2-Methyl-4-(tributylstannyl)pyridine → N-[2,3'-Bipyridin]-6'-yl-2',3-dimethyl[2,4'-bipyridine]-5-acetamide

HRID 592161

Reaction equation

HRID 592161 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:8]=[N:9][C:10]([NH:13][C:14](=[O:24])[CH2:15][C:16]2[CH:17]=[N:18][C:19](Cl)=[C:20]([CH3:22])[CH:21]=2)=[CH:11][CH:12]=1.[CH3:25][C:26]1[CH:31]=[C:30]([Sn](CCCC)(CCCC)CCCC)[CH:29]=[CH:28][N:27]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:8]=[N:9][C:10]([NH:13][C:14](=[O:24])[CH2:15][C:16]2[CH:21]=[C:20]([CH3:22])[C:19]([C:30]3[CH:29]=[CH:28][N:27]=[C:26]([CH3:25])[CH:31]=3)=[N:18][CH:17]=2)=[CH:11][CH:12]=1

Participants

5

Reactant 2

HCID 216605742-Methyl-4-(tributylstannyl)pyridineHCID 58447789N-(2,3'-bipyridin-6'-yl)-2-(6-chloro-5-methylpyridin-3-yl)acetamide

Product 1

HCID 46927131N-[2,3'-Bipyridin]-6'-yl-2',3-dimethyl[2,4'-bipyridine]-5-acetamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
118 °C

Procedure

To a reaction tube were added 5 N-(2,3′-bipyridin-6′-yl)-2-(6-chloro-5-methylpyridin-3-yl)acetamide 124-2 (52 mg, 0.15 mmol), 2-methyl-4-(tributylstannyl)pyridine (115 mg, 0.3 mmol), and Pd(PPh3)4 (35 mg, 0.03 mmol). The tube was subjected to vacuum and back filled with argon. DMF (1.0 ml) was added and the mixture was heated in 118° C. oil bath overnight. After cooled to room temperature, the mixture was filtered through celite, washed and diluted with ethyl acetate (30 ml) and extracted with 0.1 N HCl solution (30 ml). The acidic aqueous phase was treated with Na2CO3 to have pH around 9 and extracted with ethyl acetate (3×20 ml). The combined organic phase was dried over Na2SO4 and concentrated by evaporation. The residue was subjected to silica gel column chromatography with 5% MeOH in DCM as eluent to give N-(2,3′-bipyridin-6′-yl)-2-(2′,3-dimethyl-2,4′-bipyridin-5-yl)acetamide 124 as white solid. MS m/z 396.3 (M+1); 1H NMR 400 MHz (CDCl3) δ 8.93-8.89 (m, 1H), 8.72˜8.67 (m, 1 H), 8.59 (d, 1 H), 8.51 (d, 1 H), 8.37˜8.29 (m, 2 H), 8.23 (bs, 1 H), 7.76(m, 1H), 7.71 (m, 1 H), 7.65 (d, 1 H), 7.33 (bs, 1 H), 7.30˜7.24 (m, 1 H), 3.81 (s, 2H), 2.63 (s, 3H), 2.38 (s, 3 H).

Workup

  1. additionback filled with argon
  2. temperatureAfter cooled to room temperature
  3. filtrationthe mixture was filtered through celite
  4. washwashed
  5. additiondiluted with ethyl acetate (30 ml)
  6. extractionextracted with 0.1 N HCl solution (30 ml)
  7. additionThe acidic aqueous phase was treated with Na2CO3
  8. extractionextracted with ethyl acetate (3×20 ml)
  9. dry with materialThe combined organic phase was dried over Na2SO4
  10. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-825350d946924b4a921c01caf2b48078
Source dataset
uspto-grants-2016_01
Patent number
US09238646B2

Linked notes

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