[CH2:84][CH2:83]3)=[O:27])[CH:21]=[N:22]2)=[CH:23][CH:24]=1

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 4158521-Benzyl-4-piperidylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 152897637-Chloro-4-[[4-[[[1-(phenylmethyl)-4-piperidinyl]amino]carbonyl]phenyl]amino]-3-quinolinecarboxylic acidHCID 155611013-Quinolinecarboxamide

Product 1

HCID 152897667-Chloro-N-[1-(phenylmethyl)-4-piperidinyl]-4-[[4-[[[1-(phenylmethyl)-4-piperidinyl]amino]-carbonyl]phenyl]amino]-3-quinolinecarboxamideYield 76%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

Step 5, 7-Chloro-N-[1-(phenylmethyl)-4-piperidinyl]-4-[[4-[[[1-(phenylmethyl) -4-piperidinyl]]amino]carbonyl]phenyl]amino]-3-quinolinecarboxamide: 7-Chloro -4-[[4-[[[1-(phenylmethyl)-4-piperidinyl]amino]-carbonyl]phenyl]amino]-3-quinolinecarboxylic acid (2.00 g, 3.88 mmol), 1-hydroxybenzotriazole hydrate (0.640 g, 4.74 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.968 g, 5.05 mmol) were stirred in 22 ml of DMF and treated with triethylamine (1.57 g, 2.2 ml, 15.5 mmol) followed by 4-amino-1-benzylpiperidine (0.813 g, 0.87 ml, 4.27 mmol). The reaction mixture was then heated at 90° C. under nitrogen for 4 h, cooled to room temperature and poured into 250 ml of CH2CH2. The solution was then washed with 3×200 ml of water and concentrated under reduced pressure to a pale beige powder that was dried in vacuo overnight affording 2.037 g (2.96 mmol, 76% yield) of 7-Chloro-N-[1-(phenylmethyl)-4-piperidinyl]-4-[[4-[[[1-(phenylmethyl) -4-piperidinyl]amino]-carbonyl]phenyl]amino]-3-quinolinecarboxamide: mp 230.5°-232° C.; IR (KBr) 3440, 3330, 30 30, 2950, 2800, 1630 cm-1 ; 1H NMR (Me2SO-d6, 400 MHz) δ 9.7 (s, 1 H ), 8.8 (s, 1 H ), 8.39 (d, J=7.5 Hz, 1 H ), 8.11 (d, J=9.1 Hz, 1 H), 8.0 (m, 2 H ), 7.7 (d, J=8.7 Hz, 2 H ), 7.6 (d of d, J=2.2, 9.1 Hz, 1 H ), 7.1-7.35 (m, 10 H ), 6.9 (d, J=8.7 Hz, 2 H ), 3.7 (m, 1 H ), 3.4 (m, 5 H ), 2.74°-2.82 (m, 2 H), 2.64-2.7 (m, 2 H), 1.84-2.04 (m, 4 H ), 1.64°-1.72 (m, 2 H ), 1.46-1.58 (m, 4 H), 1.3-1.4 (m, 2 H ); MS (+DCI, isobutane) m/z (rel intensity)=687 (M+, 100).

Workup

  1. temperaturecooled to room temperature
  2. additionpoured into 250 ml of CH2CH2
  3. washThe solution was then washed with 3×200 ml of water
  4. concentrationconcentrated under reduced pressure to a pale beige powder that
  5. customwas dried in vacuo overnight

Sources & evidence

ORD record
ord-dd729104c35b460e9824ba23b25fa04a
Source dataset
uspto-grants-1995_08
Patent number
US05438064

Reaction notes

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