2-Ethylbenzimidazole → HCID 59605258, compound

HRID 1946163Notes

Reaction equation

HRID 1946163 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:15]2[N:16]([CH3:31])[C:17]3[C:22]([N:23]=2)=[C:21]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[N:20]=[C:19](Cl)[N:18]=3)([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:32]([C:34]1[NH:35][C:36]2[CH:42]=[CH:41][CH:40]=[CH:39][C:37]=2[N:38]=1)[CH3:33].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>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[CH2:13][CH2:12][C:11]([C:15]2[N:16]([CH3:31])[C:17]3[C:22]([N:23]=2)=[C:21]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[N:20]=[C:19]([N:35]2[C:36]4[CH:42]=[CH:41][CH:40]=[CH:39][C:37]=4[N:38]=[C:34]2[CH2:32][CH3:33])[N:18]=3)([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 158072-EthylbenzimidazoleHCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl2×HCID 59605333HCID 59605333, compound

Product 1

HCID 59605258HCID 59605258, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)-4-hydroxypiperidine-1-carboxylic acid tert-butyl ester (2.5 g, 5.52 mmol), 2-ethylbenzimidazole (968 mg, 6.62 mmol), tris(dibenzylideneacetone)dipalladium (126 mg, 0.14 mmol), XPhos (263 mg, 0.55 mmol) and K3PO4 (2.34 g, 11.04 mmol) in dioxane (50 mL) was purged with N2 then heated at 100° C. for 6 h before further tris(dibenzylideneacetone)dipalladium (126 mg, 0.14 mmol) and XPhos (263 mg, 0.55 mmol) were added. The resulting mixture was heated at 100° C. for 18 h then diluted with 2-methyl THF and filtered through Celite®. The filtrate was washed with H2O and brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 40-100%) affording 4-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-4-hydroxypiperidine-1-carboxylic acid tert-butyl ester (2.6 g, 84%). LCMS (method H): RT 2.99 min, [M+H]+ 563.4

Workup

  1. customwas purged with N2
  2. additionwere added
  3. filtrationfiltered through Celite®
  4. washThe filtrate was washed with H2O and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 40-100%)

Sources & evidence

ORD record
ord-f456e3fe92a44776aa3848038223db64
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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