Hydrochloric Acid → 1-methyl-2-{[1-(2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)piperidin-4-yl]oxy}-1H-[4,4']bipyrimidinyl-6-one

HRID 1468782Notes

Reaction equation

[CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[C:5]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][N:10]=2)[N:4]=[C:3]1[O:15][CH:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:23]=[CH:24][C:25]3[N:30](COCC[Si](C)(C)C)[C:29](=[O:39])[O:28][CH2:27][C:26]=3[CH:40]=2)[CH2:18][CH2:17]1.Cl.O.C(=O)([O-])O.[Na+]>O1CCCC1>[CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[C:5]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][N:10]=2)[N:4]=[C:3]1[O:15][CH:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:23]=[CH:24][C:25]3[NH:30][C:29](=[O:39])[O:28][CH2:27][C:26]=3[CH:40]=2)[CH2:18][CH2:17]1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 1-methyl-2-{[1-(2-oxo-1{[2-(trimethylsilyl)ethoxy]methyl}-1,4-dihydro-2H-3,1-benzoxazin-6-yl)piperidin-4-yl]oxy}-1H-[4,4′]bipyrimidinyl-6-one (78 mg, 0.14 mmol) in tetrahydrofuran (1.4 ml) was added 6N aqueous hydrochloric acid (1.4 ml, 8.4 mmol). The mixture was stirred at 70° C. for 3 hours. The mixture was poured into water. The aqueous solution was neutralized with sodium hydrogen carbonate. Extraction with dichloromethane was performed three times. The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluent; chloroform/methanol=98/2) to afford 1-methyl-2-{[1-(2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)piperidin-4-yl]oxy}-1H-[4,4′]bipyrimidinyl-6-one as a pale yellow solid (22 mg, 0.051 mmol, 38%).

Workup

extractionExtraction with dichloromethane
dry with materialThe organic layer was dried over sodium sulfate
concentrationconcentrated in vacuo
customThe residue was purified by silica gel column chromatography (eluent; chloroform/methanol=98/2)

Sources & evidence

ORD record: ord-a70659b8e5af4006971f8fb1139a386c
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09006232B2

Reaction notes

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