Sodium hydride → (6S)-6-[(6-Chloro-3-pyridazinyl)methoxy]-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine

HRID 1446079Notes

Reaction equation

[H-].[Na+].[N+:3]([C:6]1[N:7]=[C:8]2[N:13]([CH:14]=1)[CH2:12][C@H:11]([OH:15])[CH2:10][O:9]2)([O-:5])=[O:4].Br[CH2:17][C:18]1[N:19]=[N:20][C:21]([Cl:24])=[CH:22][CH:23]=1>CN(C=O)C>[Cl:24][C:21]1[N:20]=[N:19][C:18]([CH2:17][O:15][C@@H:11]2[CH2:10][O:9][C:8]3=[N:7][C:6]([N+:3]([O-:5])=[O:4])=[CH:14][N:13]3[CH2:12]2)=[CH:23][CH:22]=1

Participants

Conditions

Temperature: -42 °C

Procedure

Sodium hydride (60% w/w, 0.30 g, 7.6 mmol) was added to a solution of (6S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-ol (0.89 g, 4.8 mmol) in DMF (20 mL) at 0° C. The resultant solution was cooled to −42° C. and a solution of 3-(bromomethyl)-6-chloropyridazine (1.05 g, 5.1 mmol) in DMF (5 mL) was added. The mixture was stirred at −42° C. for 1 h and then quenched with ice. EtOAc (200 mL) was added, the organic layer was dried (MgSO4) and concentrated under reduced pressure. The residue was chromatographed on silica gel, initially eluting with hexanes/EtOAc (1:1) to remove unreacted 3-(bromomethyl)-6-chloropyridazine and then EtOAc to give the title compound (0.84 g, 56%) as a white solid. APCI MS m/z 312.6 (M+H). 1H NMR (400 MHz, (CD3)2SO) δ 8.02 (s, 1H), 7.93 (d, J=8.8 Hz, 1H), 7.74 (d, J=8.8 Hz, 1H), 4.97 (d, J=13.2 Hz, 1H), 4.94 (d, J=13.2 Hz, 1H), 4.69 (dt, J=12.0, 2.6 Hz, 1H), 4.50 (d, J=12.1 Hz, 1H), 4.30-4.39 (m, 2H), 4.25 (dd, J=13.5, 3.3 Hz, 1H).

Workup

customquenched with ice
additionEtOAc (200 mL) was added
dry with materialthe organic layer was dried (MgSO4)
concentrationconcentrated under reduced pressure
customThe residue was chromatographed on silica gel
washinitially eluting with hexanes/EtOAc (1:1)
customto remove unreacted 3-(bromomethyl)-6-chloropyridazine

Sources & evidence

ORD record: ord-2b946b02148241dc95d26731020b6f12
Source dataset: uspto-grants-2010_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07666864B2

Reaction notes

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