Hydrochloric Acid → HCID 178521274, compound

HRID 2401730Notes

Reaction equation

HRID 2401730 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:10]2[CH:14]=[C:13]([C:15]3[CH:20]=[CH:19][N:18]=[C:17](F)[CH:16]=3)[S:12][C:11]=2[C:22]2[N:26]=[CH:25][N:24](C3CCCCO3)[N:23]=2)[OH:9])=[CH:4][CH:3]=1.[CH2:33]([CH2:35][NH2:36])[OH:34].C(N(CC)C(C)C)(C)C.CS(C)=O.O1CCOCC1.Cl>O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:9])[C:10]2[CH:14]=[C:13]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([NH:36][CH2:35][CH2:33][OH:34])[CH:16]=3)[S:12][C:11]=2[C:22]2[NH:26][CH:25]=[N:24][N:23]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 679Dimethyl SulfoxideHCID 700EthanolamineHCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 68006689(4-chlorophenyl) {5-(2-fluoropyridin-4-yl)-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-3-thienyl}methanol

Product 1

HCID 178521274HCID 178521274, compoundYield 24.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
200 °C

Procedure

A mixture of (4-chlorophenyl){5-(2-fluoropyridin-4-yl)-2-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-3-thienyl}methanol (80.0 mg, 0.170 mmol), ethanolamine (0.104 g, 1.70 mmol) and N,N-diisopropylethylamine (0.118 mL, 0.679 mmol) in dimethylsulfoxide (0.5 mL, 7 mmol) was heated at 200° C. for 1 h under argon. The reaction mixture was cooled, diluted with water and extracted with butanol. The butanol layer was collected and evaporated to a residue which was purified by chromatography (SiO2, elution with 0-20% MeOH in DCM) to afford the intermediate. The intermediate in 1,4-dioxane (1.0 mL, 13 mmol) and conc HCl (1.0 mL, 12 mmol) was stirred at rt for 1 h. The solvent was evaporated and the residue was purified by chromatography (SiO2, elution with 0-70% (MeOH/DCM/NH4OH, 13/85/2) in DCM) to afford 2-({4-[4-[(4-chlorophenyl)(hydroxy)methyl]-5-(4H-1,2,4-triazol-3-yl)-2-thienyl]pyridin-2-yl}amino)ethanol (17.6 mg, 24.2%). LCMS: (AA) ES+ 428.2, 430.0; 1H NMR (400 MHz, d6-DMSO) δ: 14.66-14.13 (m, 1H), 8.68 (s, 1H), 7.94 (d, J=5.30 Hz, 1H), 7.58-7.48 (m, 3H), 7.38-7.30 (m, 2H), 6.81-6.68 (m, 3H), 6.60 (s, 1H), 4.72 (s, 1H), 3.57-3.45 (m, 2H), 3.34 (d, J=5.88 Hz, 3H).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted with butanol
  3. customThe butanol layer was collected
  4. customevaporated to a residue which
  5. customwas purified by chromatography (SiO2, elution with 0-20% MeOH in DCM)
  6. customto afford the intermediate
  7. customThe solvent was evaporated
  8. customthe residue was purified by chromatography (SiO2, elution with 0-70% (MeOH/DCM/NH4OH, 13/85/2) in DCM)

Sources & evidence

ORD record
ord-ccaf0518b40d441d8f3d4cd278e16aa1
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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