Hydrochloric Acid → HCID 59606042, compound

HRID 1945696Notes

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[CH:17]3[CH2:18][CH2:19][CH:13]2[CH2:14][O:15][CH2:16]3)[N:3]=1.CN(CCN(C)C)C.[Li]CCCC.CN([CH:36]=[O:37])C.Cl>C1COCC1>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH:36]=[O:37])[N:8]2[CH3:11])=[C:4]([N:12]2[CH:17]3[CH2:18][CH2:19][CH:13]2[CH2:14][O:15][CH2:16]3)[N:3]=1

Participants

Conditions

Temperature: -40 °C

Procedure

To a solution of 2-chloro-9-methyl-6-(3-oxa-8-azabicyclo[3.2.1]oct-8-yl)-9H-purine (620 mg, 2.22 mmol) and TMEDA (498 μL, 3.33 mmol) in THF (11 mL) at −78° C. was added n-BuLi (1.3 mL, 3.33 mmol, 2.5M solution in hexanes). The resulting mixture was warmed to −40° C. and allowed to stir for 30 min before cooling back to −78° C. DMF (517 μL, 6.65 mmol) was added and the resulting mixture was stirred at −78° C. for 30 min then poured onto 1M HCl. The aqueous layer was extracted with EtOAc and the organic phase washed with brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%) affording the title compound as a pale yellow solid (500 mg, 73%). 1H NMR (CDCl3, 400 MHz): δ 9.88 (1 H, s), 5.79 (1 H, d, J=6.14 Hz), 5.05 (1 H, d, J=6.84 Hz), 4.05 (3 H, s), 3.80-3.78 (4 H, m), 2.29-2.01 (4 H, m)

Workup

temperaturebefore cooling back to −78° C
stirringthe resulting mixture was stirred at −78° C. for 30 min
extractionThe aqueous layer was extracted with EtOAc
washthe organic phase washed with brine
dry with materialdried (Na2SO4)
concentrationconcentrated in vacuo
customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%)

Sources & evidence

ORD record: ord-5c79c1b399e24b349ce9168eb9a9a7aa
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08394796B2

Reaction notes

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