Cesium carbonate → HCID 59605502, compound

HRID 1946056Notes

Reaction equation

HRID 1946056 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][CH2:13][N:14]3[CH2:17][CH:16]([N:18]4[CH2:23][CH2:22][S:21](=[O:25])(=[O:24])[CH2:20][CH2:19]4)[CH2:15]3)[N:8]2[CH3:11])=[C:4]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[N:3]=1.[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.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]>[CH2:32]([C:34]1[N:35]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[C:7]([CH2:12][CH2:13][N:14]4[CH2:15][CH:16]([N:18]5[CH2:23][CH2:22][S:21](=[O:24])(=[O:25])[CH2:20][CH2:19]5)[CH2:17]4)[N:8]3[CH3:11])=[C:4]([N:26]3[CH2:27][CH2:28][O:29][CH2:30][CH2:31]3)[N:3]=2)[C:36]2[CH:42]=[CH:41][CH:40]=[CH:39][C:37]=2[N:38]=1)[CH3:33]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86648269HCID 86648269, compound

Product 1

HCID 59605502HCID 59605502, compoundYield 69%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A mixture of 2-chloro-8-{2-[3-(1,1-dioxo-1-thiomorpholin-4-yl)azetidin-1-yl]-ethyl}-9-methyl-6-morpholin-4-yl-9H-purine (93 mg, 0.20 mmol), 2-ethylbenzimidazole (32 mg, 0.22 mmol), Pd2(dba)3 (4.5 mg, 2.5 mol %), Xphos (9.4 mg, 10 mol %) and Cs2CO3 (97 mg, 0.30 mmol) in dioxane (2.0 mL) was purged with argon gas then heated at 120° C., for 20 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 537 (79 mg, 69%) as a beige solid. LCMS: (Method I): RT 2.42 min; [M+H]+ 580.3. 1H NMR (400 MHz, CHCl3-d): δ 8.01-7.96 (m, 1 H), 7.77-7.72 (m, 1 H), 7.29-7.22 (m, 2 H), 4.57-4.09 (m, 4 H), 3.86 (t, J=4.8 Hz, 4 H), 3.77 (s, 3 H), 3.71-3.57 (m, 2 H), 3.34 (q, J=7.5 Hz, 2 H), 3.33-3.22 (m, 1 H), 3.07 (m, 8 H), 3.00-2.89 (m, 2 H), 2.85 (t, J=4.8 Hz, 4 H), 1.44 (t, J=7.5 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-2789031a0299433abcd87bc48efa806b
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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