Hydrochloric Acid → HCID 136325905, compound

HRID 718179Notes

Reaction equation

HRID 718179 reaction equation
[C:1]([C:5]1[NH:9][C:8](=[O:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][N:21]=[C:20]([C:24]4[CH:25]=[N:26][N:27]([CH2:29][CH2:30][O:31]C5CCCCO5)[CH:28]=4)[CH:19]=3)=[C:13]([CH3:38])[N:12]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.C([O-])(O)=O.[Na+]>CC#N.O>[C:1]([C:5]1[NH:9][C:8](=[O:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]3[CH:23]=[CH:22][N:21]=[C:20]([C:24]4[CH:25]=[N:26][N:27]([CH2:29][CH2:30][OH:31])[CH:28]=4)[CH:19]=3)=[C:13]([CH3:38])[N:12]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 136930525HCID 136930525, compound

Product 1

HCID 136325905HCID 136325905, compoundYield 87.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Procedure

3-(tert-Butyl)-1-(6-methyl-5-((2-(1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-1H-1,2,4-triazol-5(4H)-one (0.18 g, 0.34 mmol) was dissolved in MeCN and treated with a HCl (4 M in dioxane) (0.25 mL, 1.0 mmol). The mixture was stirred at RT for 20 min. Sat. NaHCO3 (aq) (15 mL) was added and the suspension was extracted with EtOAc (5×15 mL). The combined organics were dried (Na2SO4) and concentrated in vacuo. The residue was purified by silica gel chromatography (MeOH/DCM). The product was triturated with MeCN (5 mL) and sonicated for 5 min. The solid was isolated by filtration, redissolved in MeCN and water, frozen to −78° C., and lyophilized to afford 3-(tert-butyl)-1-(5-((2-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)pyridin-4-yl)oxy)-6-methylpyridin-2-yl)-1H-1,2,4-triazol-5(4H)-one (0.13 g, 82%) as an off white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.97 (s, 1H), 8.37 (d, J=5.7 Hz, 1H), 8.27 (s, 1H), 7.99 (s, 1H), 7.85 (d, J=8.8 Hz, 1H), 7.68 (d, J=8.8 Hz, 1H), 7.21 (d, J=2.4 Hz, 1H), 6.64 (dd, J=5.7, 2.4 Hz, 1H), 4.89 (t, J=5.3 Hz, 1H), 4.13 (t, J=5.6 Hz, 2H), 3.73 (q, J=5.5 Hz, 2H), 2.33 (s, 3H), 1.27 (s, 9H); MS (ESI) m/z: 436.2 (M+H+).

Workup

  1. extractionthe suspension was extracted with EtOAc (5×15 mL)
  2. dry with materialThe combined organics were dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by silica gel chromatography (MeOH/DCM)
  5. customThe product was triturated with MeCN (5 mL)
  6. customsonicated for 5 min
  7. customThe solid was isolated by filtration

Sources & evidence

ORD record
ord-3ae6918720004d51a64a523178a2fc63
Source dataset
uspto-grants-2015_11
Patent number
US09193719B2

Reaction notes

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