Cesium carbonate → 2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde

HRID 1945628Notes

Reaction equation

HRID 1945628 reaction equation
CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.Cl[C:36]1[N:44]=[C:43]2[C:39]([N:40]=[C:41]([CH:46]=[O:47])[N:42]2[CH3:45])=[C:38]([N:48]2[CH2:53][CH2:52][O:51][CH2:50][CH2:49]2)[N:37]=1.[CH2:54]([C:56]1[NH:60][C:59]2[CH:61]=[CH:62][CH:63]=[CH:64][C:58]=2[N:57]=1)[CH3:55].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:54]([C:56]1[N:57]([C:36]2[N:44]=[C:43]3[C:39]([N:40]=[C:41]([CH:46]=[O:47])[N:42]3[CH3:45])=[C:38]([N:48]3[CH2:53][CH2:52][O:51][CH2:50][CH2:49]3)[N:37]=2)[C:58]2[CH:64]=[CH:63][CH:62]=[CH:61][C:59]=2[N:60]=1)[CH3:55]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596034722-Chloro-9-methyl-6-morpholino-9H-purine-8-carbaldehyde

Product 1

HCID 596059872-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehydeYield 57.5%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of Pd2(dba)3 (458 mg, 0.5 mmol), Xphos (954 mg, 2.0 mmol), 2-chloro-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (5.64 g, 20.0 mmol), 2-ethyl-1H-benzoimidazole (3.21 g, 22.0 mmol), cesium carbonate (9.78 g, 30.0 mmol) in dioxane (80 mL) was degassed for 5 min and heated at reflux for 18 h. The reaction mixture was filtered through a pad of celite while still hot, and the pad was washed with hot dioxane. The combined filtrate was concentrated under reduced pressure to give a residue which was triturated in Et2O (ca 100 mL), filtered and dried at 50° C. under vacuum to give 2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde as a yellow solid (4.5 g). LCMS (Method H): RT 3.63 min; [M+MeOH]+ 424

Workup

  1. customwas degassed for 5 min
  2. temperatureheated
  3. temperatureat reflux for 18 h
  4. filtrationThe reaction mixture was filtered through a pad of celite while still hot, and the pad
  5. washwas washed with hot dioxane
  6. concentrationThe combined filtrate was concentrated under reduced pressure
  7. customto give a residue which
  8. customwas triturated in Et2O (ca 100 mL)
  9. filtrationfiltered
  10. customdried at 50° C. under vacuum

Sources & evidence

ORD record
ord-631da9cf4b274d8bb57074f66b9a8bdc
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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