Water → HCID 86696368, compound

HRID 870668Notes

Reaction equation

HRID 870668 reaction equation
C[Al].[CH2:3]([NH2:6])[CH2:4][NH2:5].[CH2:7]([NH:11][C:12]1[CH:13]=[CH:14][C:15]2[N:16]([C:18]([C:21]3[CH:30]=[CH:29][C:24]([C:25]([O:27]C)=[O:26])=[CH:23][CH:22]=3)=[CH:19][N:20]=2)[N:17]=1)[CH2:8][CH2:9][CH3:10].O>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl.CO>[C:25]([OH:27])(=[O:26])[CH3:24].[NH2:5][CH2:4][CH2:3][NH:6][C:25](=[O:26])[C:24]1[CH:23]=[CH:22][C:21]([C:18]2[N:16]3[N:17]=[C:12]([NH:11][CH2:7][CH2:8][CH2:9][CH3:10])[CH:13]=[CH:14][C:15]3=[N:20][CH:19]=2)=[CH:30][CH:29]=1

Participants

8

Reactant 4

HCID 962WaterHCID 3301EthylenediamineHCID 16685210PUBCHEM_16685210HCID 86696367HCID 86696367, compound

Product 1

HCID 86696368HCID 86696368, compoundYield 7.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolvent2×HCID 6212ChloroformSolvent

Conditions

Temperature
110 °C

Procedure

The solution of methyl aluminum (2.0 M in hexane, 0.31 mL, 0.62 mmol) in toluene (2 mL) was cooled to 0° C. Then to the stirring solution was respectively added dropwise ethane-1,2-diamine (37.4 mg, 0.62 mmol), and the solution of methyl 4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)benzoate (126 mg, 0.39 mmol) in toluene (1 mL). The resulting reaction was refluxed at 110° C. overnight, and then cooled to 0° C. To the solution was added dropwise water (0.05 mL), methanol (0.2 mL) and chloroform (0.2 mL). The resulting mixture was refluxed on a steam bath for 15 m, and then filtered over sodium sulfate and concentrated. The residue was purified by preparative HPLC to afford N-(2-aminoethyl)-4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)benzamide acetic acid salt (5.7 mg, 4% yield) as a yellow solid: 1H NMR (METHANOL-d4) δ: 8.27-8.43 (m, J=8.6 Hz, 2H), 7.95-8.04 (m, J=8.3 Hz, 2H), 7.89 (s, 1H), 7.65 (d, J=9.6 Hz, 1H), 6.75 (d, J=9.9 Hz, 1H), 3.68 (t, J=5.9 Hz, 2H), 3.41 (t, J=7.2 Hz, 2H), 3.16 (br. s., 2H), 1.95 (br. s., 5H), 1.73 (t, J=7.1 Hz, 2H), 1.42-1.61 (m, 2H), 1.02 (t, J=7.3 Hz, 3H); LRMS (ESI) m/e 353.4 [(M+H)+, calcd for C19H25N6O 353.2].

Workup

  1. customThe resulting reaction
  2. temperaturecooled to 0° C
  3. temperatureThe resulting mixture was refluxed on a steam bath for 15 m
  4. filtrationfiltered over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-409caa088314409b9abf056d29544a02
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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