Hydrochloric Acid → 2-Chloro-9-methyl-6-((S)-3-methylmorpholin-4-yl)-9H-purine-8-carbaldehyde

HRID 1945700Notes

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][C@@H:13]2[CH3:18])[N:3]=1.CN(CCN(C)C)C.[Li]CCCC.CN([CH:35]=[O:36])C.Cl>C1COCC1>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH:35]=[O:36])[N:8]2[CH3:11])=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][C@@H:13]2[CH3:18])[N:3]=1

Participants

Conditions

Temperature: -40 °C

Procedure

To a solution of 2-chloro-9-methyl-6-((S)-3-methylmorpholin-4-yl)-9H-purine (500 mg, 1.67 mmol) and TMEDA (419 μL, 2.80 mmol) in THF (10 mL) at −78° C. was added n-BuLi (1.12 mL, 2.80 mmol, 2.5M solution in hexanes). The resulting mixture was allowed to warm to −40° C. and stir for 30 min then cooled back to −78° C. before the addition of DMF (435 μL, 5.61 mmol). The reaction mixture was allowed to stir at −78° C. for 30 min then poured onto 1M HCl. The aqueous phase was extracted with EtOAc and the combined organic phases were washed with H2O and brine, then dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 0-50%) affording the title compound as a white solid (450 mg, 81%). LCMS (method H): RT 3.28 min [M+H]+ 296.3

Workup

stirringto stir at −78° C. for 30 min
extractionThe aqueous phase was extracted with EtOAc
washthe combined organic phases were washed with H2O and brine
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
customThe resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 0-50%)

Sources & evidence

ORD record: ord-a529b28a37244ecb8bbc55718ab35df0
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08394796B2

Reaction notes

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