Sodium hydride → 2-{[2-({5,7-Diethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl}oxy)ethyl](4-fluorophenyl)amino}ethan-1-ol

HRID 1752798Notes

Reaction equation

HRID 1752798 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]([CH2:12][CH2:13][OH:14])[CH2:9][CH2:10][OH:11])=[CH:4][CH:3]=1.[H-].[Na+].CS([C:21]1[N:33]=[C:24]2[N:25]=[C:26]([CH2:31][CH3:32])[CH:27]=[C:28]([CH2:29][CH3:30])[N:23]2[N:22]=1)(=O)=O>O1CCCC1>[CH2:31]([C:26]1[CH:27]=[C:28]([CH2:29][CH3:30])[N:23]2[N:22]=[C:21]([O:11][CH2:10][CH2:9][N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[CH2:12][CH2:13][OH:14])[N:33]=[C:24]2[N:25]=1)[CH3:32]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 184230372-[(4-Fluorophenyl)(2-hydroxyethyl)amino]ethan-1-olHCID 867193202-Methanesulfonyl-5,7-diethyl-[1,2,4]triazolo[1,5-a]pyrimidine

Product 1

HCID 766846902-{[2-({5,7-Diethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl}oxy)ethyl](4-fluorophenyl)amino}ethan-1-olYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-[(4-fluorophenyl)(2-hydroxyethyl)amino]ethan-1-ol (200 mg, 1.01 mmol) and tetrahydrofuran (5 mL) was added to a 50 mL RBF under a nitrogen atmosphere with a magnetic stirring bar. The flask was cooled in an ice bath. Sodium hydride (60% dispersion in mineral oil) (40 mg, 1.01 mmol) was added (Effervescence). The reaction was warmed to room temperature and stirred for 10 minutes before 2-methanesulfonyl-5,7-diethyl-[1,2,4]-triazolo[1,5-a]pyrimidine (213 mg, 0.84 mmol) was added (Effervescence). Progress of the reaction was monitored by analytical HPLC with UV detection at 215 nm. The title compound eluted with a retention time of 4.1 min. After 90 minutes the reaction was concentrated then partitioned between dichloromethane (30 mL) and water (5 mL). The aqueous layer was extracted once more with dichloromethane (20 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated. The title crude material was purified by silica gel column chromatography using a gradient elution of 1-10% isopropanol in dichloromethane to afford the title compound as an oil that crystallized upon standing overnight (135 mg, 43% yield). 1H NMR (DMSO-d6, 400 MHz) δ ppm: 7.09 (s, 1H), 6.99 (t, 2H), 6.78 (m, 2H), 4.69 (t, 1H), 4.48 (t, 2H), 3.77 (t, 2H), 3.53 (q, 2H), 3.43 (t, 2H), 3.01 (q, 2H), 2.82 (q, 2H), 1.32 (t, 3H), 1.26 (t, 3H). EM (calc.): 373.2; MS (ESI) m/e: 374.3 (M+H)+.

Workup

  1. additionwas added to a 50 mL RBF under a nitrogen atmosphere with a magnetic stirring bar
  2. temperatureThe flask was cooled in an ice bath
  3. additionwas added (Effervescence)
  4. washThe title compound eluted with a retention time of 4.1 min
  5. concentrationAfter 90 minutes the reaction was concentrated
  6. customthen partitioned between dichloromethane (30 mL) and water (5 mL)
  7. extractionThe aqueous layer was extracted once more with dichloromethane (20 mL)
  8. dry with materialThe combined organic layers were dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe title crude material was purified by silica gel column chromatography
  12. washa gradient elution of 1-10% isopropanol in dichloromethane

Sources & evidence

ORD record
ord-af8b98a055304201a2459fb011c5fa3e
Source dataset
uspto-grants-2015_10
Patent number
US09163027B2

Reaction notes

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