Cesium carbonate → 3-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethylene]azetidine-1-carboxylic acid tert-butyl ester

HRID 1946047Notes

Reaction equation

HRID 1946047 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH:12]=[C:13]3[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14]3)[N:8]2[CH3:11])=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[N:3]=1.[CH2:30]([C:32]1[NH:33][C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1)[CH3:31].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.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].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[CH3:11][N:8]1[C:7]([CH:12]=[C:13]2[CH2:14][N:15]([C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[CH2:16]2)=[N:6][C:5]2[C:9]1=[N:10][C:2]([N:33]1[C:34]3[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=3[N:36]=[C:32]1[CH2:30][CH3:31])=[N:3][C:4]=2[N:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 59605709tert-butyl 3-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methylene)azetidine-1-carboxylate

Product 1

HCID 596052023-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethylene]azetidine-1-carboxylic acid tert-butyl esterYield 82.5%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of tert-butyl 3-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methylene)azetidine-1-carboxylate (0.88 g, 2.9 mmol), 2-ethylbenzimidazole (0.40 g, 2.74 mmol), Xphos (0.10 g, 0.21 mmol), Pd2(dba)3 (0.10 g, 0.11 mmol) and cesium carbonate (1.4 g, 4.2 mmol) in DMF (4.0 mL) was heated in a Biotage microwave at 140° C. for 30 minutes. The reaction mixture was then filtered through paper and then partitioned between brine and EtOAc. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography (0-10% MeOH in DCM) to give the title compound (1.2 g, quant.). LCMS m/z: 531.2 (MH+).

Workup

  1. filtrationThe reaction mixture was then filtered through paper
  2. custompartitioned between brine and EtOAc
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography (0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-40c860cdbb514fc0beb4dce7d0bb3f99
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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