N,N,N',N'-Tetramethylethylenediamine → 4-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbonyl]piperidine-1-carboxylic acid tert-butyl ester

HRID 1945682Notes

Reaction equation

HRID 1945682 reaction equation
[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[CH:13][N:14]3[CH3:17])=[C:10]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[N:9]=2)[C:6]2[CH:24]=[CH:25][CH:26]=[CH:27][C:5]=2[N:4]=1)[CH3:2].CN(CCN(C)C)C.[Li]CCCC.[C:41]([O:45][C:46]([N:48]1[CH2:53][CH2:52][CH:51]([C:54](=[O:59])NCOC)[CH2:50][CH2:49]1)=[O:47])([CH3:44])([CH3:43])[CH3:42]>C1COCC1>[C:41]([O:45][C:46]([N:48]1[CH2:53][CH2:52][CH:51]([C:54]([C:13]2[N:14]([CH3:17])[C:15]3[C:11]([N:12]=2)=[C:10]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[N:9]=[C:8]([N:7]2[C:6]4[CH:24]=[CH:25][CH:26]=[CH:27][C:5]=4[N:4]=[C:3]2[CH2:1][CH3:2])[N:16]=3)=[O:59])[CH2:50][CH2:49]1)=[O:47])([CH3:44])([CH3:43])[CH3:42]

Participants

6

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 442032024-(Methoxymethylcarbamoyl)piperidine-1-carboxylic acid tert-butyl esterHCID 596054942-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purineHCID 178418339Butyllithium

Product 1

HCID 596054014-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbonyl]piperidine-1-carboxylic acid tert-butyl esterYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine (500 mg, 1.38 mmol) and TMEDA (312 μL, 2.07 mmol) in THF (10 mL) at −78° C. was added n-BuLi (660 μL, 1.65 mmol, 2.5M solution in hexanes) and the resulting mixture stirred for 30 min before the addition of a solution of 4-(methoxymethylcarbamoyl)piperidine-1-carboxylic acid tert-butyl ester (564 mg, 2.07 mmol) in THF (5 mL). The resulting mixture was stirred for 2 h then quenched with H2O and extracted with EtOAc. The combined organic phases were dried (MgSO4) and concentrated in vacuo. The resulting residue was triturated with EtOAc:cyclohexane and the mother liquors concentrated in vacuo affording the title compound as an oil (760 mg, 96%). LCMS (method A): RT 3.67 min [M+H]+ 557.3

Workup

  1. customthen quenched with H2O
  2. extractionextracted with EtOAc
  3. dry with materialThe combined organic phases were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was triturated with EtOAc
  6. concentrationcyclohexane and the mother liquors concentrated in vacuo

Sources & evidence

ORD record
ord-fab381d3539640b6a0e8e24b19534839
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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