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 1922829Notes

Reaction equation

HRID 1922829 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10](=[CH:12][C:13]2[N:14]([CH3:29])[C:15]3[C:20]([N:21]=2)=[C:19]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[N:18]=[C:17](Cl)[N:16]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[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].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=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]>[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10](=[CH:12][C:13]2[N:14]([CH3:29])[C:15]3[C:20]([N:21]=2)=[C:19]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[N:18]=[C:17]([N:33]2[C:34]4[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=4[N:36]=[C:32]2[CH2:30][CH3:31])[N:16]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 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 62.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A mixture of 3-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethylene)azetidine-1-carboxylic acid tert-butyl ester (1.4 g, 3.33 mmol), 2-ethylbenzimidazole (584 mg, 3.99 mmol), tris(dibenzylideneacetone)dipalladium (152 mg, 0.17 mmol), XPhos (317 mg, 0.66 mmol) and Cs2CO3 (2.17 g, 6.65 mmol) in dioxane (15 mL) was purged with argon then heated at 120° C. for 16 h in a sealed tube. The reaction mixture was filtered through Celite®, washing with EtOAc, and the filtrate concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 0-100%) affording the title compound as a cream solid (1.1 g, 62%). LCMS (method H): RT 3.20 min [M+H]+ 531.4

Workup

  1. customwas purged with argon
  2. filtrationThe reaction mixture was filtered through Celite®
  3. washwashing with EtOAc
  4. concentrationthe filtrate concentrated in vacuo
  5. customThe resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 0-100%)

Sources & evidence

ORD record
ord-5b7bd74cf4d744ca83b312ed95e8988a
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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