N,N-Diethyl-p-phenylenediamine → 6-Chloro-2-(4-(diethylamino)phenylamino)nicotinamide

HRID 2044051Notes

Reaction equation

HRID 2044051 reaction equation
Cl[C:2]1[N:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[CH2:12]([N:14]([CH2:22][CH3:23])[C:15]1[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=1)[CH3:13].C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Cl:11][C:9]1[CH:8]=[CH:7][C:3]([C:4]([NH2:6])=[O:5])=[C:2]([NH:21][C:18]2[CH:17]=[CH:16][C:15]([N:14]([CH2:22][CH3:23])[CH2:12][CH3:13])=[CH:20][CH:19]=2)[N:10]=1

Participants

5

Reactant 3

HCID 7120N,N-Diethyl-p-phenylenediamineHCID 2733832Lithium HexamethyldisilazideHCID 221427782,6-Dichloropyridine-3-carboxamide

Product 1

HCID 574896066-Chloro-2-(4-(diethylamino)phenylamino)nicotinamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 2,6-dichloronicotinamide (1 g, 5.24 mmol) and N1,N1-diethylbenzene-1,4-diamine (2.150 g, 13.09 mmol) in THF (50 mL) was added lithium bis(trimethylsilyl)amide (26.2 mL, 26.2 mmol) drop-wise at first then portion-wise at −78° C. The reaction mixture was stirred at rt for 30 min. The ice bath was removed and the reaction mixture was stirred at rt overnight. The reaction mixture was diluted with water, extracted twice with ethyl acetate, and the combined organic layers were washed with water and concentrated. The residue was purified by MPLC (ISCO, hexane/ethyl acetate, 120 g silica gel column) to give 6-chloro-2-(4-(diethylamino)phenylamino)nicotinamide. LCMS: (M+H)+=319.10. 1H NMR (400 MHz, CDCl3) δ ppm 10.44 (1H, s), 7.56 (1H, d, J=7.91 Hz), 7.47 (2H, d, J=9.23 Hz), 6.69 (2H, d, J=9.23 Hz), 6.55 (1H, d, J=7.91 Hz), 5.73 (2H, br. s.), 3.33 (4H, q, J=7.03 Hz), 1.15 (6H, t, J=7.03 Hz).

Workup

  1. customThe ice bath was removed
  2. stirringthe reaction mixture was stirred at rt overnight
  3. additionThe reaction mixture was diluted with water
  4. extractionextracted twice with ethyl acetate
  5. washthe combined organic layers were washed with water
  6. concentrationconcentrated
  7. customThe residue was purified by MPLC (ISCO, hexane/ethyl acetate, 120 g silica gel column)

Sources & evidence

ORD record
ord-fbc30126b70848e8a0f89a6612da8dc8
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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