Water → HCID 178461553, compound

HRID 522812Notes

Reaction equation

Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7](C3C=CC=C4C=3C=CN4)[NH:8]2)=[C:4]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][C@H:21]2C)[N:3]=1.[O:27]1[CH2:33][CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.[CH3:34]CN(C(C)C)C(C)C.O>C(O)CCC>[CH3:34][C@@H:28]1[O:27][C@H:33]([CH3:32])[CH2:31][N:30]([C:2]2[N:10]=[C:9]3[C:5]([N:6]=[CH:7][NH:8]3)=[C:4]([N:20]3[CH2:21][CH2:22][O:23][CH2:24][CH2:25]3)[N:3]=2)[CH2:29]1

Participants

Conditions

Temperature: 120 °C

Procedure

To the solution of 2-chloro-8-(1H-indol-4-yl)-6-((R)-3-methyl-morpholin-4-yl)-9H-purine (50 mg, 0.14 mmol) in 1-butanol (300 μL) was added 1,4-oxazepane (20.6 mg, 0.20 mmol), followed by DIPEA (47.4 μL, 0.27 mmol). The mixture was stirred at 120° C. for 24 hours. Upon completion of the reaction, the solution was poured into water. The aqueous layer was extracted with CH2Cl2 three times. The combined organic layers were dried over Na2SO4, filtered, concentrated under reduced pressure and the crude was purified by flash column chromatography (30-100% EtOAc/cyclohexane gradient) to provide 2-((2S,6R)-2,6-dimethyl-morpholin-4-yl)-6-morpholin-4-yl-9H-purine (35 mg, 59%) as a beige solid. LC-MS at 254 nm; [M+H] 432.3; Rt 1.00 min; (LCMS method 1).

Workup

customUpon completion of the reaction
extractionThe aqueous layer was extracted with CH2Cl2 three times
dry with materialThe combined organic layers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customthe crude was purified by flash column chromatography (30-100% EtOAc/cyclohexane gradient)

Sources & evidence

ORD record: ord-37f2b30fc4ee4019a1389f24dd1dcbfa
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09334271B2

Reaction notes

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