Methanesulfonic Acid → Dolutegravir Impurity 36

HRID 1505822Notes

Reaction equation

[F:1][C:2]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:3]=1[CH2:4][NH:5][C:6]([C:8]1[C:9](=[O:26])[C:10]([O:24][CH3:25])=[C:11]([C:20]([O:22][CH3:23])=[O:21])[N:12]([CH2:14][CH:15]([O:18]C)[O:16]C)[CH:13]=1)=[O:7].CS(O)(=O)=O>C(#N)C.C(O)(=O)C>[F:1][C:2]1[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:3]=1[CH2:4][NH:5][C:6]([C:8]1[C:9](=[O:26])[C:10]([O:24][CH3:25])=[C:11]([C:20]([O:22][CH3:23])=[O:21])[N:12]([CH2:14][CH:15]([OH:18])[OH:16])[CH:13]=1)=[O:7]

Participants

Conditions

Temperature: 70 °C

Procedure

Methyl 5-(2,4-difluorobenzylcarbamoyl)-1-(2,2-dimethoxyethyl)-3-methoxy-4-oxo-1,4-dihydropyridine-2-carboxylate (1-B, 0.106 g, 0.24 mmol) in acetonitrile (0.9 mL) and acetic acid (0.1 mL) was treated with methanesulfonic acid (0.005 mL, 0.072 mmol), sealed with a yellow cap, and heated to 70° C. After 16 hours, the mixture was cooled to afford a crude solution of methyl 5-(2,4-difluorobenzylcarbamoyl)-1-(2,2-dihydroxyethyl)-3-methoxy-4-oxo-1,4-dihydropyridine-2-carboxy late, 1-C. LCMS-ESI+ (m/z): [M+H]+ calculated for C18H19F2N2O7: 413.12; found: 413.1.

Workup

customsealed with a yellow cap
temperaturethe mixture was cooled

Sources & evidence

ORD record: ord-9480c21130fd460cb01fddfeb4642d7a
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216996B2

Reaction notes

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