Hydrochloric Acid → HCID 69672515, compound

HRID 1426344Notes

Reaction equation

HRID 1426344 reaction equation
[NH2:1][C:2]([C:4]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[N:7]=[C:6]([O:14][CH:15]2[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]2)[CH:5]=1)=[O:3].O1CCOCC1.Cl.[OH-].[NH4+]>C(#N)C>[NH:18]1[CH2:19][CH2:20][CH:15]([O:14][C:6]2[CH:5]=[C:4]([CH:9]=[C:8]([C:10]([F:12])([F:11])[F:13])[N:7]=2)[C:2]([NH2:1])=[O:3])[CH2:16][CH2:17]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14923Ammonium HydroxideHCID 312751,4-Dioxane2×HCID 86666505HCID 86666505, compound

Product 1

HCID 69672515HCID 69672515, compoundYield 60.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

tert-Butyl 4-{[4-(aminocarbonyl)-6-(trifluoromethyl)pyridin-2-yl]oxy}piperidine-1-carboxylate (0.20 g, 0.41 mmol, from Step B) was dissolved in 1,4-dioxane (3.0 mL, 38 mmol) and treated with 4.0M hydrogen chloride in dioxane (2.4 mL, 9.8 mmol). After 2.5 hours, the mixture was treated with ammonium hydroxide to achieve pH 11, and 15 mL of acetonitrile was added. The mixture was filtered and purified via preparative HPLC-MS (C18 eluting with a gradient of MeCN/H2O containing 0.15% NH4OH) to afford product (72 mg, 60%). 1H NMR (400 MHz, dmso) δ 8.35 (s, 1H), 7.91 (s, 1H), 7.76 (d, J=1.2 Hz, 1H), 7.49 (s, 1H), 5.05 (tt, J=8.9, 4.1 Hz, 1H), 2.95 (dt, J=12.6, 4.2 Hz, 2H), 2.57 (ddd, J=12.7, 10.0, 2.9 Hz, 2H), 2.01-1.87 (m, 2H), 1.60-1.41 (m, 2H); 19F NMR (376 MHz, dmso) δ−67.49 (s); LCMS (M+H)+: 290.1.

Workup

  1. additionwas added
  2. filtrationThe mixture was filtered
  3. custompurified via preparative HPLC-MS (C18
  4. washeluting with a gradient of MeCN/H2O containing 0.15% NH4OH)

Sources & evidence

ORD record
ord-5c65ceff33c54017a2dd43bed23bfdd3
Source dataset
uspto-grants-2015_01
Patent number
US08933085B2

Reaction notes

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