Cesium carbonate → HCID 59605327, compound

HRID 1945920Notes

Reaction equation

HRID 1945920 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][CH2:18][N:17]([C:20]([CH3:25])([CH3:24])[C:21]([NH2:23])=[O:22])[CH2:16][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.[CH3:32][C:33]1[NH:34][C:35]2[CH:41]=[CH:40][CH:39]=[CH:38][C:36]=2[N:37]=1.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]>[CH3:24][C:20]([N:17]1[CH2:16][CH2:15][N:14]([CH2:13][CH2:12][C:7]2[N:8]([CH3:11])[C:9]3[C:5]([N:6]=2)=[C:4]([N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[N:3]=[C:2]([N:34]2[C:35]4[CH:41]=[CH:40][CH:39]=[CH:38][C:36]=4[N:37]=[C:33]2[CH3:32])[N:10]=3)[CH2:19][CH2:18]1)([CH3:25])[C:21]([NH2:23])=[O:22]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 119842-MethylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 59605461HCID 59605461, compound

Product 1

HCID 59605327HCID 59605327, compoundYield 65%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A mixture of 2-{4-[2-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)ethyl]piperazin-1-yl}isobutyramide (80 mg, 0.18 mmol), 2-methylbenzimidazole (26 mg, 0.20 mmol), Pd2(dba)3 (4 mg, 2.5 mol %), Xphos (8 mg, 10 mol %) and Cs2CO3 (87 mg, 0.27 mmol) in dioxane (1.0 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 in MeOH. The resulting residue was purified by flash chromatography (Si—PCC, 0-10% MeOH in DCM) to give 368 (63 mg, 65%) as a pale yellow solid. LCMS: (Method G): RT 5.34 min; [M+H]+ 547.3. 1H NMR (400 MHz, CHCl3-d): δ 8.09-8.05 (m, 1 H), 7.73-7.69 (m, 1 H), 7.29-7.24 (m, 1 H), 7.06 (s, 1 H), 5.23 (s, 1 H), 4.47-4.14 (m, 4 H), 3.87 (t, J=4.7 Hz, 4 H), 3.79 (s, 3 H), 3.49 (s, 1 H), 3.19-3.0 (m, 2 H), 2.94 (s, 3 H), 2.78-2.54 (m, 6 H), 1.78-1.48 (m, 4 H), 1.25 (s, 6 H)

Workup

  1. customwas purged with argon gas
  2. washwashed with MeOH
  3. washthe desired product eluted with 2 M NH3 in MeOH
  4. customThe resulting residue was purified by flash chromatography (Si—PCC, 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-72a1ad688b494f49b2e8976a32e0f8cc
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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