Propanenitrile, 3-(methylamino)- → 5-(3-{[(2-Cyanoethyl)methylamino]methyl}-4-fluorophenylethynyl)-nicotinonitrile

HRID 606916Notes

Reaction equation

HRID 606916 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[CH:11]=[N:12][CH:13]=[C:14]([CH:17]=2)[C:15]#[N:16])=[CH:4][C:3]=1[CH:18]=O.[CH3:20][NH:21][CH2:22][CH2:23][C:24]#[N:25].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClC(Cl)C>[C:24]([CH2:23][CH2:22][N:21]([CH2:18][C:3]1[CH:4]=[C:5]([C:8]#[C:9][C:10]2[CH:11]=[N:12][CH:13]=[C:14]([CH:17]=2)[C:15]#[N:16])[CH:6]=[CH:7][C:2]=1[F:1])[CH3:20])#[N:25]

Participants

5

Reactant 3

HCID 69656Propanenitrile, 3-(methylamino)-HCID 5049666Sodium triacetoxyborohydrideHCID 848197895-((4-Fluoro-3-formylphenyl)ethynyl)nicotinonitrile

Product 1

HCID 670482505-(3-{[(2-Cyanoethyl)methylamino]methyl}-4-fluorophenylethynyl)-nicotinonitrileYield 43%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

Dissolve 5-(4-fluoro-3-formylphenylethynyl)nicotinonitrile, (prepared as described in PREPARATION 38) (100 mg, 0.40 mmol) in dichloroethane (2 mL) and treat with N-methyl-β-alaninenitrile (0.041 mL, 0.44 mmol) and sodium triacetoxyborohydride (110 mg, 0.52 mmol). After stirring for 5.5 h, quench with water (2 mL), dilute with dichloromethane and extract three times with 0.5 N hydrochloric acid, but thin layer chromatography shows some product still remaining in the organic phase. Add 1 N sodium hydroxide to the aqueous layer until it is basic then extract twice with ethyl acetate. Combine the dichloromethane layer with the ethyl acetate extracts and wash with an aqueous saturated solution of sodium chloride, dry (sodium sulfate), filter, and concentrate. Purify by silica gel chromatography, eluting with 90:10 to 80:20 dichloromethane:ethyl acetate, to give the title compound as a white crystalline solid (55 mg, 43%).

Workup

  1. dissolutionDissolve
  2. customquench with water (2 mL)
  3. additiondilute with dichloromethane
  4. extractionextract three times with 0.5 N hydrochloric acid, but thin layer chromatography
  5. additionAdd 1 N sodium hydroxide to the aqueous layer until it
  6. extractionis basic then extract twice with ethyl acetate
  7. washwash with an aqueous saturated solution of sodium chloride
  8. dry with materialdry (sodium sulfate)
  9. filtrationfilter
  10. concentrationconcentrate
  11. customPurify by silica gel chromatography
  12. washeluting with 90:10 to 80:20 dichloromethane

Sources & evidence

ORD record
ord-213e0b1ce0c842d895a216237d97c343
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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