Cesium carbonate → 3-{7-[(5-bromopyridin-2-yl)oxy]-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl}-4-hydroxy-1-(isobutylamino)quinolin-2(1H)-one

HRID 601373노트

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HRID 601373 반응식
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([NH:12][CH2:13][CH:14]([CH3:16])[CH3:15])[C:4](=[O:17])[C:3]=1[C:18]1[NH:23][C:22]2[CH:24]=[CH:25][C:26]([OH:28])=[CH:27][C:21]=2[S:20](=[O:30])(=[O:29])[N:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:38]1[CH:43]=[CH:42][C:41]([Br:44])=[CH:40][N:39]=1>CS(C)=O>[Br:44][C:41]1[CH:42]=[CH:43][C:38]([O:28][C:26]2[CH:25]=[CH:24][C:22]3[NH:23][C:18]([C:3]4[C:4](=[O:17])[N:5]([NH:12][CH2:13][CH:14]([CH3:15])[CH3:16])[C:6]5[C:11]([C:2]=4[OH:1])=[CH:10][CH:9]=[CH:8][CH:7]=5)=[N:19][S:20](=[O:29])(=[O:30])[C:21]=3[CH:27]=2)=[N:39][CH:40]=1

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 693532,5-DibromopyridineHCID 1363584044-hydroxy-3-(7-hydroxy-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-1-(isobutylamino)quinolin-2(1H)-one

생성물 1

HCID 1363584293-{7-[(5-bromopyridin-2-yl)oxy]-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl}-4-hydroxy-1-(isobutylamino)quinolin-2(1H)-one수율 64.6%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

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온도
110 °C

실험 절차

A mixture of the product of Example 321C (40.0 mg, 0.09 mmol), cesium carbonate (112 mg, 0.34 mmol), and 2,5-dibromopyridine (40.0 mg, 0.17 mmol) in dimethylsulfoxide (1.2 mL) was stirred while heating at 110° C. in a microwave reactor for 20 minutes. After cooling to 25° C., the purple mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with an additional portion of ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered, concentrated under reduced pressure and purified by column chromatography on silica gel eluting with a step gradient (0-100%) of dichloromethane in hexanes to give the title compound as an off-white solid (34.0 mg, 63%). MS (ESI−) m/z 582 (M−H)−. 1H NMR (300 MHz, DMSO-d6) δ 1.05 (d, J=6.62 Hz, 6 H) 1.93 (m, 1 H) 2.73 (m, 2 H) 6.35 (m, 1 H) 7.19 (d, J=8.82 Hz, 1 H) 7.45 (m, 1 H) 7.61 (dd, J=8.82, 2.57 Hz, 1 H) 7.77 (m, 2 H) 7.94 (m, 2 H) 8.13 (dd, J=8.82, 2.57 Hz, 1 H) 8.19 (m, 1 H) 8.31 (d, J=2.21 Hz, 1 H).

후처리

  1. temperatureAfter cooling to 25° C.
  2. customthe purple mixture was partitioned between ethyl acetate and water
  3. extractionThe aqueous layer was extracted with an additional portion of ethyl acetate
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. custompurified by column chromatography on silica gel eluting with a step gradient (0-100%) of dichloromethane in hexanes

출처 및 근거

ORD 기록
ord-812bdacee9ae42239752f50c23413a17
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07902203B2

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