Cesium carbonate → tert-butyl 4-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)(hydroxy)methyl)piperidine-1-carboxylate

HRID 1923222Notes

Reaction equation

HRID 1923222 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH:12]([OH:26])[CH:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)[N:8]2[CH3:11])=[C:4]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)[N:3]=1.[CH2:33]([C:35]1[NH:36][C:37]2[CH:43]=[CH:42][CH:41]=[CH:40][C:38]=2[N:39]=1)[CH3:34].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+]>CN(C=O)C.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]>[CH2:33]([C:35]1[N:36]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[C:7]([CH:12]([OH:26])[CH:13]4[CH2:14][CH2:15][N:16]([C:19]([O:21][C:22]([CH3:24])([CH3:23])[CH3:25])=[O:20])[CH2:17][CH2:18]4)[N:8]3[CH3:11])=[C:4]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[N:3]=2)[C:37]2[CH:43]=[CH:42][CH:41]=[CH:40][C:38]=2[N:39]=1)[CH3:34]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 59605210tert-butyl 4-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)(hydroxy)methyl)piperidine-1-carboxylate

Product 1

HCID 67492684tert-butyl 4-((2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)(hydroxy)methyl)piperidine-1-carboxylateYield 69.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of tert-butyl 4-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)(hydroxy)methyl)piperidine-1-carboxylate (0.375 g, 0.803 mmol), 2-ethylbenzimidazole (0.182 g, 1.23 mmol), Xphos (0.040 g, 0.084 mmol), Pd2(dba)3 (0.040 g, 0.042 mmol) and cesium carbonate (0.52 g, 1.67 mmol) in DMF (4.0 mL) was heated in a Biotage microwave at 140° C. for 30 minutes. The reaction mixture was then filtered through paper and then partitioned between brine and EtOAc. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography (0-5% MeOH in DCM) to give the title compound (0.32 g, 69%). LCMS m/z: 577.2 (MH+).

Workup

  1. filtrationThe reaction mixture was then filtered through paper
  2. custompartitioned between brine and EtOAc
  3. washThe combined extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography (0-5% MeOH in DCM)

Sources & evidence

ORD record
ord-7488575ff8a44ca795361daad197be36
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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