Ammonia → HCID 11255616, compound

HRID 1372841Notes

Reaction equation

HRID 1372841 reaction equation
I[C:2]1[CH:16]=[CH:15][C:5]([O:6][CH:7]2[CH:12]3[CH2:13][CH2:14][N:9]([CH2:10][CH2:11]3)[CH2:8]2)=[CH:4][CH:3]=1.C([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[NH:25][C:26](=O)[C:27](F)(F)F)#C.C([O-])([O-])=O.[K+].[K+].N>CS(C)=O.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:9]12[CH2:14][CH2:13][CH:12]([CH2:11][CH2:10]1)[CH:7]([O:6][C:5]1[CH:15]=[CH:16][C:2]([C:27]3[C:19]4[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=4)[NH:25][CH:26]=3)=[CH:3][CH:4]=1)[CH2:8]2

Participants

8

Reactant 4

HCID 222AmmoniaHCID 11430Potassium CarbonateHCID 14946833HCID 14946833, compoundHCID 210726043-(4-Iodophenoxy)-1-azabicyclo[2.2.2]octane

Product 1

HCID 11255616HCID 11255616, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

The mixture of the product of Example 1A (330 mg, 1 mmol), N-(2-ethynyl-phenyl)-2,2,2-trifluoro-acetamide (ref. Tetrahedron Lett. 1992, 33, 3915.; 280 mg, 1.3 mmol), Pd2(dba)3 (Aldrich, 19 mg, 0.02 mmol) and K2CO3 (180 mg, 1.3 mmol) in DMSO (3 mL) was stirred at 40° C. under N2 for 2 hours. The reaction was monitored with TLC. After the reaction was complete, it was cooled down to room temperature and diluted with EtOAc (50 mL). It was then washed with brine (3×5 mL). The organic solution was concentrated and the title product was purified by preparative HPLC (Gilson, column, Symmetry® C-8 7 μm, 40×100 mm. Eluting Solvent, MeCN/H2O (with 0.2% v. TFA) (v. 90/10 to 10/90 over 20 min.) Flow rate, 75 mL/min., uv, 250 nm) as solid (113 mg, yield, 36%). 1H NMR (300 MHz, CD3OD) δ 1.43–1.57 (m, 1H), 1.62–1.89 (m, 2H), 2.01–2.15 (m, 1H), 2.16–2.23 (m, 1H), 2.73–3.03 (m, 5H), 3.28–3.40 (m, 1H), 4.51–4.58 (m, 1H), 6.97 (dt, J=8.8, 2.1 Hz, 2H), 7.03–7.17 (m, 2H), 7.36 (s, 1H), 7.37–7.42 (m, 1H), 7.57 (dt, J=8.8, 2.0 Hz, 2H), 7.81 (dt, J=7.8, 1.2 Hz, 1H) ppm. MS (DCl/NH3) m/z 319 (M+H)+.

Workup

  1. temperatureit was cooled down to room temperature
  2. washIt was then washed with brine (3×5 mL)
  3. concentrationThe organic solution was concentrated
  4. customthe title product was purified by preparative HPLC (Gilson, column, Symmetry® C-8 7 μm, 40×100 mm
  5. customEluting Solvent, MeCN/H2O (with 0.2% v. TFA) (v. 90/10 to 10/90 over 20 min.) Flow rate, 75 mL/min., uv, 250 nm) as solid (113 mg, yield, 36%)

Sources & evidence

ORD record
ord-3e71becb153a44f9a01a8581802b0a8f
Source dataset
uspto-grants-2007_01
Patent number
US07160876B2

Reaction notes

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