1,2-Dichloroethane → N-[(5,6-dimethoxy-2-pyridinyl)methyl]-2-(3-fluorophenyl)-5-(5-methyl-3-pyridinyl)pyridine-3-carboxamide

HRID 1675942Notes

Reaction equation

HRID 1675942 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([C:9]2[N:14]=[CH:13][C:12]([C:15]3[CH:16]=[N:17][CH:18]=[C:19]([CH3:21])[CH:20]=3)=[CH:11][C:10]=2[C:22](O)=[O:23])[CH:6]=[CH:7][CH:8]=1.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:5]2[CH:6]=[CH:7][CH:8]=[C:3]([F:2])[CH:4]=2)=[O:23])=[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 673474386-(3-Fluorophenyl)-5'-methyl-3,3'-bipyridine-5-carboxylic acid hydrochloride

Product 1

HCID 25225521N-[(5,6-dimethoxy-2-pyridinyl)methyl]-2-(3-fluorophenyl)-5-(5-methyl-3-pyridinyl)pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 6-(3-fluorophenyl)-5′-methyl-3,3′-bipyridine-5-carboxylic acid hydrochloride (3-6, prepared by the method described above for the preparation of 3-4, 2.5 g, 7.25 mmol) in dimethylformamide (36 mL) cooled to 0° C., was added EDC (1.95 g, 10.2 mmol) and HOBt (1.67 g, 10.9 mmol) followed by 1-(5,6-dimethoxypyridin-2-yl)methanamine (11-6, 1.46 g, 8.7 mmol) and N-methylmorpholine (4.78 mL, 43.5 mmol). The reaction stirred for 15 minutes and then was allowed to warm to room temperature. After 3.5 hours the reaction mixture was partitioned between ethyl acetate and saturated sodium bicarbonate. The organics were washed with water and brine, dried over Na2SO4/MgSO4, filtered and stripped to dryness. The crude product was recrystallized from chloroform/ethyl ether to afford the title compound (3-7) as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.96 (d, J=2.2 Hz, 1H), 8.72 (d, J=1.7 Hz, 1H), 8.56 (s, 1H), 8.23 (d, J=2.2 Hz, 1H), 7.76 (s, 1H), 7.44 (d, J=7.8 Hz, 1H), 7.40 (d, J=9.5 Hz, 1H), 7.24 (m, 1H), 6.99 (m, 2H), 6.74 (d, J=7.8 Hz, 1H), 6.33 (m, 1H), 4.44 (d, J=5.4 Hz, 2H), 3.88 (s, 3H), 3.76(s, 3H), 2.45 (s, 3H). HRMS [M+H] C26H23FN4O3 calc'd 459.1827, found 459.1832.

Workup

  1. temperatureto warm to room temperature
  2. customAfter 3.5 hours the reaction mixture was partitioned between ethyl acetate and saturated sodium bicarbonate
  3. washThe organics were washed with water and brine
  4. dry with materialdried over Na2SO4/MgSO4
  5. filtrationfiltered
  6. customThe crude product was recrystallized from chloroform/ethyl ether

Sources & evidence

ORD record
ord-664836915f4244e2a70a2bc5207a80b1
Source dataset
uspto-grants-2011_08
Patent number
US08003797B2

Reaction notes

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