1,3-Propanediamine → HCID 86696379, compound

HRID 870678Notes

Reaction equation

HRID 870678 reaction equation
C[Al].[CH2:3]([NH2:7])[CH2:4][CH2:5][NH2:6].[CH2:8]([NH:12][C:13]1[CH:14]=[CH:15][C:16]2[N:17]([C:19]([C:22]3[CH:31]=[CH:30][C:25]([C:26]([O:28]C)=[O:27])=[CH:24][CH:23]=3)=[CH:20][N:21]=2)[N:18]=1)[CH2:9][CH2:10][CH3:11].O>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl.CO>[C:26]([OH:28])(=[O:27])[CH3:25].[CH2:8]([NH:12][C:13]1[CH:14]=[CH:15][C:16]2[N:17]([C:19]([C:22]3[CH:23]=[CH:24][C:25]([C:26]4[NH:6][CH2:5][CH2:4][CH2:3][N:7]=4)=[CH:30][CH:31]=3)=[CH:20][N:21]=2)[N:18]=1)[CH2:9][CH2:10][CH3:11]

Participants

8

Reactant 4

HCID 4281,3-PropanediamineHCID 962WaterHCID 16685210PUBCHEM_16685210HCID 86696367HCID 86696367, compound

Product 1

HCID 86696379HCID 86696379, compoundYield 28.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolvent2×HCID 6212ChloroformSolvent

Conditions

Temperature
110 °C

Procedure

The solution of methyl aluminum (2.0 M in hexane, 0.32 mL, 0.64 mmol) in toluene (2 mL) was cooled to 0° C. Then to the stirring solution was respectively added dropwise propane-1,3-diamine (48 mg, 0.64 mmol), and the solution of methyl 4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)benzoate (130 mg, 0.4 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-butyl-3-(4-(1,4,5,6-tetrahydropyrimidin-2-yl)phenyl)imidazo[1,2-b]pyridazin-6-amine acetic acid salt (23.3 mg, 17% yield) as a white solid: 1H NMR (METHANOL-d4) δ: 8.42-8.56 (m, J=8.6 Hz, 2H), 7.96 (s, 1H), 7.75-7.86 (m, J=8.6 Hz, 2H), 7.66 (d, J=9.6 Hz, 1H), 6.78 (d, J=9.9 Hz, 1H), 3.64 (t, J=5.8 Hz, 4H), 3.41 (t, J=7.1 Hz, 2H), 2.16 (t, J=5.7 Hz, 2H), 1.94 (s, 5H), 1.73 (t, J=7.2 Hz, 2H), 1.42-1.58 (m, 2H), 1.02 (t, J=7.3 Hz, 3H); LRMS (ESI) m/e 349.5 [(M+H)+, calcd for C20H24N6 349.2].

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-9726a21721f741f490e1a0d9662b155b
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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