Acetone → 2-{4-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]piperidin-1-yl}-2-methylpropionitrile

HRID 1946122Notes

Reaction equation

HRID 1946122 reaction equation
Cl.[CH2:2]([C:4]1[N:8]([C:9]2[N:17]=[C:16]3[C:12]([N:13]=[C:14]([CH:19]4[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]4)[N:15]3[CH3:18])=[C:11]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[N:10]=2)[C:7]2[CH:31]=[CH:32][CH:33]=[CH:34][C:6]=2[N:5]=1)[CH3:3].Cl.[C-:36]#[N:37].[Na+].CC(=O)C.[CH2:43]1[CH2:47]OC[CH2:44]1>O>[CH2:2]([C:4]1[N:8]([C:9]2[N:17]=[C:16]3[C:12]([N:13]=[C:14]([CH:19]4[CH2:20][CH2:21][N:22]([C:43]([CH3:44])([CH3:47])[C:36]#[N:37])[CH2:23][CH2:24]4)[N:15]3[CH3:18])=[C:11]([N:25]3[CH2:26][CH2:27][O:28][CH2:29][CH2:30]3)[N:10]=2)[C:7]2[CH:31]=[CH:32][CH:33]=[CH:34][C:6]=2[N:5]=1)[CH3:3]

Participants

7

Reactant 5

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 8929Sodium CyanideHCID 674922312-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-8-piperidin-4-yl-9H-purine hydrochloride

Product 1

HCID 596055752-{4-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]piperidin-1-yl}-2-methylpropionitrileYield 69%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-8-piperidin-4-yl-9H-purine hydrochloride (396 mg, 0.89 mmol) in THF (3 mL) and H2O (4 mL) was added 1M HCl to give pH 4 followed by NaCN (261 mg, 5.32 mmol) and propan-2-one (590 μL, 7.98 mmol). The resulting mixture was allowed to stir at r.t. for 16 h then partitioned between H2O and DCM. The organic phase was dried (phase separator) and concentrated in vacuo. The resulting residue was triturated with Et2O and the solid collected by filtration and dried in vacuo affording 2-{4-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]piperidin-1-yl}-2-methylpropionitrile (316 mg, 69%). LCMS (method H): RT 2.64 min, [M+H]+ 514.4

Workup

  1. customto give pH 4
  2. customthen partitioned between H2O and DCM
  3. customThe organic phase was dried (phase separator)
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was triturated with Et2O
  6. filtrationthe solid collected by filtration
  7. customdried in vacuo

Sources & evidence

ORD record
ord-8d262cbd2a124a78a2300d91d78f142e
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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