1-(1-Phenylethyl)piperazine → 2-chloro-N,N-dimethyl-5-(4-(4-(1-phenylethyl)-1-piperazinyl)-6-quinolinyl)-3-pyridinamine

HRID 1963789Notes

Reaction equation

HRID 1963789 reaction equation
[Cl:1][C:2]1[C:7]([N:8]([CH3:10])[CH3:9])=[CH:6][C:5]([C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[N:17]=[CH:16][CH:15]=[C:14]3Cl)=[CH:4][N:3]=1.[C:22]1([CH:28]([N:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[CH3:29])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CS(C)=O>[Cl:1][C:2]1[C:7]([N:8]([CH3:10])[CH3:9])=[CH:6][C:5]([C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[N:17]=[CH:16][CH:15]=[C:14]3[N:33]2[CH2:34][CH2:35][N:30]([CH:28]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH3:29])[CH2:31][CH2:32]2)=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 27371341-(1-Phenylethyl)piperazineHCID 446101612-chloro-5-(4-chloro-6-quinolinyl)-N,N-dimethyl-3-pyridinamine

Product 1

HCID 446103152-chloro-N,N-dimethyl-5-(4-(4-(1-phenylethyl)-1-piperazinyl)-6-quinolinyl)-3-pyridinamineYield 70.6%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
110 °C

Procedure

(Some starting materials may be obtained from Chess GmbH, Mannnheim, Germany) To a microwave vial (5 mL), 2-chloro-5-(4-chloroquinolin-6-yl)-N,N-dimethylpyridin-3-amine (0.0846 g, 0.266 mmol) and 1-(1-phenylethyl)-piperazine (0.125 mL, 0.665 mmol) were added into DMSO (4 mL). The mixture was stirred at 90 oC for 2.5 h, at 110° C. for 3 h, then at RT for overnight. The reaction was partitioned between water (20 mL) and EtOAc (20 mL). The aqueous phase was extracted with EtOAc (2×20 mL). The combined organic phases were washed with saturated aqueous NaCl (40 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (eluent: acetone in hexanes 0% -50%) to afford the title compound as a white solid (0.0886 g). m/z: calc'd for C28H30ClN5; 471.2, found: 472.2 (M+1). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.46 (d, J=6.6 Hz, 3 H), 2.63-2.89 (m, 4 H), 2.94 (s, 6 H), 3.29 (t, J=4.4 Hz, 4 H), 3.51 (d, J=6.7 Hz, 1 H), 6.88 (d, J=5.0 Hz, 1 H), 7.28-7.42 (m, 5 H), 7.56 (d, J=2.2 Hz, 1 H), 7.84 (dd, J=8.7, 2.1 Hz, 1 H), 8.10-8.20 (m, 2 H), 8.33 (d, J=2.2 Hz, 1 H), 8.75 (d, J=5.0 Hz, 1 H).

Workup

  1. waitat RT for overnight
  2. customThe reaction was partitioned between water (20 mL) and EtOAc (20 mL)
  3. extractionThe aqueous phase was extracted with EtOAc (2×20 mL)
  4. washThe combined organic phases were washed with saturated aqueous NaCl (40 mL)
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by column chromatography (eluent: acetone in hexanes 0% -50%)

Sources & evidence

ORD record
ord-896d1d79f84b42dcb0716d3612b48ad2
Source dataset
uspto-grants-2013_04
Patent number
US08415376B2

Reaction notes

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