Sodium hydride → 4-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethyl]-2-isopropyl-3-oxopiperazine-1-carboxylic acid tert-butyl ester

HRID 1945665Notes

Reaction equation

HRID 1945665 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][C:10](=[O:14])[CH:9]1[CH:15]([CH3:17])[CH3:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:21][C:22]1[N:23]([CH3:48])[C:24]2[C:29]([N:30]=1)=[C:28]([N:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1)[N:27]=[C:26]([N:37]1[C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=3[N:39]=[C:38]1[CH2:46][CH3:47])[N:25]=2>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:21][C:22]2[N:23]([CH3:48])[C:24]3[C:29]([N:30]=2)=[C:28]([N:31]2[CH2:32][CH2:33][O:34][CH2:35][CH2:36]2)[N:27]=[C:26]([N:37]2[C:41]4[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=4[N:39]=[C:38]2[CH2:46][CH3:47])[N:25]=3)[C:10](=[O:14])[CH:9]1[CH:15]([CH3:17])[CH3:16])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 674922148-bromomethyl-2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purineHCID 67492477HCID 67492477, compound

Product 1

HCID 596060354-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-ylmethyl]-2-isopropyl-3-oxopiperazine-1-carboxylic acid tert-butyl esterYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 2-isopropyl-3-oxopiperazine-1-carboxylic acid tert-butyl ester (58 mg, 0.24 mmol) in DMF (1.5 mL) at 0° C. was added NaH (11 mg, 0.29 mmol, 60% dispersion in mineral oil) and the resulting mixture stirred at r.t. for 30 min before the addition of 8-bromomethyl-2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine (100 mg, 0.22 mmol) in DMF (1.5 mL). The resulting mixture was allowed to stir for 19 h then partitioned between EtOAc and H2O. The organic phase was dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-10%) affording the title compound as a yellow oil (104 mg, 77%), LCMS (method H): RT 3.03 min [M+H]+ 618.4

Workup

  1. customthen partitioned between EtOAc and H2O
  2. dry with materialThe organic phase was dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-10%)

Sources & evidence

ORD record
ord-34990ffcfe794cd3b4bacfe3f0d1bf58
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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