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

HRID 1945627Notes

Reaction equation

HRID 1945627 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)C.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]>[CH3:45][N:42]1[C:41]([CH:46]=[O:47])=[N:40][C:39]2[C:43]1=[N:44][C:36]([N:57]1[C:58]3[CH:64]=[CH:63][CH:62]=[CH:61][C:59]=3[N:60]=[C:56]1[CH3:54])=[N:37][C:38]=2[N:48]1[CH2:53][CH2:52][O:51][CH2:50][CH2:49]1

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 596054202-(2-methylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehydeYield 50%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
145 °C

Procedure

A mixture of Pd2(dba)3 (161 mg, 0.18 mmol), Xphos (CAS Reg. No. 564483-18-7, 336 mg, 0.72 mmol), 2-chloro-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (1.0 g, 3.52 mmol), 2-ethyl-1H-benzoimidazole (500 mg, 3.73 mmol), cesium carbonate (2.3 g, 7 mmol) in dioxane (15 mL) was degassed for 5 min and heated at 145° C. for 30 min under microwave irradiation. The reaction mixture was filtered while still hot through a pad of celite, and the pad was washed with hot dioxane. The product precipitated immediately as a pale yellow solid. The solid was filtered and dried at 50° C. under vacuum to give 9-Methyl-2-(2-methylbenzoimidazol-1-yl)-6-morpholin-4-yl-9H-purine-8-carbaldehyde (650 mg, 50%). Additional material could be recovered from the mother liquors. LCMS (Method H): RT 3.39 min; [M+MeOH]+ 410

Workup

  1. filtrationThe reaction mixture was filtered while still hot through a pad of celite
  2. washthe pad was washed with hot dioxane
  3. customThe product precipitated immediately as a pale yellow solid
  4. filtrationThe solid was filtered
  5. customdried at 50° C. under vacuum

Sources & evidence

ORD record
ord-373b0724f7434aa596ff5a640cc909e1
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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