Sodium Hydroxide → 8-((6-Phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylamino)-1,5-naphthyridin-3-ol

HRID 40194

Reaction equation

C[O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([NH:13][CH2:14][C:15]3[N:19]4[N:20]=[C:21]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[CH:22]=[CH:23][C:18]4=[N:17][N:16]=3)=[CH:8][CH:9]=[N:10]2)=[N:5][CH:4]=1.[OH-].[Na+]>Br.C(Cl)Cl.O>[C:24]1([C:21]2[CH:22]=[CH:23][C:18]3[N:19]([C:15]([CH2:14][NH:13][C:7]4[CH:8]=[CH:9][N:10]=[C:11]5[C:6]=4[N:5]=[CH:4][C:3]([OH:2])=[CH:12]5)=[N:16][N:17]=3)[N:20]=2)[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

Conditions

Temperature: 100 °C

Procedure

In a 25 mL sealed tube was dissolved 7-methoxy-N-((6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methyl)-1,5-naphthyridin-4-amine (prepared according to General Method D) (300 mg, 782 μmol) in 5 mL of concentrated HBr then stirred and heated at 100° C. for 48 h. The reaction mixture was diluted with DCM and H2O then neutralized with NaOH (1N) to neutral pH. The aqueous phase was extracted 3× with DCM then the organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude mixture was purified by MPLC (ISCO) with DCM:MeOH:NH4OH (90:10:1) and then triturated with hot EtOH to afforded 8-((6-phenyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methylamino)-1,5-naphthyridin-3-ol (230 mg, 79.6% yield) as a tan solid. MS m/z=369.1 [M+1]+. Calc'd for C20H15N7O: 370.0.

Workup

customIn a 25 mL sealed tube
extractionThe aqueous phase was extracted 3× with DCM
dry with materialthe organic layer was dried over Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe crude mixture was purified by MPLC (ISCO) with DCM:MeOH:NH4OH (90:10:1)
customtriturated with hot EtOH

Sources & evidence

ORD record: ord-b9d493f86bcc489bb27580e06a09dbe6
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08524900B2

Linked notes

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