Hydrochloric Acid → HCID 44434935, compound

HRID 130813Notes

Reaction equation

HRID 130813 reaction equation
[CH2:1]([NH:8][CH2:9][CH2:10][C:11]1[CH:25]=[CH:24][C:14]([O:15][C:16]2[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][N:17]=2)=[CH:13][CH:12]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CSC.B.Cl.[OH-].[Na+]>C1COCC1>[NH2:21][CH2:20][C:19]1[CH:22]=[CH:23][C:16]([O:15][C:14]2[CH:24]=[CH:25][C:11]([CH2:10][CH2:9][NH:8][CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)=[CH:12][CH:13]=2)=[N:17][CH:18]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 12423031(Dimethyl sulfide)trihydroboronHCID 44434934HCID 44434934, compound

Product 1

HCID 44434935HCID 44434935, compoundYield 21.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

Dissolve 6-[4-(2-benzylaminoethyl)phenoxy]nicotinonitrile 0.0650 g, 0.197 mmol) in THF (2.0 mL). Heat to 65° C. before adding borane-dimethyl sulfide (0.021 mL, 0.217 mmol). Continue heating for about 2 hours. Then add 5.0 N HCl (0.30 mL). Heat at reflux for 1 hour 20 minutes before cooling to room temperature. Add 1.0 N NaOH until the solution is basic. Extract with ether (3×25 mL). Concentrate the organic layer before purifying by flash chromatography, eluting with 10% (2.0 M NH3 in methanol), 10% methanol and 80% ethyl acetate. Load the product onto a 1 g SCX column with methanol. Wash with methanol and elute with 2.0 M NH3 in methanol. Run a second flash 40 column eluting with 10% (2.0 M NH3 in methanol), 5% methanol and 85% ethyl acetate. Load the product onto a 5 g SCX column with methanol. Wash the column with methanol (4×10 mL) and 25% (2.0 M NH3 in methanol) in methanol (1×10 mL). Then elute with 50% (2.0 M NH3 in methanol) in methanol to give the title compound (0.0141 g, 21.7%): MS ES+ 334.0 (M+H)+, base peak ES+ 227.0 (M−NHCH2C6H5)+; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), acetonitrile in water containing 0.01% concentrated HCl at 1.0 mL/min, 30-99% over 19 min], tR=4.8 min, 91.2% purity.

Workup

  1. temperatureContinue heating for about 2 hours
  2. temperatureHeat
  3. temperatureat reflux for 1 hour 20 minutes
  4. temperaturebefore cooling to room temperature
  5. extractionExtract with ether (3×25 mL)
  6. concentrationConcentrate the organic layer
  7. custombefore purifying by flash chromatography
  8. washeluting with 10% (2.0 M NH3 in methanol), 10% methanol and 80% ethyl acetate
  9. washWash with methanol
  10. washelute with 2.0 M NH3 in methanol
  11. washeluting with 10% (2.0 M NH3 in methanol), 5% methanol and 85% ethyl acetate
  12. washWash the column with methanol (4×10 mL) and 25% (2.0 M NH3 in methanol) in methanol (1×10 mL)
  13. washThen elute with 50% (2.0 M NH3 in methanol) in methanol

Sources & evidence

ORD record
ord-6aef33c0c55d4490bcfd859fc7d2334b
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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