N-methyl-2-pyrrolidone → HCID 10055074, compound

HRID 1354799Notes

Reaction equation

HRID 1354799 reaction equation
[O:1]=[C:2]1[N:6]([CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]4[C:21]([C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=5)=[N:22][C:23]5[C:28]([N:29]=4)=[CH:27][C:26]([C:30](O)=[O:31])=[CH:25][CH:24]=5)=[CH:16][CH:15]=3)[CH2:9][CH2:8]2)[C:5]2[CH:39]=[CH:40][CH:41]=[CH:42][C:4]=2[NH:3]1.C1C=CC2N(O)N=NC=2C=1.N=C=N.[CH2:56]([N:58]([CH2:62][CH3:63])[CH2:59][CH2:60][NH2:61])[CH3:57].CN1[C:69](=[O:70])CCC1>CN1C(=O)CCC1.C(Cl)Cl.CCN(C(C)C)C(C)C.C(Cl)Cl>[CH2:56]([N:58]([CH2:62][CH3:63])[CH2:59][CH2:60][NH:61][C:30]([C:26]1[CH:27]=[C:28]2[C:23](=[CH:24][CH:25]=1)[N:22]=[C:21]([C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[C:20]([C:17]1[CH:18]=[CH:19][C:14]([CH2:13][N:10]3[CH2:9][CH2:8][CH:7]([N:6]4[C:5]5[CH:39]=[CH:40][CH:41]=[CH:42][C:4]=5[NH:3][C:2]4=[O:1])[CH2:12][CH2:11]3)=[CH:15][CH:16]=1)=[N:29]2)=[O:31])[CH3:57].[CH2:56]([N:58]([CH2:62][CH3:63])[CH2:59][CH2:60][NH:61][C:69]([C:25]1[CH:24]=[C:23]2[C:28](=[CH:27][CH:26]=1)[N:29]=[C:20]([C:17]1[CH:18]=[CH:19][C:14]([CH2:13][N:10]3[CH2:9][CH2:8][CH:7]([N:6]4[C:5]5[CH:39]=[CH:40][CH:41]=[CH:42][C:4]=5[NH:3][C:2]4=[O:1])[CH2:12][CH2:11]3)=[CH:15][CH:16]=1)[C:21]([C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)=[N:22]2)=[O:70])[CH3:57]

Participants

9

Reactant 5

HCID 13387N-methyl-2-pyrrolidoneHCID 60993N,N-DiethylethylenediamineHCID 757711-HydroxybenzotriazoleHCID 160435CarbodiimideHCID 10196532HCID 10196532, compound2×

Product 2

HCID 10055074HCID 10055074, compoundHCID 10240275N-[2-(diethylamino)ethyl]-3-[4-[[4-(2-oxo-3H-benzimidazol-1-yl)piperidin-1-yl]methyl]phenyl]-2-phenylquinoxaline-6-carboxamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 131726466HCID 131726466, compoundSolvent

Procedure

The mixture of 3-(4-{[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-2-phenylquinoxaline-6-carboxylic acid (7-1) and 2-(4-{[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-3-phenylquinoxaline-6-carboxylic acid (7-1), 222 mg (0.4 mmol) was dissolved in NMP/DCM/DIEA (10 mL, 9/1). To this solution was added HOBt (152 mg, 1.0 mmol), PS-carbodiimide (1.1 g, 1.3 mmol), and DCM (5 mL). The resultant mixture was shaken 0.5 h. After this time, N,N-diethylethane-1,2-diamine (232 mg, 2.0 mmol) was added to the NMP solution and the reaction was shaken over weekend. After this time, LCMS indicated that the coupling reaction was complete. The resin was filtered and washed with MeOH (3×15 mL). The combined solution was dried to give a brown residue. This residue was then purified on an Agilent 1100 series Mass Guided HPLC purification system to afford the two pure regioisomers N-[2-(diethylamino)ethyl]-3-(4-{[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-2-phenylquinoxaline-6-carboxamide (7-2) (50.7 mg) and N-[2-(diethylamino)ethyl]-2-(4-{[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-3-phenylquinoxaline-6-carboxamide (7-3) (119 mg). Analytical data for N-[2-(diethylamino)ethyl]-3-(4-{[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-2-phenylquinoxaline-6-carboxamide (7-2): Analytical LCMS: single peak (214 nm) at 2.084 min (CH3CN/H2O/1% TFA, 4 min gradient). 1H NMR (500 MHz, DMSO-d6): δ 10.96 (s, 1H), 10.10 (s, 1H), 9.50 (s, 1H), 9.20 (t, J=5.9 Hz, 1H), 8.69 (s, 1H), 8.26–8.34 (m, 2H), 7.49–7.66 (m, 6H), 7.35–7.47 (m, 3H), 7.26–7.32 (m, 1H), 6.97–7.04 (m, 3H), 4.48–4.58 (m, 1H), 4.40 (s, 2H), 3.72 (q, J=6.1 Hz, 2H), 3.50 (d, J=11.7 Hz, 2H), 3.34(q, J=5.4 Hz, 2H), 3.20–3.30 (m, 6H), 2.67 (q, J=14.5 Hz, 2H), 1.96 (d, J=13.0 Hz, 2H), 1.25 (t, J=7.5 Hz, 6H). HRMS, calc'd for C40H44N7O2 (M+H), 654.3551; found 654.3573.

Workup

  1. customAfter this time, LCMS indicated that the coupling reaction
  2. filtrationThe resin was filtered
  3. washwashed with MeOH (3×15 mL)
  4. customThe combined solution was dried
  5. customto give a brown residue
  6. customThis residue was then purified on an Agilent 1100 series Mass Guided HPLC purification system

Sources & evidence

ORD record
ord-a68ec88060a243439dc9ba84c2f9ca97
Source dataset
uspto-grants-2007_05
Patent number
US07223738B2

Reaction notes

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