Dimethylformamide → 2-chloro-6-morpholin-4-yl-9-(tetrahydropyran-2-yl)-9H-purine-8-carbaldehyde

HRID 1692873

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.[Li]CCCC.CN([CH:31]=[O:32])C>C1COCC1>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH:31]=[O:32])[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: -78 °C

Procedure

To a solution of 4-(2-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)morpholine (1.96 g, 6.05 mmol) in THF (75 mL) was a 2.5 M solution of n-BuLi in hexanes (3.2 mL, 7.9 mmol) at −78° C. The reaction mixture was then stirred at −78° C. for 45 minutes. DMF (0.94 mL, 12.1 mmol) was then added. The resulting mixture was stirred at −78° C. for 2 hours before being poured slowly onto ice. The mixture was then extracted three times with DCM. The combined extracts were washed with water, dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography (25% EtOAc in heptane) to give the title compound (1.1 g, 52%). LCMS: M+H+=352.2.

Workup

customat −78° C
stirringThe resulting mixture was stirred at −78° C. for 2 hours
additionbefore being poured slowly onto ice
extractionThe mixture was then extracted three times with DCM
washThe combined extracts were washed with water
dry with materialdried over sodium sulfate
concentrationconcentrated
customThe crude product was purified by flash chromatography (25% EtOAc in heptane)

Sources & evidence

ORD record: ord-e94d3b798b994686aeaffefe6aaaee63
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08158625B2

Linked notes

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