Diisopropylethylamine → Benzamide, 5-chloro-N-[(1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-2-methyl-3-[(4-oxocyclohexyl)thio]-

HRID 2208936Notes

Reaction equation

HRID 2208936 reaction equation
Br[C:2]1[C:3]([CH3:22])=[C:4]([CH:18]=[C:19]([Cl:21])[CH:20]=1)[C:5]([NH:7][CH2:8][C:9]1[C:10](=[O:17])[NH:11][C:12]([CH3:16])=[CH:13][C:14]=1[CH3:15])=[O:6].[SH:23][CH:24]1[CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]1.CCN(C(C)C)C(C)C>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[Cl:21][C:19]1[CH:20]=[C:2]([S:23][CH:24]2[CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]2)[C:3]([CH3:22])=[C:4]([CH:18]=1)[C:5]([NH:7][CH2:8][C:9]1[C:10](=[O:17])[NH:11][C:12]([CH3:16])=[CH:13][C:14]=1[CH3:15])=[O:6]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 15349296HCID 15349296, compoundHCID 70873688Benzamide, 3-bromo-5-chloro-N-[(1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-2-methyl-

Product 1

HCID 70874028Benzamide, 5-chloro-N-[(1,2-dihydro-4,6-dimethyl-2-oxo-3-pyridinyl)methyl]-2-methyl-3-[(4-oxocyclohexyl)thio]-Yield 126.9%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 3-bromo-5-chloro-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)-methyl)-2-methylbenzamide (0.35 g, 0.91 mmol.), 4-mercaptocyclohexanone (0.142 g, 1.09 mmol) and DIPEA (0.235 g, 1.82 mmol) in dioxane was purged with argon for 10 min. Then, Pd(OAc)2 (0.01 g, 0.044 mmol) and Xantphos (0.052 g, 0.089 mmol) were added and argon was purged again for 10 min. The reaction mixture was stirred at 100° C. overnight. After completion of the reaction, water was added and extraction was carried out using ethyl acetate. The combined organic layers were washed with water, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford crude material which was purified by column chromatography to afford the title compound (0.50 g, 88%).

Workup

  1. customargon was purged again for 10 min
  2. customAfter completion of the reaction, water
  3. additionwas added
  4. extractionextraction
  5. washThe combined organic layers were washed with water
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto afford crude material which
  10. customwas purified by column chromatography

Sources & evidence

ORD record
ord-02c7a5ee341847e18995cb33a0273157
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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