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

HRID 1922840Notes

Reaction equation

[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[N:3]=1.CN(CCN(C)C)C.[Li]CCCC.ClCC[I:39]>C1COCC1>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([I:39])[N:8]2[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[C:4]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[N:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 2-chloro-6-morpholin-4-yl-9-(tetrahydropyran-2-yl)-9H-purine (1.50 g, 4.63 mmol) and TMEDA (1.72 mL, 6.94 mmol) in THF (30 mL) was cooled to −78° C. before the drop wise addition of n-BuLi (6.08 mL, 9.73 mmol, 1.6 M solution in hexanes). The resulting mixture was allowed to stir at −78° C. for 485 min before the addition of 1-chloro-2-iodoethane (902 μL, 16.22 mmol). The resulting mixture was allowed to warm to 0° C. over 2.5 h then quenched with H2O and extracted with DCM. The combined organics were washed with brine then dried (Na2SO4) and concentrated in vacuo. The residue was triturated with iPrOAc and the resulting solid collected by filtration affording the title compound (1.80 g, 87%). LCMS (method A): RT 3.90 min [M+H]+ 450.3

Workup

customthen quenched with H2O
extractionextracted with DCM
washThe combined organics were washed with brine
dry with materialthen dried (Na2SO4)
concentrationconcentrated in vacuo
customThe residue was triturated with iPrOAc
filtrationthe resulting solid collected by filtration

Sources & evidence

ORD record: ord-61aa662e761a4c23895865af08ccfe0f
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08173650B2

Reaction notes

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