Hydrochloric Acid → tert-butyl (5-(2-(4-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)-5-chlorophenyl)benzo[d]isoxazol-3-yl)carbamate

HRID 2203439노트

반응식

HRID 2203439 반응식
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:25][C:26]2[CH:31]=[C:30]([F:32])[C:29]([S:33](=[O:52])(=[O:51])[N:34](CC3C=CC(OC)=CC=3OC)[C:35]3[S:39][N:38]=[CH:37][N:36]=3)=[CH:28][C:27]=2[F:53])=[C:6]([C:8]2[CH:9]=[CH:10][C:11]3[O:15][N:14]=[C:13]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[C:12]=3[CH:24]=2)[CH:7]=1.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+].Cl>ClCCl>[S:39]1[C:35]([NH:34][S:33]([C:29]2[C:30]([F:32])=[CH:31][C:26]([O:25][C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][C:6]=3[C:8]3[CH:9]=[CH:10][C:11]4[O:15][N:14]=[C:13]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:21])([CH3:22])[CH3:20])[C:12]=4[CH:24]=3)=[C:27]([F:53])[CH:28]=2)(=[O:51])=[O:52])=[N:36][CH:37]=[N:38]1

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 71558770tert-butyl (5-(5-chloro-2-(4-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)phenyl)benzo[d]isoxazol-3-yl)carbamate

생성물 1

HCID 71558918tert-butyl (5-(2-(4-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)-5-chlorophenyl)benzo[d]isoxazol-3-yl)carbamate수율 59%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

반응 조건

온도
0 °C

실험 절차

To a solution of tert-butyl (5-(5-chloro-2-(4-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)phenyl)benzo[d]isoxazol-3-yl)carbamate (0.150 g, 0.19 mmol) in dichloromethane (2 mL) was added trifluoroacetic acid (0.1 mL) at 0° C. The reaction mixture was stirred for 20 minutes at 0° C. and saturated aqueous sodium bicarbonate (5 mL) was added. The mixture was allowed to warm to ambient temperature, diluted with dichloromethane (50 mL), and acidified to pH 5 with 1 N hydrochloric acid. The organic phase was washed with brine (10 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography, eluting with a 0-100% ethyl acetate in hexanes, followed by a 0-10% gradient of methanol in ethyl acetate, to afford tert-butyl (5-(2-(4-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)-5-chlorophenyl)benzo[d]isoxazol-3-yl)carbamate in 59% yield (0.071 g) as a colorless solid: 1H NMR (300 MHz, DMSO-d6) δ10.52 (s, 1H), 8.27 (s, 1H), 8.24 (d, J=1.5 Hz, 1H), 7.77 (dd, J=8.8, 1.6 Hz, 1H), 7.69 (d, J=8.7 Hz, 1H), 7.67 (dd, J=6.8, 3.3 Hz, 1H), 7.63 (d, J=2.5 Hz, 1H), 7.48 (dd, J=8.8, 2.6 Hz, 1H), 7.22 (d, J=8.9 Hz, 1H), 7.22-7.16 (m, 1H), 1.44 (s, 9H), (NH not observed); MS (ES+) m/z 657.6 (M+23), 659.5 (M+23).

후처리

  1. temperatureto warm to ambient temperature
  2. washThe organic phase was washed with brine (10 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography
  7. washeluting with a 0-100% ethyl acetate in hexanes

출처 및 근거

ORD 기록
ord-7fbb54ab1c254d238f2af8a797b66c21
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09365578B2

반응 노트

불러오는 중…