Dimethylamine → HCID 67048044, compound

HRID 606912Notes

Reaction equation

HRID 606912 reaction equation
Cl[CH2:2][C:3]1[CH:4]=[C:5]([C:10]#[C:11][C:12]2[CH:13]=[N:14][CH:15]=[C:16]([CH:19]=2)[C:17]#[N:18])[CH:6]=[CH:7][C:8]=1[F:9].[CH3:20][NH:21][CH3:22]>O1CCCC1.C(OCC)(=O)C.C(OCC)C>[CH3:20][N:21]([CH2:2][C:3]1[CH:4]=[C:5]([C:10]#[C:11][C:12]2[CH:13]=[N:14][CH:15]=[C:16]([CH:19]=2)[C:17]#[N:18])[CH:6]=[CH:7][C:8]=1[F:9])[CH3:22]

Participants

6

Reactant 2

HCID 674DimethylamineHCID 67047920HCID 67047920, compound

Product 1

HCID 67048044HCID 67048044, compoundYield 58%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Treat 5-(3-chloromethyl-4-fluorophenylethynyl)-nicotinonitrile, (prepared as described in PREPARATION 32), (100 mg, 0.37 mmol) with a 2.0 M solution of dimethylamine in tetrahydrofuran (3 mL) and heat at 70° C. in a sealed tube for 2 h. Cool to room temperature, dilute with ethyl acetate, and wash with an aqueous saturated solution of sodium bicarbonate and an aqueous saturated solution of sodium chloride. Dry (sodium sulfate), filter, and concentrate. Purify by silica gel chromatography, eluting with a gradient from 50:50 hexanes:dichloromethane to 90:10 (50:50 hexanes:dichloromethane):methanol, to give a yellow oil. Dissolve the oil in diethyl ether and extract twice with 1 N hydrochloric acid. Combine the aqueous layers and make basic with a 1 N sodium hydroxide. Extract the resultant purple aqueous layer three times with ethyl acetate. Combine the organic extracts, wash with an aqueous saturated solution of sodium chloride, dry (sodium sulfate), filter, and concentrate to an oil. Concentration of the oil from diethyl ether provides the title compound as a crystalline solid (60 mg, 58%).

Workup

  1. temperatureCool to room temperature
  2. washwash with an aqueous saturated solution of sodium bicarbonate
  3. dry with materialDry (sodium sulfate)
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify by silica gel chromatography
  7. washeluting with a gradient from 50:50 hexanes
  8. customdichloromethane to 90:10 (50:50 hexanes:dichloromethane):methanol, to give a yellow oil
  9. extractionextract twice with 1 N hydrochloric acid
  10. extractionExtract the resultant purple aqueous layer three times with ethyl acetate
  11. washwash with an aqueous saturated solution of sodium chloride
  12. dry with materialdry (sodium sulfate)
  13. filtrationfilter
  14. concentrationconcentrate to an oil

Sources & evidence

ORD record
ord-09f80bb53f2c4c56aa00f9521ee7b09e
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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