Lithium Chloride → HCID 86723421, compound

HRID 2201178Notes

Reaction equation

HRID 2201178 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([Sn](CCCC)(CCCC)CCCC)[S:5][CH:6]=1.[CH3:20][N:21]1[C:33](=[O:34])[N:32]([CH3:35])[C:31]2[C:23](=[C:24]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[N:25]3[C:30]=2[C:29](OS(C(F)(F)F)(=O)=O)=[CH:28][CH2:27][CH2:26]3)[C:22]1=[O:50].[Cl-].[Li+]>C1COCC1.CCOC(C)=O.[Cu]I.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:35][N:32]1[C:31]2=[C:30]3[N:25]([C:24]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)=[C:23]2[C:22](=[O:50])[N:21]([CH3:20])[C:33]1=[O:34])[CH2:26][CH2:27][CH:28]=[C:29]3[C:4]1[S:5][CH:6]=[C:2]([CH3:1])[N:3]=1

Participants

8

Reactant 3

HCID 433294Lithium ChlorideHCID 164271304-Methyl-2-(tributylstannyl)-1,3-thiazole6×HCID 86723422HCID 86723422, compound2×

Product 1

HCID 86723421HCID 86723421, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Methyl-2-tributylstannanyl-thiazole (Intermediate J) (491 mg, 1.265 mmol) was added to a suspension of trifluoro-methanesulfonic acid 2,4-dimethyl-1,3-dioxo-9-phenyl-1,2,3,4,7,8-hexahydro-2,4,8a-triaza-fluoren-5-yl ester (Intermediate K) (480 mg, 1.054 mmol), lithium chloride (4.47 mg, 0.105 mmol), copper(I) iodide (20.07 mg, 0.105 mmol) and PdCl2(dppf) (77 mg, 0.105 mmol) in THF (12 ml) and the mixture heated at reflux under nitrogen for 2 h. Further 4-methyl-2-tributylstannanyl-thiazole (Intermediate J) (491 mg, 1.265 mmol) was added and the mixture continued at reflux for 2 h, then further 4-methyl-2-tributylstannanyl-thiazole (Intermediate J) (491 mg, 1.265 mmol) was added and the mixture stirred at reflux for 1 h. The mixture was cooled to RT, diluted with EtOAc and washed with dilute aqueous NH4OH, water and brine. The organic phase was dried over sodium sulphate and evaporated under reduced pressure. The residue was triturated with MeOH/Et2O and the precipitate collected by filtration. The precipitate was purified by chromatography on silica, eluting with 50% EtOAc in hexane. Trituration with Et2O and collection by filtration afforded 1,3-dimethyl-10-(4-methylthiazol-2-yl)-5-phenyl-7,8-dihydropyrimido[4,5-a]indolizine-2,4(1H,3H)-dione as a pale yellow solid

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux under nitrogen for 2 h
  3. temperatureat reflux for 2 h
  4. temperatureat reflux for 1 h
  5. washwashed with dilute aqueous NH4OH, water and brine
  6. dry with materialThe organic phase was dried over sodium sulphate
  7. customevaporated under reduced pressure
  8. customThe residue was triturated with MeOH/Et2O
  9. filtrationthe precipitate collected by filtration
  10. customThe precipitate was purified by chromatography on silica
  11. washeluting with 50% EtOAc in hexane
  12. customTrituration with Et2O and collection
  13. filtrationby filtration

Sources & evidence

ORD record
ord-805e028a33654b34aecde090750cdc40
Source dataset
uspto-grants-2016_06
Patent number
US09359381B2

Reaction notes

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