Sodium Carbonate → HCID 86643696, compound

HRID 1672759Notes

Reaction equation

HRID 1672759 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:8]2[CH2:17][C@H:16]3[N:12]([CH2:13][CH2:14][CH2:15]3)[C:11]3[N:18]=[C:19]([S:22][CH3:23])[N:20]=[CH:21][C:10]=3[C:9]2=[O:24])[CH:5]=[CH:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[Cl:48][C:49]1[CH:54]=[C:53](I)[CH:52]=[CH:51][N:50]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[Cl:48][C:49]1[CH:54]=[C:53]([C:2]2[CH:3]=[C:4]([N:8]3[CH2:17][CH:16]4[N:12]([CH2:13][CH2:14][CH2:15]4)[C:11]4[N:18]=[C:19]([S:22][CH3:23])[N:20]=[CH:21][C:10]=4[C:9]3=[O:24])[CH:5]=[CH:6][CH:7]=2)[CH:52]=[CH:51][N:50]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 15165112-Chloro-4-iodopyridineHCID 2733548Bis(pinacolato)diboraneHCID 67349728HCID 67349728, compound

Product 1

HCID 86643696HCID 86643696, compoundYield 43.1%

Reagents, catalysts & solvents 2

HCID 178477754HCID 178477754, compoundCatalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

(S)-5-(3-Bromophenyl)-9-methylthio-1,2,3,3a,4,5-hexahydro-5,8,10,10b-tetraazabenzo[e]azulen-6-one (243 mg, 0.599 mmol) obtained in Step 1 of Example 13 was dissolved in 1,4-dioxane (7 mL), and the mixture was stirred at 100° C. for hours after adding bis(pinacolato)diboron (0.380 g, 1.50 mol), [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl2(dppf); 98.0 mg, 0.120 mmol), and potassium acetate (0.295 g, 3.00 mmol). The reaction mixture was filtered through sellite, and the filtrate was diluted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The residue obtained upon concentration under reduced pressure was then purified by silica gel column chromatography. The resulting crude product was dissolved in 1,4-dioxane/water=4/1 (12.5 mL), and the mixture was stirred at 100° C. for 3 hours after adding 2-chloro-4-iodopyridine (216 mg, 0.902 mmol), [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl2(dppf); 49.0 mg, 0.060 mmol), and sodium carbonate (191 mg, 1.80 mmol). The reaction mixture was then filtered through sellite, and the filtrate was extracted with ethyl acetate. The organic layer was then washed with saturated brine, and dried over anhydrous magnesium sulfate. The residue obtained upon concentration under reduced pressure was purified by silica gel column chromatography to give 5-[3-(2-chloropyridin-4-yl)phenyl]-9-methylthio-1,2,3,3a,4,5-hexahydro5,8,10,10b-tetraazabenzo[e]azulen-6-one (113 mg, 43% (2 steps)).

Workup

  1. filtrationThe reaction mixture was filtered through sellite
  2. additionthe filtrate was diluted with ethyl acetate
  3. washThe organic layer was washed with water and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe residue obtained upon concentration under reduced pressure
  6. customwas then purified by silica gel column chromatography
  7. dissolutionThe resulting crude product was dissolved in 1,4-dioxane/water=4/1 (12.5 mL)
  8. stirringthe mixture was stirred at 100° C. for 3 hours
  9. filtrationThe reaction mixture was then filtered through sellite
  10. extractionthe filtrate was extracted with ethyl acetate
  11. washThe organic layer was then washed with saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customThe residue obtained upon concentration under reduced pressure
  14. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-598b95ab8ad54ef0bdb2f7acd70e7619
Source dataset
uspto-grants-2011_08
Patent number
US07998954B2

Reaction notes

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