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

HRID 1945657Notes

Reaction equation

Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH3:11])=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[N:3]=1.[CH2:18]([C:20]1[NH:21][C:22]2[CH:28]=[CH:27][CH:26]=[CH:25][C:23]=2[N:24]=1)[CH3:19].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]>[CH2:18]([C:20]1[N:21]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[CH:7][N:8]3[CH3:11])=[C:4]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[N:3]=2)[C:22]2[CH:28]=[CH:27][CH:26]=[CH:25][C:23]=2[N:24]=1)[CH3:19]

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 2-chloro-9-methyl-6-morpholin-4-yl-9H-purine (4.0 g, 15.8 mmol), 2-ethylbenzimidazole (2.8 g, 19.0 mmol), tris(dibenzylideneacetone)dipalladium (724 mg, 0.79 mmol), Xphos (1.5 g, 3.16 mmol) and Cs2CO3 (10.3 g, 31.6 mmol) in dioxane (90 mL) was purged with argon then heated at 120° C. for 16 h in a sealed reactor. The reaction mixture was filtered through a pad of celite, washing with EtOAc. The filtrate was concentrated in vacuo and purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-10%) affording 2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine as an orange solid (3.49 g, 96%). LCMS (method H): RT 3.46 min, [M+H]+ 364.5

Workup

customwas purged with argon
filtrationThe reaction mixture was filtered through a pad of celite
washwashing with EtOAc
concentrationThe filtrate was concentrated in vacuo
custompurified by column chromatography (Si—PCC, MeOH:EtOAc, 0-10%)

Sources & evidence

ORD record: ord-96bf07ed01154af28d348b02d5d30f0f
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08394796B2

Reaction notes

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