Hydrochloric Acid → 4-(6-Methoxypyrazolo[1,5-b]pyridazin-3-yl)-N-[4-(4-methyl-1-piperazinyl)phenyl]-2-pyrimidinamine

HRID 729346Notes

Reaction equation

CN(C)/[CH:3]=[CH:4]/[C:5]([C:7]1[CH:8]=[N:9][N:10]2[C:15]=1[CH:14]=[CH:13][C:12]([O:16][CH3:17])=[N:11]2)=O.[CH3:19][N:20]1[CH2:25][CH2:24][N:23]([C:26]2[CH:31]=[CH:30][C:29]([NH:32][C:33]([NH2:35])=[NH:34])=[CH:28][CH:27]=2)[CH2:22][CH2:21]1.Cl.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:17][O:16][C:12]1[CH:13]=[CH:14][C:15]2[N:10]([N:9]=[CH:8][C:7]=2[C:5]2[CH:4]=[CH:3][N:35]=[C:33]([NH:32][C:29]3[CH:28]=[CH:27][C:26]([N:23]4[CH2:24][CH2:25][N:20]([CH3:19])[CH2:21][CH2:22]4)=[CH:31][CH:30]=3)[N:34]=2)[N:11]=1

Participants

Conditions

Temperature: 130 °C

Procedure

To a solution (2E)-3-(dimethylamino)-1-(6-methoxypyrazolo[1,5-b]pyridazin-3-yl)-2-propen-1-one (40 mg, 0.16 mmol) in DMF (2.0 mL) was added N-[4-(4-methyl-1-piperazinyl)phenyl]guanidine.HCl (99 mg, 0.32 mmol) and potassium carbonate (112 mg, 0.80 mmol). The reaction was heated at an oil bath temperature of 130° C. for about 18 hours. The mixture was cooled to RT and the solvent was removed in vacuo. The residue was dissolved in chloroform and filtered. The filtrate was concentrated in vacuo then disolved in CH2Cl2 and triturated with diethylether to give the title compound as a yellow solid (12 mg, 18%). 1H-NMR (400 MHz, CDCl3) δ 8.67 (d, 1H, J=9.5 Hz), 8.35 (d, 1H, J=5.2 Hz), 8.29 (s, 1H), 7.46 (d, 2H, J=8.9 Hz), 6.98 (m, 3H), 6.90 (s, 1H), 6.75 (d, 1H, J=9.5 Hz), 4.09 (s, 3H), 3.23 (m, 4H), 2.64 (m, 4H), 2.39 (s, 3H); MS (ESI) (M+H)+ 417.

Workup

temperatureThe mixture was cooled to RT
customthe solvent was removed in vacuo
dissolutionThe residue was dissolved in chloroform
filtrationfiltered
concentrationThe filtrate was concentrated in vacuo
customtriturated with diethylether

Sources & evidence

ORD record: ord-eb392f7d3f86496fbaf55f50ac5e5d8b
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07582630B2

Reaction notes

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