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Potassium Carbonate → 4-(((6-Methoxy-2-(6-methylimidazo[1,2-b]pyridazin-2-yl)benzofuran-4-yl)oxy)methyl)-2-phenylthiazole

HRID 1424377
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HRID 1424377 반응식
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[O:9][C:8]([C:10]3[N:11]=[C:12]4[CH:17]=[CH:16][C:15]([CH3:18])=[N:14][N:13]4[CH:19]=3)=[CH:7][C:6]2=[C:20]([OH:22])[CH:21]=1.Br[CH2:24][C:25]1[N:26]=[C:27]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[S:28][CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:21]=[C:20]([O:22][CH2:24][C:25]2[N:26]=[C:27]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[S:28][CH:29]=2)[C:6]2[CH:7]=[C:8]([C:10]3[N:11]=[C:12]4[CH:17]=[CH:16][C:15]([CH3:18])=[N:14][N:13]4[CH:19]=3)[O:9][C:5]=2[CH:4]=1
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참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 665984924-(Bromomethyl)-2-phenylthiazoleHCID 867009166-Methoxy-2-(6-methylimidazo[1,2-b]pyridazin-2-yl)benzofuran-4-ol

생성물 1

HCID 867009184-(((6-Methoxy-2-(6-methylimidazo[1,2-b]pyridazin-2-yl)benzofuran-4-yl)oxy)methyl)-2-phenylthiazole수율 66%

시약·촉매·용매 2

HCID 6228
Dimethylformamide
용매
HCID 6344Dichloromethane용매

반응 조건

온도
22 °C

실험 절차

In a 100 mL round-bottom flask, a suspension of 6-methoxy-2-(6-methylimidazo[1,2-b]pyridazin-2-yl)benzofuran-4-ol (Example 39B, 0.190 g, 0.643 mmol) and 4-(bromomethyl)-2-phenylthiazole (Table of bromides, 0.180 g, 0.708 mmol) in DMF (5 mL) was purged under vacuum and N2 for 10 min. The reaction was treated with potassium carbonate (0.24 g, 1.737 mmol) and stirred at 22° C. for 18 hours, then diluted with DCM and washed with water (1×), brine (1×). The organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (2.5×10 cm, 0% to 50% EtOAc in CH2Cl2) to give the impure title material (0.198 g, 66%). The solid was triturated in hot ethyl acetate to provide the pure title material (0.176 g). LC (Method A): 2.414 min. HRMS (ESI) calcd for C26H21N4O3S [M+H]+ m/z 469.1329. found 469.1379. 1H NMR (CDCl3, 400 MHz) δ ppm: 2.57 (s, 3H), 3.84 (s, 3H), 5.39 (s, 2H), 6.46 (d, J=1.96 Hz, 1H), 6.74 (broad d, 1H), 6.91 (d, J=9.1 Hz, 1H), 7.34 (s, 1H), 7.36 (s, 1H), 7.39-7.46 (m, 3H), 7.80 (d, J=9.1 Hz, 1H), 7.90-8.0 (m, 2H), 8.19 (s, 1H).

후처리

  1. customwas purged under vacuum and N2 for 10 min
  2. washwashed with water (1×), brine (1×)
  3. dry with materialThe organic layers were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography (2.5×10 cm, 0% to 50% EtOAc in CH2Cl2)

출처 및 근거

ORD 기록
ord-944ee1bf29c542ad91b8c437ef18a1cb
출처 데이터셋
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08927688B2

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