3-Amino-4,4-difluorobut-2-enenitrile → N-{2-[3,5-Dicyano-2,6-bis(difluoromethyl)-1,4-dihydropyridin-4-yl]furo[3,2-c]pyridin-4-yl}benzamide

HRID 1910669Notes

Reaction equation

HRID 1910669 reaction equation
[CH:1]([C:3]1[O:11][C:10]2[CH:9]=[CH:8][N:7]=[C:6]([NH:12][C:13](=[O:20])[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:5]=2[CH:4]=1)=O.[NH2:21][C:22]([CH:26]([F:28])[F:27])=[CH:23][C:24]#[N:25]>C(O)(=O)C.C(O)CCC>[C:24]([C:23]1[CH:1]([C:3]2[O:11][C:10]3[CH:9]=[CH:8][N:7]=[C:6]([NH:12][C:13](=[O:20])[C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=4)[C:5]=3[CH:4]=2)[C:23]([C:24]#[N:25])=[C:22]([CH:26]([F:28])[F:27])[NH:21][C:22]=1[CH:26]([F:28])[F:27])#[N:25]

Participants

5

Reactant 2

HCID 762236343-Amino-4,4-difluorobut-2-enenitrileHCID 86685438N-(2-Formylfuro[3,2-c]pyridin-4-yl)benzamide

Product 1

HCID 52938931N-{2-[3,5-Dicyano-2,6-bis(difluoromethyl)-1,4-dihydropyridin-4-yl]furo[3,2-c]pyridin-4-yl}benzamide

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 2631-ButanolSolvent

Procedure

A solution of 200 mg (0.75 mmol) N-(2-formylfuro[3,2-c]pyridin-4-yl)benzamide (Example 3A) in acetic acid (1.3 ml) was treated with a solution of 200 mg (1.69 mmol) 3-amino-4,4-difluorobut-2-enenitrile [obtainable by Thorpe reaction of acetonitrile with 2,2-difluoroacetonitrile, cf. Org. React. 15, 1 (1967), ibid. 31, 1 (1984)] in 1-butanol (1.0 ml). The mixture was heated to reflux temperature for 2 h. Upon cooling, the reaction mixture was concentrated under reduced pressure, and the residue was treated with ethyl acetate and saturated aq. sodium bicarbonate solution. The organic layer was separated, washed with brine and with water, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by preparative RP-HPLC (methanol/water+0.1% TFA gradient, final mixture 100% methanol) yielding 28 mg (8% of th.) of the title compound.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux temperature for 2 h
  3. temperatureUpon cooling
  4. concentrationthe reaction mixture was concentrated under reduced pressure
  5. additionthe residue was treated with ethyl acetate and saturated aq. sodium bicarbonate solution
  6. customThe organic layer was separated
  7. washwashed with brine and with water
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by preparative RP-HPLC (methanol/water+0.1% TFA gradient, final mixture 100% methanol)

Sources & evidence

ORD record
ord-cc8593d4bc454b189a3680886ff4ecff
Source dataset
uspto-grants-2013_12
Patent number
US08604028B2

Reaction notes

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