Cesium carbonate → HCID 59606084, compound

HRID 1923218Notes

Reaction equation

HRID 1923218 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][CH2:13][N:14]3[CH2:19][CH:18]([CH:20]([CH3:22])[CH3:21])[NH:17][C:16](=[O:23])[CH2:15]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]4[CH2:19][CH:18]([CH:20]([CH3:22])[CH3:21])[NH:17][C:16](=[O:23])[CH2:15]4)[N:8]3[CH3:11])=[C:4]([N:24]3[CH2:25][CH2:26][O:27][CH2:28][CH2:29]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 59605276HCID 59605276, compound

Product 1

HCID 59606084HCID 59606084, compoundYield 44.8%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A mixture of 4-[2-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)ethyl]-6-isopropylpiperazin-2-one (90 mg, 0.21 mmol), 2-ethylbenzimidazole (35 mg, 0.24 mmol), Pd2(dba)3 (4.9 mg, 2.5 mol %), Xphos (10.2 mg, 10 mol %) and Cs2CO3 (104 mg, 0.32 mmol) in dioxane (2.0 mL) was purged with argon gas then heated at 120° C., for 19 h, in a sealed tube. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then the desired product eluted with 2 M NH3/MeOH in DCM. The resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient of acetonitrile 20-90%) to give 522 (50 mg, 44%) as a pale beige solid. LCMS: (Method I): RT 2.90 min; [M+H]+ 532.3. 1H NMR (400 MHz, CHCl3-d): δ 8.01-7.96 (m, 1 H), 7.84-7.78 (m, 1 H), 7.32-7.28 (m, 2 H), 5.82 (s, 1 H), 4.62-4.07 (m, 4 H), 3.86 (t, J=4.7 Hz, 4 H), 3.78 (s, 3 H), 3.47-3.23 (m, 4 H), 3.08-2.99 (m, 4 H), 3.01-2.93 (m, 2 H), 2.40 (dd, J=11.7, 8.9 Hz, 1 H), 1.79-1.67 (m, 1 H), 1.47 (t, J=7.5 Hz, 3 H), 0.98 (d, J=6.8 Hz, 3 H), 0.95 (d, J=6.88 Hz, 3 H)

Workup

  1. customwas purged with argon gas
  2. washwashed with MeOH
  3. washthe desired product eluted with 2 M NH3/MeOH in DCM
  4. customThe resulting residue was purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 20 mM triethylamine in water on a gradient of acetonitrile 20-90%)

Sources & evidence

ORD record
ord-827ca651fa9c47828668b9a64e789b68
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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