1,2-Dichloroethane → N-[(5,6-dimethoxypyridin-2-yl)methyl]-6-(2-fluorophenyl)-5'-methyl-3,3'-bipyridine-5-carboxamide

HRID 1675941Notes

Reaction equation

HRID 1675941 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[N:14]=[CH:13][C:12]([C:15]2[CH:16]=[N:17][CH:18]=[C:19]([CH3:21])[CH:20]=2)=[CH:11][C:10]=1[C:22]([OH:24])=O.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH3:39][O:40][C:41]1[CH:42]=[CH:43][C:44]([CH2:49][NH2:50])=[N:45][C:46]=1[O:47][CH3:48].CN1CCOCC1>CN(C)C=O>[CH3:39][O:40][C:41]1[CH:42]=[CH:43][C:44]([CH2:49][NH:50][C:22]([C:10]2[CH:11]=[C:12]([C:15]3[CH:16]=[N:17][CH:18]=[C:19]([CH3:21])[CH:20]=3)[CH:13]=[N:14][C:9]=2[C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[F:2])=[O:24])=[N:45][C:46]=1[O:47][CH3:48]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 574847121-(5,6-Dimethoxypyridin-2-yl)methanamineHCID 673436516-(2-Fluorophenyl)-5'-methyl-3,3'-bipyridine-5-carboxylic acid hydrochloride

Product 1

HCID 25225520N-[(5,6-dimethoxypyridin-2-yl)methyl]-6-(2-fluorophenyl)-5'-methyl-3,3'-bipyridine-5-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-(2-fluorophenyl)-5′-methyl-3,3′-bipyridine-5-carboxylic acid hydrochloride (3-4, 3.0 g, 8.70 mmol) in dimethylformamide (43 mL) cooled to 0° C., was added EDC (2.67 g, 13.92 mmol) and HOBt (2.13 g, 13.92 mmol) followed by 1-(5,6-dimethoxypyridin-2-yl)methanamine (11-6, 1.90 g, 11.31 mmol) and N-methylmorpholine (5.74 mL, 52.2 mmol). The reaction was allowed to warm to room temperature and stir overnight. The reaction mixture was partitioned between ethyl acetate and saturated sodium bicarbonate. The organics were washed with water and brine, then stripped to dryness. The crude product was taken up in DMF/DMSO (30 mL, 1:1), filtered and purified via reverse phase chromatography (5→65% acetonitrile in water with 0.1% TFA buffer). The clean fractions were pooled, partitioned between ethyl acetate and 2M sodium carbonate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated to afford the title compound (3-5) as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.99 (d, J=2.5 Hz, 1H), 8.74 (d, J=2 Hz, 1H) 8.53 (s, 1H), 8.34 (d, J=2.5 Hz, 1H), 7.77 (s, 1H), 7.66 (m, 1H), 7.31 (m, 1H), 7.21 (t, J=14.6 Hz, 1H), 6.98 (d, J=7.8 Hz, 1H), 6.92 (t, J=18.3 Hz, 1H), 6.73 (d, J=7.8 Hz, 1H), 6.46 (m, 1H), 4.44 (d, J=5 Hz, 2H), 3.87 (s, 3H), 3.81(s, 3H), 2.45 (s, 3H). HRMS [M+H] C26H23FN4O3 calc'd 459.1827, found 459.1830.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and saturated sodium bicarbonate
  2. washThe organics were washed with water and brine
  3. filtrationfiltered
  4. custompurified via reverse phase chromatography (5→65% acetonitrile in water with 0.1% TFA buffer)
  5. custompartitioned between ethyl acetate and 2M sodium carbonate
  6. washThe organic layer was washed with water and brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-fc43f89064574f9db6609963df1beb1b
Source dataset
uspto-grants-2011_08
Patent number
US08003797B2

Reaction notes

Loading…