2-Methyl-4-(tributylstannyl)pyridine → HCID 58447724, compound

HRID 1036304Notes

Reaction equation

HRID 1036304 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:28])[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[C:21](Cl)[CH:20]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH3:29][C:30]1[CH:35]=[C:34]([Sn](CCCC)(CCCC)CCCC)[CH:33]=[CH:32][N:31]=1>CN(C=O)C.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>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:28])[CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[C:21]([C:34]4[CH:33]=[CH:32][N:31]=[C:30]([CH3:29])[CH:35]=4)[CH:20]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

5

Reactant 2

HCID 216605742-Methyl-4-(tributylstannyl)pyridineHCID 67134789HCID 67134789, compound

Product 1

HCID 58447724HCID 58447724, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
118 °C

Procedure

A mixture of N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-chloro-4-cyanophenyl)acetamide as solid 237-3 (17 mg, 0.043 mmol), 2-methyl-4-(tributylstannyl)pyridine (24.5 mg, 0.064 mmol), Pd(PPh3)4 (5 mg, 0.0043 mmol) in DMF (0.6 ml) was stirred at 118° C. under argon overnight. After cooled to room temperature, it was filtered through celite while washed and diluted with ethyl acetate (30 ml). Then it was washed with water (40 ml) and extracted with 0.5 N HCl (30 ml). After the aqueous extraction was treated with Na2CO3 to have the pH adjusted to around 9, the aqueous phase was extracted with ethyl acetate (30 ml×2). The combined organic phases were dried over Na2SO4, concentrated by rotary evaporation and the residue subjected to silica gel column chromatography with MeOH in ethyl acetate (0 to 5%) as eluent to give N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(4-cyano-3-(2-methylpyridin-4-yl)phenyl)acetamide as solid 237. MS m/z 455.2 (M+1); 1H NMR 400 MHz (CDCl3) δ 8.62 (d, 1H), 8.08 (d, 1H), 8.02 (bs, 1H), 7.91 (d, 1H), 7.79 (d, 1H), 7.53-7.47 (m, 2H), 7.34 (bs, 1H), 7.31-7.26 (m, 2H), 3.82 (s, 2H), 3.80-3.75 (m, 2H), 3.65-3.60 (m, 2H), 3.16-3.08 (m, 4H), 2.64 (s, 3H), 2.14 (s, 3H).

Workup

  1. temperatureAfter cooled to room temperature
  2. filtrationit was filtered through celite
  3. washwhile washed
  4. additiondiluted with ethyl acetate (30 ml)
  5. washThen it was washed with water (40 ml)
  6. extractionextracted with 0.5 N HCl (30 ml)
  7. extractionAfter the aqueous extraction
  8. additionwas treated with Na2CO3
  9. extractionthe aqueous phase was extracted with ethyl acetate (30 ml×2)
  10. dry with materialThe combined organic phases were dried over Na2SO4
  11. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-1b54858566df4686bc881c1d394e663f
Source dataset
uspto-grants-2013_10
Patent number
US08546396B2

Reaction notes

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