Sodium hydride → (6S)-6-[(4-bromopyridin-2-yl)methoxy]-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine

HRID 1446077Notes

Reaction equation

[N+:1]([C:4]1[N:5]=[C:6]2[N:11]([CH:12]=1)[CH2:10][C@H:9]([OH:13])[CH2:8][O:7]2)([O-:3])=[O:2].[Br:14][C:15]1[CH:20]=[CH:19][N:18]=[C:17]([CH2:21]Cl)[CH:16]=1.[H-].[Na+]>CN(C=O)C>[Br:14][C:15]1[CH:20]=[CH:19][N:18]=[C:17]([CH2:21][O:13][C@@H:9]2[CH2:8][O:7][C:6]3=[N:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:12][N:11]3[CH2:10]2)[CH:16]=1

Participants

Conditions

Temperature: 2.5 °C

Procedure

A solution of (S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxa-zin-6-ol (2.87 g, 15.5 mmol) and 4-bromo-2-(chloromethyl)pyridine (2.91 g, 14 mmol) in dry DMF (60 mL) was treated with NaH (0.68 g of a 60% dispersion in mineral oil, 16.9 mmol,) at 0-5° C., and the mixture was stirred at room temperature for 3 h, then quenched with water (150 mL) and extracted with EtOAc (6×150 mL). The organic layers were dried (MgSO4), evaporated, and chromatographed on silica gel, eluting with MeOH/EtOAc (1:19), to give the title compound (2.701 g, 54%) as a light yellow solid. APCI MS m/z 355.7, 357.7 (M+H). 1H NMR (400 MHz, (CD3)2SO) 68.41 (d, J=5.3 Hz, 1H), 8.01 (s, 1H), 7.59 (dd, J=5.3, 1.9 Hz, 1H), 7.55 (d, J=1.5 Hz, 1H), 4.78-4.68 (m, 3H), 4.50 (d, J=12.0 Hz, 1H), 4.35-4.22 (m, 3H).

Workup

customquenched with water (150 mL)
extractionextracted with EtOAc (6×150 mL)
dry with materialThe organic layers were dried (MgSO4)
customevaporated
customchromatographed on silica gel
washeluting with MeOH/EtOAc (1:19)

Sources & evidence

ORD record: ord-8d4a6c08f16c4f23b536e9c8a45b2195
Source dataset: uspto-grants-2010_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07666864B2

Reaction notes

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