Sodium Carbonate → N-[(1R)-1-(3,3'-bipyridin-6-yl)ethyl]-2-(4-isopropylphenyl)acetamide

HRID 2383519Notes

Reaction equation

HRID 2383519 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C@H:8]([NH:10][C:11](=[O:22])[CH2:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]([CH3:21])[CH3:20])=[CH:15][CH:14]=2)[CH3:9])=[N:6][CH:7]=1.C(=O)([O-])[O-].[Na+].[Na+].[N:29]1[CH:34]=[CH:33][CH:32]=[C:31](B(O)O)[CH:30]=1>COCCOC.O.[Pd]>[N:6]1[C:5]([C@H:8]([NH:10][C:11](=[O:22])[CH2:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]([CH3:21])[CH3:20])=[CH:15][CH:14]=2)[CH3:9])=[CH:4][CH:3]=[C:2]([C:31]2[CH:30]=[N:29][CH:34]=[CH:33][CH:32]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 24765575N-[(1R)-1-(5-bromopyridin-2-yl)ethyl]-2-(4-isopropylphenyl)acetamide

Product 1

HCID 57948498N-[(1R)-1-(3,3'-bipyridin-6-yl)ethyl]-2-(4-isopropylphenyl)acetamide

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of N-[(1R)-1-(5-bromopyridin-2-yl)ethyl]-2-(4-isopropylphenyl)acetamide (40 mg, 0.11 mmol), tetrakis(triphenyl)phosphine)palladium (0) (1.3 mg, 0.01 mmol), sodium carbonate (22 mg, 0.20 mmol) in DME/water (4:1, 3.0 ml) was added 3-pyridyl boronic acid (19 mg, 0.16 mmol). The reaction was heated for ten minutes in the Smith Personal microwave system at 100° C. and then washed with brine. Organics were extracted with EtOAc and dried over Na2SO4, filtered and concentrated in vacuo to give a red oily solid. Reverse phase prep HPLC chromatography afforded the mono-trifluoroacetate salt of N-[(1R)-1-(3,3′-bipyridin-6-yl)ethyl]-2-(4-isopropylphenyl)acetamide as an oil. 1H NMR (CD3OD, 400 MHz) δ 9.18 (s, 1H); 8.95 (s, 1H); 8.84 (d, J=4.80 Hz, 1H); 8.78 (dd, J=1.20 Hz and 6.40 Hz, 1H); 8.29 (dd, J=2.40 and 8.40 Hz, 1H); 8.06 (dd, J=5.20 and 8.20 Hz, 1H); 7.61 (d, J=8.40 Hz, 1H); 7.19 (m, 4H); 5.10 (q, J=6.80 Hz, 1H); 3.55 (s, 2H); 2.86 (m, 1H); 1.55 (d, J=7.20 Hz, 3H); 1.21 (d, J=6.80 Hz, 6H); HRMS (ES) exact mass calcd for C23, H25, N3O: 360.2071, Found: 360.2070.

Workup

  1. washwashed with brine
  2. extractionOrganics were extracted with EtOAc
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a red oily solid

Sources & evidence

ORD record
ord-27660676aa2045c7aeb72fffd11aeba4
Source dataset
uspto-grants-2012_09
Patent number
US08263627B2

Reaction notes

Loading…