N,N,N',N'-Tetramethylethylenediamine → 2-Chloro-8-iodo-9-methyl-6-morpholin-4-yl-9H-purine

HRID 1945656Notes

Reaction equation

HRID 1945656 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH3:11])=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[N:3]=1.CN(CCN(C)C)C.[Li]CCCC.ClCC[I:34]>C1COCC1>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([I:34])[N:8]2[CH3:11])=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[N:3]=1

Participants

6

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 1364381-Chloro-2-iodoethaneHCID 715006872-Chloro-9-methyl-6-(4-morpholinyl)-9H-purineHCID 178418339Butyllithium

Product 1

HCID 596059622-Chloro-8-iodo-9-methyl-6-morpholin-4-yl-9H-purineYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

A suspension of 2-chloro-9-methyl-6-morpholin-4-yl-9H-purine (2.95 g, 11.7 mmol) and TMEDA (2.6 mL, 2.03 g, 17.5 mmol) in THF (80 mL) was cooled to −78° C. before the drop wise addition of n-BuLi (9.8 mL, 24.5 mmol, 2.5 M solution in hexanes). The resulting mixture was warmed to −40° C. and stirred for 40 mins. The mixture was cooled back to −78° C. before the addition of 1-chloro-2-iodoethane (3.7 mL, 7.8 g, 40.8 mmol). The resulting mixture was allowed to warm to r.t. over 2 h then quenched with NH4Cl and extracted with EtOAc (×4). The combined organics were dried (Na2SO4) and concentrated in vacuo affording 2-Chloro-8-iodo-9-methyl-6-morpholin-4-yl-9H-purine as a yellow solid (4.02 g, 91%). LCMS (method H): RT 4.09 min [M+H]+ 379.9

Workup

  1. temperatureto warm to r.t. over 2 h
  2. customthen quenched with NH4Cl
  3. extractionextracted with EtOAc (×4)
  4. dry with materialThe combined organics were dried (Na2SO4)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3e909aa8a4f642d79cda83107a3c937b
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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