Cesium carbonate → HCID 59605310, compound

HRID 1946152Notes

Reaction equation

HRID 1946152 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][CH2:13][N:14]([CH3:23])[C:15]3([CH3:22])[CH2:19][CH2:18][S:17](=[O:21])(=[O:20])[CH2:16]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].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]>[CH2:30]([C:32]1[N:33]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[C:7]([CH2:12][CH2:13][N:14]([CH3:23])[C:15]4([CH3:22])[CH2:19][CH2:18][S:17](=[O:20])(=[O:21])[CH2:16]4)[N:8]3[CH3:11])=[C:4]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[N:3]=2)[C:34]2[CH:40]=[CH:39][CH:38]=[CH:37][C:35]=2[N:36]=1)[CH3:31]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 59606078HCID 59606078, compound

Product 1

HCID 59605310HCID 59605310, compoundYield 55%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

A mixture of [2-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)ethyl]methyl-(3-methyl-1,1-dioxotetrahydrothiophen-3-yl)amine (87 mg, 0.20 mmol), 2-ethylbenzimidazole (32 mg, 0.22 mmol), tris(dibenzylideneacetone)dipalladium (5 mg, 2.5 mol %), XPhos (9 mg, 10 mol %) and Cs2CO3 (96 mg, 0.30 mmol) in dioxane (2 mL) was purged with argon then heated at 110° C. for 20 h in a sealed tube. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH/DCM. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-5%) affording 748 as an off-white solid (60 mg, 55%). LCMS (method I): RT 2.63 min, [M+H]+ 553.1. 1H NMR (CDCl3, 400 MHz): δ 8.01-7.98 (1 H, m), 7.75-7.74 (1 H, m), 7.30-7.23 (2 H, m), 4.34 (4 H, brd s), 3.87 (4 H, t, J=4.78 Hz), 3.78 (3 H, s), 3.37-3.30 (3 H, m), 3.01-3.00 (7 H, m), 2.40-2.30 (4 H, m), 2.08-2.08 (1 H, m), 1.44 (3 H, t, J=7.48 Hz), 1.29 (3 H, s)

Workup

  1. customwas purged with argon
  2. washwas washed with MeOH
  3. washthe product eluted with 2M NH3/MeOH/DCM
  4. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-5%)

Sources & evidence

ORD record
ord-87b2f8c781784067a89526e3d61a5fd0
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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