Diisopropylethylamine → (E)-N-((4-(8-Morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[1,2-b]pyridazin-3-yl)phenyl)carbamoyl)methanesulfonamide

HRID 718579노트

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HRID 718579 반응식
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]3[N:9]([C:13]([C:28]4[CH:34]=[CH:33][C:31]([NH2:32])=[CH:30][CH:29]=4)=[C:14](/[CH:16]=[CH:17]/[C:18]4[CH:27]=[CH:26][C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[N:19]=4)[N:15]=3)[N:10]=[CH:11][CH:12]=2)[CH2:3][CH2:2]1.[CH3:35][S:36]([NH:39][C:40](=O)[O:41]CC)(=[O:38])=[O:37].CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[O:1]1[CH2:2][CH2:3][N:4]([C:7]2[C:8]3[N:9]([C:13]([C:28]4[CH:29]=[CH:30][C:31]([NH:32][C:40]([NH:39][S:36]([CH3:35])(=[O:38])=[O:37])=[O:41])=[CH:33][CH:34]=4)=[C:14](/[CH:16]=[CH:17]/[C:18]4[CH:27]=[CH:26][C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[N:19]=4)[N:15]=3)[N:10]=[CH:11][CH:12]=2)[CH2:5][CH2:6]1

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 1201508(Methylsulfonyl)-carbamic acid ethyl esterHCID 117728645(E)-4-(8-Morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[1,2-b]pyridazin-3-yl)aniline

생성물 1

HCID 117728379(E)-N-((4-(8-Morpholino-2-(2-(quinolin-2-yl)vinyl)imidazo[1,2-b]pyridazin-3-yl)phenyl)carbamoyl)methanesulfonamide

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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온도
100 °C

실험 절차

To a mixture of compound 10b (82 mg, 0.18 mmol) and compound 12a (0.14 g, 0.86 mmol) in DMF (2 mL) was added DIEA (0.16 mL, 0.91 mmol). The mixture was stirred at 100° C. for 2 h. The solution was cooled down, and diluted with DCM (10 mL). The organic layer was washed with 1 N HCl solution (10 mL) and brine, dried over MgSO4, filtered and concentrated. The resulting residue was purified by flash column chromatography on silica gel (0-10% CH3OH/DCM) to give the title compound 50 as a red solid. 1H-NMR (400 MHz, DMSO-d6) δ (ppm): 8.96 (s, 1H), 8.31 (d, J=8.6 Hz, 1H), 8.12 (d, J=5.6 Hz, 1H), 7.94 (dd, J=13.6, 8.2 Hz, 2H), 7.83 (d, J=8.6 Hz, 1H), 7.66-7.77 (m, 5H), 7.57-7.63 (m, 2H), 7.51-7.57 (m, 1H), 6.40 (d, J=5.9 Hz, 1H), 4.03-4.14 (m, 4H), 3.83-3.92 (m, 4H), 3.17 (s, 3H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C29H27N7O4S: 570.2 (M+H). Found 570.4.

후처리

  1. temperatureThe solution was cooled down
  2. washThe organic layer was washed with 1 N HCl solution (10 mL) and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting residue was purified by flash column chromatography on silica gel (0-10% CH3OH/DCM)

출처 및 근거

ORD 기록
ord-eca9fddd513c4d499d5fd4a61e153d05
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09193736B2

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