Pyridine → N-(6-(3-(Isoquinoline-5-sulfonamido)phenyl)imidazo[1,2-b]pyridazin-2-yl)acetamide

HRID 1162437Notes

Reaction equation

HRID 1162437 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]([CH:14]=[C:15]([NH:17][C:18](=[O:20])[CH3:19])[N:16]=3)[N:13]=2)[CH:5]=[CH:6][CH:7]=1.N1C=CC=CC=1.Cl.[CH:28]1[C:37]2[CH:36]=[CH:35][CH:34]=[C:33]([S:38](Cl)(=[O:40])=[O:39])[C:32]=2[CH:31]=[CH:30][N:29]=1>CN(C=O)C>[CH:28]1[C:37]2[CH:36]=[CH:35][CH:34]=[C:33]([S:38]([NH:1][C:2]3[CH:3]=[C:4]([C:8]4[CH:9]=[CH:10][C:11]5[N:12]([CH:14]=[C:15]([NH:17][C:18](=[O:20])[CH3:19])[N:16]=5)[N:13]=4)[CH:5]=[CH:6][CH:7]=3)(=[O:40])=[O:39])[C:32]=2[CH:31]=[CH:30][N:29]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 13116932Isoquinoline-5-sulfonyl chloride hydrochlorideHCID 57749413N-(6-(3-Aminophenyl)imidazo[1,2-b]pyridazin-2-yl)acetamide

Product 1

HCID 44124634N-(6-(3-(Isoquinoline-5-sulfonamido)phenyl)imidazo[1,2-b]pyridazin-2-yl)acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a 10-mL, round-bottomed flask was added N-(6-(3-aminophenyl)imidazo[1,2-b]pyridazin-2-yl)acetamide (Example 5) (0.032 g, 0.12 mmol), DMF (2.0 mL), pyridine (0.015 mL, 0.180 mmol), and isoquinoline-5-sulfonyl chloride hydrochloride (0.0395 g, 0.150 mmol, Toronto Research Chemicals, Ottawa, Ontario). The mixture was stirred at 25° C. for 5 h then concentrated under reduced pressure. The residue was purified by preparative HPLC (Phenomenex Synergi 4μ MAX-RP 150×21.2 mm, 2 to 100% CH3CN/H2O, 0.1% TFA, over 15 min) (Phenomenex, Torrance, Calif.) to afford the title compound as a light-yellow solid. MS (ESI positive ion) m/z: 459 (M+1). 1H NMR (400 MHz, DMSO-d6): δ ppm 11.03 (s, 1H), 10.91 (s, 1H), 9.50 (s, 1H), 8.75 (d, J=6.5 Hz, 1H), 8.58 (d, J=6.0 Hz, 1H), 8.53 (d, J=7.0 Hz, 1H), 8.45 (d, J=8.0 Hz, 1H), 8.25 (s, 1H), 8.02 (d, J=9.5 Hz, 1H), 7.84 (t, J=7.8 Hz, 1H), 7.71 (s, 1H), 7.62 (d, J=7.5 Hz, 1H), 7.56 (d, J=9.5 Hz, 1H), 7.34 (t, J=7.8 Hz, 1H), 7.16 (d, J=8.0 Hz, 1H), 2.11 (s, 3H).

Workup

  1. concentrationthen concentrated under reduced pressure
  2. customThe residue was purified by preparative HPLC (Phenomenex Synergi 4μ MAX-RP 150×21.2 mm, 2 to 100% CH3CN/H2O, 0.1% TFA, over 15 min) (Phenomenex, Torrance, Calif.)

Sources & evidence

ORD record
ord-b428067117964991b8e33fd395fb2f0c
Source dataset
uspto-grants-2010_10
Patent number
US07820665B2

Reaction notes

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