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

HRID 718579Notes

Reaction equation

HRID 718579 reaction equation
[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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-eca9fddd513c4d499d5fd4a61e153d05
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

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