Dabco → HCID 10798028, compound

HRID 2176176Notes

Reaction equation

HRID 2176176 reaction equation
I[C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].Cl.[N:10]12[CH2:17][CH2:16][CH:13]([CH2:14][CH2:15]1)[C:12](=O)[CH2:11]2.N12CCN(CC1)CC2.S([O-])([O-])(=O)=O.[Mg+2]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:10]12[CH2:17][CH2:16][CH:13]([C:12]3[NH:4][C:3]4[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=4[C:11]=31)[CH2:14][CH2:15]2

Participants

7

Reactant 4

HCID 9237DabcoHCID 119952-IodoanilineHCID 24083Sulfuric acid magnesium salt (1:1)HCID 1020191-Azabicyclo(2.2.2)octan-3-one, hydrochloride (1:1)

Product 1

HCID 10798028HCID 10798028, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2-iodoaniline (1.00 g, 4.57 mmol; Aldrich), quinuclidin-3-one hydrochloride (1.24 g, 7.67 mmol; Aldrich), palladium(II) acetate (51 mg, 0.23 mmol; Aldrich), 1,4-diazabicyclo[2.2.2]octane (DABCO; 1.79 g, 15.98 mmol; Aldrich) and magnesium sulfate (0.88 g, 7.31 mmol; Aldrich) in dry N,N-dimethylformamide (14 mL) was evacuated and purged with nitrogen (three cycles) and stirred at 110° C. for 18 hours. The reaction mixture was cooled to ambient temperature and filtered through a microfiber frit. The filtrate was concentrated in vacuo, dissolved in methanol (10 mL) and purified by preparative HPLC [Waters XBridge RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 10-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford the title compound: 1H NMR (500 MHz, methanol-d4) δ ppm 1.52-1.66 (m, 2H), 1.97-2.06 (m, 2H), 2.58-2.71 (m, 2H), 3.24-3.31 (m, 2H), 3.40-3.45 (quintet, J=2.9 Hz, 1H), 6.94-7.05 (m, 2H), 7.31-7.35 (m, 1H), 7.52-7.57 (m, 1H); MS (APCI) m/z 199 (M+H)+.

Workup

  1. customwas evacuated
  2. custompurged with nitrogen (three cycles)
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. filtrationfiltered through a microfiber frit
  5. concentrationThe filtrate was concentrated in vacuo
  6. dissolutiondissolved in methanol (10 mL)
  7. custompurified by preparative HPLC [Waters XBridge RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 10-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]

Sources & evidence

ORD record
ord-93d33027ed8a4240805ab09cf5aa15cc
Source dataset
uspto-grants-2015_06
Patent number
US09063126B2

Reaction notes

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