1,2-Dichloroethane → 6-Chloro-2-(4-(4-methylpiperazine-1-carbonyl)phenylamino)nicotinamide

HRID 2044057Notes

Reaction equation

HRID 2044057 reaction equation
[C:1]([C:4]1[C:5]([NH:11][C:12]2[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[CH:14][CH:13]=2)=[N:6][C:7]([Cl:10])=[CH:8][CH:9]=1)(=[O:3])[NH2:2].[CH3:21][N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C.O>[Cl:10][C:7]1[CH:8]=[CH:9][C:4]([C:1]([NH2:2])=[O:3])=[C:5]([NH:11][C:12]2[CH:13]=[CH:14][C:15]([C:16]([N:25]3[CH2:26][CH2:27][N:22]([CH3:21])[CH2:23][CH2:24]3)=[O:18])=[CH:19][CH:20]=2)[N:6]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 531671-MethylpiperazineHCID 757711-HydroxybenzotriazoleHCID 574896104-(3-Carbamoyl-6-chloropyridin-2-ylamino)benzoic acid

Product 1

HCID 574896116-Chloro-2-(4-(4-methylpiperazine-1-carbonyl)phenylamino)nicotinamideYield 19.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A suspension of 4-(3-carbamoyl-6-chloropyridin-2-ylamino)benzoic acid (700 mg, 2.400 mmol), 1-methylpiperazine (288 mg, 2.88 mmol), HOBT (441 mg, 2.88 mmol), and EDC (552 mg, 2.88 mmol) in DMF (4 mL) was stirred at rt for 2 h. The reaction mixture was diluted with water and the resulting precipitate filtered and purified by MPLC chromatography (ISCO, solid loaded on CELITE®, 10% NH4OH/MeOH/CH2Cl2, 40 g silica gel column) to give 175 mg of 6-chloro-2-(4-(4-methylpiperazine-1-carbonyl)phenylamino)nicotinamide. LCMS: (M+H)+=374.05, 376.07 (Cl pattern); 1H NMR (400 MHz, CDCl3) δ ppm 10.74 (1H, s), 7.64 (3H, dd, J=8.13, 5.49 Hz), 7.21 (2H, d, J=8.79 Hz), 6.67 (1H, d, J=7.91 Hz), 3.38-3.97 (4 H, m), 2.34-2.59 (4H, m), 2.33 (3H, s), 1.70 (2H, s).

Workup

  1. filtrationthe resulting precipitate filtered
  2. custompurified by MPLC chromatography (ISCO, solid loaded on CELITE®, 10% NH4OH/MeOH/CH2Cl2, 40 g silica gel column)

Sources & evidence

ORD record
ord-f35a9a7208c84bc2af5f31c71b53f602
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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