1,2-Dichloroethane → N-(3-(4-(5-chloro-2-methylphenyl)piperazin-1-yl)propyl)-6,6a,7,8,9,10-hexahydro-6-oxo-5H-pyrido[1,2-a]quinoxaline-3-carboxamide

HRID 576507Notes

Reaction equation

HRID 576507 reaction equation
[O:1]=[C:2]1[NH:11][C:10]2[CH:9]=[C:8]([C:12]([OH:14])=O)[CH:7]=[CH:6][C:5]=2[N:4]2[CH2:15][CH2:16][CH2:17][CH2:18][CH:3]12.[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([CH3:36])=[C:24]([N:26]2[CH2:31][CH2:30][N:29]([CH2:32][CH2:33][CH2:34][NH2:35])[CH2:28][CH2:27]2)[CH:25]=1.CCN(C(C)C)C(C)C.C(Cl)CCl>CN(C1C=CN=CC=1)C.CN(C=O)C>[Cl:19][C:20]1[CH:21]=[CH:22][C:23]([CH3:36])=[C:24]([N:26]2[CH2:27][CH2:28][N:29]([CH2:32][CH2:33][CH2:34][NH:35][C:12]([C:8]3[CH:7]=[CH:6][C:5]4[N:4]5[CH2:15][CH2:16][CH2:17][CH2:18][CH:3]5[C:2](=[O:1])[NH:11][C:10]=4[CH:9]=3)=[O:14])[CH2:30][CH2:31]2)[CH:25]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 433253696-oxo-6,6a,7,8,9,10-hexahydro-5H-pyrido[1,2-a]quinoxaline-3-carboxylic acidHCID 441227473-[4-(5-Chloro-2-methylphenyl)piperazin-1-yl]propan-1-amine

Product 1

HCID 20966565N-(3-(4-(5-chloro-2-methylphenyl)piperazin-1-yl)propyl)-6,6a,7,8,9,10-hexahydro-6-oxo-5H-pyrido[1,2-a]quinoxaline-3-carboxamideYield 1,582.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 6,6a,7,8,9,10-hexahydro-6-oxo-5H-pyrido[1,2-a]quinoxaline-3-carboxylic acid (200 mg, 0.80 mmole), 3-(4-(5-chloro-2-methylphenyl)piperazin-1-yl)propan-1-amine (1.0 mmol), DMAP (10 mg) and DIPEA (0.30 mL) in DMF (5 mL) was added EDC (0.377 g, 2.0 mmole). The reaction solution was stirred at room temperature overnight. The solvent removed and EtOAc (60 mL) was added. The organic layer was washed with saturated sodium bicarbonate (10 mL), water (10 mL) and dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified by column chromatography with 0-10% methanol in dichloromethane to provide the N-(3-(4-(5-chloro-2-methylphenyl)piperazin-1-yl)propyl)-6,6a,7,8,9,10-hexahydro-6-oxo-5H-pyrido[1,2-a]quinoxaline-3-carboxamide as white solid (6.28 g, 78%). 1HNMR (300 MHz, dmso-d6), ppm: 10.48 (s, 1 H), 8.27 (t, 1 H), 7.41 (dd, 1 H), 7.29 (d, 1 H), 7.15 (d, 1 H), 6.97 (d, 1 H), 6.96 (s, 1 H), 6.83 (d, 1 H), 3.83 (d, 1 H), 3.57 (dd, 1 H), 3.26 (q, 2 H), 2.84 (m, 4 H), 2.73 (dt, 1 H), 2.40 (t, 2 H), 2.20 (s, 3 H), 2.00 (m, 1 H), 1.83 (m, 1 H), 1.69 (m, 3 H), 1.52-1.33 (m, 3 H). MS (ESI+) M/z: 496, 498 (M+H).

Workup

  1. customThe solvent removed
  2. additionEtOAc (60 mL) was added
  3. washThe organic layer was washed with saturated sodium bicarbonate (10 mL), water (10 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationAfter filtration and concentration
  6. customthe residue was purified by column chromatography with 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-459c9a44f6934a6181d8336a339e1109
Source dataset
uspto-grants-2015_05
Patent number
US09040508B2

Reaction notes

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