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

HRID 1446079노트

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HRID 1446079 반응식
[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

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 10130259(S)-2-nitro-6,7-dihydro-5H-imidazo(2,1-b)(1,3)oxazin-6-olHCID 230809253-(Bromomethyl)-6-chloropyridazine

생성물 1

HCID 49852044(6S)-6-[(6-Chloro-3-pyridazinyl)methoxy]-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine수율 56.1%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

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온도
-42 °C

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-2b946b02148241dc95d26731020b6f12
출처 데이터셋
uspto-grants-2010_02
특허 번호
US07666864B2

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