Trifluoroacetic acid methylene chloride → Trifluoroacetic acid
Reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:18]2[CH:19]=[CH:20][C:21]3[N:22]([C:24]([S:27][C:28]4[CH:29]=[CH:30][C:31]5[N:32]([CH:34]=[C:35]([NH:37][C:38]([CH:40]6[CH2:42][CH2:41]6)=[O:39])[N:36]=5)[N:33]=4)=[N:25][N:26]=3)[CH:23]=2)[CH:6]=[N:7][C:8]=1[O:9]COCC[Si](C)(C)C)#[N:2].[C:43]([OH:49])([C:45]([F:48])([F:47])[F:46])=[O:44].C(Cl)Cl>>[C:1]([C:3]1[CH:4]=[C:5]([C:18]2[CH:19]=[CH:20][C:21]3[N:22]([C:24]([S:27][C:28]4[CH:29]=[CH:30][C:31]5[N:32]([CH:34]=[C:35]([NH:37][C:38]([CH:40]6[CH2:42][CH2:41]6)=[O:39])[N:36]=5)[N:33]=4)=[N:25][N:26]=3)[CH:23]=2)[CH:6]=[N:7][C:8]=1[OH:9])#[N:2].[C:43]([OH:49])([C:45]([F:48])([F:47])[F:46])=[O:44]Participants
Procedure
As a crude reaction mixture, N-(6-(6-(5-cyano-6-((2-(trimethylsilyl)ethoxy)methoxy)pyridin-3-yl)-[1,2,4]triazolo[4,3-a]-pyridin-3-ylthio)imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide was refluxed in TFA:DCM (1:1, 5 mL) for 30 min. The reaction was then concentrated and purified by preparative LCMS to provide the title compound, N-(6-(6-(5-cyano-6-hydroxypyridin-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-ylthio)imidazo[1,2-b]pyridazin-2-yl)cyclopropanecarboxamide as a TFA salt. The product was then dissolved in MeOH, treated 4M HCl in dioxane, and concentrated to dryness to provide the HCl salt of the title compound. 1H NMR (METHANOL-d4, 400 MHz): δ=8.80 (br. s., 1 H), 8.51 (d, J=2.5 Hz, 1 H), 8.13 (d, J=2.8 Hz, 1 H), 8.04 (d, J=9.6 Hz, 1 H), 7.79-7.96 (m, 3 H), 7.27 (d, J=7.8 Hz, 1 H), 1.83 (br. s., 1 H), 0.91 ppm (d, J=16.7 Hz, 4 H). ESI-MS:m/z 513.4 (M+H)+.
Workup
- concentrationThe reaction was then concentrated
- custompurified by preparative LCMS
Sources & evidence
- ORD record
- ord-1b953a8ed74f492699d6ba93a723d12d
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08178534B2
Reaction notes
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