1,4-Dioxane → 7-(2-chloro-5-fluoro-phenyl)-6-cyano-4-oxo-5-pyridin-4-yl-4,5-dihydro-3H-1-thia-3,5,8-triaza-acenaphthylene-2-carboxylic acid ethyl ester

HRID 32342Notes

Reaction equation

HRID 32342 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[S:7][C:8]2[N:9]=[C:10](Cl)[C:11]([C:25]#[N:26])=[C:12]3[C:17]=2[C:16]=1[NH:15][C:14](=[O:18])[N:13]3[C:19]1[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=1)=[O:5])[CH3:2].[Cl:28][C:29]1[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:30]=1B(O)O.O1CCOCC1>C([O-])(O)=O.[Na+].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>[CH2:1]([O:3][C:4]([C:6]1[S:7][C:8]2[N:9]=[C:10]([C:34]3[CH:33]=[C:32]([F:35])[CH:31]=[CH:30][C:29]=3[Cl:28])[C:11]([C:25]#[N:26])=[C:12]3[C:17]=2[C:16]=1[NH:15][C:14](=[O:18])[N:13]3[C:19]1[CH:20]=[CH:21][N:22]=[CH:23][CH:24]=1)=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 312751,4-DioxaneHCID 226481162-Chloro-5-fluorobenzeneboronic acidHCID 597943237-chloro-6-cyano-4-oxo-5-pyridin-4-yl-4,5-dihydro-3H-1-thia-3,5,8-triaza-acenaphthylene-2-carboxylic acid ethyl ester

Product 1

HCID 597943217-(2-chloro-5-fluoro-phenyl)-6-cyano-4-oxo-5-pyridin-4-yl-4,5-dihydro-3H-1-thia-3,5,8-triaza-acenaphthylene-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 516892Sodium BicarbonateSolvent2×

Procedure

7-chloro-6-cyano-4-oxo-5-pyridin-4-yl-4,5-dihydro-3H-1-thia-3,5,8-triaza-acenaphthylene-2-carboxylic acid ethyl ester Compound 3a (537 mg, 1.35 mmol), prepared using the procedure of Example 1, was combined with 2-chloro-5-fluorophenyl-boronic acid (468 mg, 2.69 mmol), Pd(Ph3P)4 (156 mg, 0.135 mmol), sat'd NaHCO3 (15 mL) and 1,4-dioxane (40 mL). The reaction mixture was refluxed for 2 hrs then diluted with sat'd NaHCO3 and extracted with EtOAc. The organic layer was dried (MgSO4) and evaporated. The solid was recrystallized from EtOAc to give 7-(2-chloro-5-fluoro-phenyl)-6-cyano-4-oxo-5-pyridin-4-yl-4,5-dihydro-3H-1-thia-3,5,8-triaza-acenaphthylene-2-carboxylic acid ethyl ester Compound 15 (440 mg) as a pale yellow solid. LC/MS 494, 496 (MH+).

Workup

  1. temperatureThe reaction mixture was refluxed for 2 hrs
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layer was dried (MgSO4)
  4. customevaporated
  5. customThe solid was recrystallized from EtOAc

Sources & evidence

ORD record
ord-72780db29f8b4a80ba648d4899e978d5
Source dataset
uspto-grants-2008_09
Patent number
US07427625B2

Reaction notes

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