Diisopropylethylamine → 2-[4-(3-cyano-2-pyridinyl)-1-piperazinyl]-N-(3-nitrophenyl)acetamide

HRID 490160Notes

Reaction equation

HRID 490160 reaction equation
[N:1]1([C:7]2[C:12]([C:13]#[N:14])=[CH:11][CH:10]=[CH:9][N:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.Cl[CH2:25][C:26]([NH:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([N+:35]([O-:37])=[O:36])[CH:30]=1)=[O:27]>C1(C)C=CC=CC=1>[C:13]([C:12]1[C:7]([N:1]2[CH2:2][CH2:3][N:4]([CH2:25][C:26]([NH:28][C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([N+:35]([O-:37])=[O:36])[CH:30]=3)=[O:27])[CH2:5][CH2:6]2)=[N:8][CH:9]=[CH:10][CH:11]=1)#[N:14]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5320662-chloro-N-(3-nitrophenyl)acetamideHCID 27372032-(Piperazin-1-yl)pyridine-3-carbonitrile

Product 1

HCID 104065762-[4-(3-cyano-2-pyridinyl)-1-piperazinyl]-N-(3-nitrophenyl)acetamideYield 25%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

2-(1-Piperazinyl)-3-pyridinecarbonitrile (640 mg, 3.40 mmol) and N,N-diisopropylethylamine (1.0 mL) in toluene (15 mL) at room temperature were treated with N-chloroacetyl-3-nitroaniline (Lancaster, 610 mg, 2.84 mmol) and the reaction was heated at 90° C. for 18 hours. The mixture was allowed to cool to room temperature, transferred to a separatory funnel and washed with saturated aqueous sodium bicarbonate. The organic phase was dried (Na2SO4), filtered, and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (elution with 85% hexanes:ethyl acetate) to provide 256 mg (25% yield) of the title compound as a light tan solid. mp 143-145° C.; 1H NMR (300 MHz, DMSO-d6) δ 2.69 (m, 4H), 3.27 (s, 2H), 3.70 (m, 4H), 6.93 (dd, 1H, J=7.4, 5.0 Hz), 7.61 (dd, 1H, J=8.1, 8.1 Hz), 7.93 (br d, 1H, J=8.2 Hz), 8.06 (dd, 2H, J=7.8, 7.8 Hz), 8.42 (m, 1H), 8.70 (br s, 1H), 10.28 (br s, 1H); MS (DCI/NH3) m/e 367 (M+H)+; Anal. calcd for C18H18N6O3: C, 59.01; H, 4.95; N, 22.94. Found: C, 59.31; H, 5.25; N, 22.66.

Workup

  1. temperatureto cool to room temperature
  2. customtransferred to a separatory funnel
  3. washwashed with saturated aqueous sodium bicarbonate
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under reduced pressure
  7. customThe residue was purified by flash chromatography on silica gel (elution with 85% hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-cf62e6aef6b5469983396800bfc7cf32
Source dataset
uspto-grants-2009_05
Patent number
US07528134B2

Reaction notes

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