Diisopropylamine → HCID 68872500, compound

HRID 490204Notes

Reaction equation

HRID 490204 reaction equation
Cl[CH2:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][CH:7]=1)=[O:4].C(NC(C)C)(C)C.[N:23]1([C:29]2[N:36]=[CH:35][CH:34]=[CH:33][C:30]=2[C:31]#[N:32])[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1>C1(C)C=CC=CC=1>[C:31]([C:30]1[C:29]([N:23]2[CH2:24][CH2:25][N:26]([CH2:2][C:3]([NH:5][C:6]3[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][CH:7]=3)=[O:4])[CH2:27][CH2:28]2)=[N:36][CH:35]=[CH:34][CH:33]=1)#[N:32]

Participants

5

Reactant 3

HCID 7912DiisopropylamineHCID 27364642-chloro-N-[4-(trifluoromethyl)phenyl]acetamideHCID 27372032-(Piperazin-1-yl)pyridine-3-carbonitrile

Product 1

HCID 68872500HCID 68872500, compoundYield 78.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

2-Chloro-N-(4-trifluoromethylphenyl)acetamide (820 mg, 3.45 mmol, Maybridge) and N,N-diisopropylamine (2.5 mL) in toluene (50 mL) were treated with 2-piperazin-1-ylnicotinonitrile (800 mg, 4.25 mmol, Chess) and heated to 60° 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 (sodium sulfate), filtered, and the filtrate concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (gradient elution with 20% to 40% ethyl acetate:hexanes) to provide 1.05 g (78% yield) of the title compound as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 2.69 (m, 4H), 3.26 (s, 2H), 3.68 (m, 4H), 6.93 (dd, 1H, J=7.5, 4.7 Hz), 7.68 (AA′BB′, 2H, J=8.8 Hz), 7.88 (AA′BB′, 2H, J=8.5 Hz), 8.07 (dd, 1H, J=7.8, 2.0 Hz), 8.42 (dd, 1H, J=4.7, 2.0 Hz), 10.14 (br s, 1H); MS (DCI/NH3) m/e 390 (M+H)+;

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 (sodium sulfate)
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel (gradient elution with 20% to 40% ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-7fc287a885eb4d4bab666d848b7c715b
Source dataset
uspto-grants-2009_05
Patent number
US07528134B2

Reaction notes

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