Hydrochloric Acid → 2-([1,2,4]Triazolo[4,3-a]pyridin-3-yl)-8-((trans)-3-fluoropiperidin-4-yloxy)quinoline

HRID 876488Notes

Reaction equation

[N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([O:20][C@@H:21]4[CH2:26][CH2:25][N:24](C(OCC5C=CC=CC=5)=O)[CH2:23][C@H:22]4[F:37])[CH:14]=[CH:15][CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.Cl.C([O-])(O)=O.[Na+].[Na+].[Cl-]>O1CCOCC1.O>[N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([O:20][C@@H:21]4[CH2:26][CH2:25][NH:24][CH2:23][C@H:22]4[F:37])[CH:14]=[CH:15][CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12

Participants

Conditions

Temperature: 100 °C

Procedure

Non-racemic (trans)-benzyl 4-(2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)-3-fluoropiperidine-1-carboxylate (0.304 g, 0.611 mmol) was dissolved in dioxane (7.6 mL) and treated with 6 M hydrogen chloride (7.64 mL, 45.8 mmol), and the reaction mixture was heated at 100° C. for 15 hours. The reaction was cooled and carefully neutralized with solid NaHCO3. Additional water was added to dissolve the resulting NaCl as the neutralization proceeded. The resulting aqueous layer (pH 8-9) was extracted with methylene chloride and the combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude product was chromatographed on SiO2 eluting with a gradient of 2% NH4OH in isopropanol/methylene chloride. The desired product was isolated as a white foam (62.6 mg). MS APCI (+) m/z 364.2 (M+1) detected.

Workup

temperatureThe reaction was cooled
extractionThe resulting aqueous layer (pH 8-9) was extracted with methylene chloride
dry with materialthe combined organic layers were dried over Na2SO4
concentrationconcentrated in vacuo
customThe crude product was chromatographed on SiO2 eluting with a gradient of 2% NH4OH in isopropanol/methylene chloride

Sources & evidence

ORD record: ord-35fe6c15e0a94832b9b6d32a3753f138
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987251B2

Reaction notes

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