N-{2-(2-Cyano-3-oxobut-1-en-1-yl)furo[3,2-c]pyridin-4-yl}benzamide → N-{2-[3,5-Dicyano-2-(difluoromethyl)-6-methyl-1,4-dihydropyridin-4-yl]furo[3,2-c]pyridin-4-yl}-benzamide

HRID 1910663Notes

Reaction equation

HRID 1910663 reaction equation
[C:1]([C:3]([C:23](=O)[CH3:24])=[CH:4][C:5]1[O:13][C:12]2[CH:11]=[CH:10][N:9]=[C:8]([NH:14][C:15](=[O:22])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C:7]=2[CH:6]=1)#[N:2].[NH2:26][C:27]([CH:31]([F:33])[F:32])=[CH:28][C:29]#[N:30]>CC(O)C>[C:29]([C:28]1[CH:4]([C:5]2[O:13][C:12]3[CH:11]=[CH:10][N:9]=[C:8]([NH:14][C:15](=[O:22])[C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=4)[C:7]=3[CH:6]=2)[C:3]([C:1]#[N:2])=[C:23]([CH3:24])[NH:26][C:27]=1[CH:31]([F:33])[F:32])#[N:30]

Participants

4

Reactant 2

HCID 67154537N-{2-(2-Cyano-3-oxobut-1-en-1-yl)furo[3,2-c]pyridin-4-yl}benzamideHCID 762236343-Amino-4,4-difluorobut-2-enenitrile

Product 1

HCID 52938681N-{2-[3,5-Dicyano-2-(difluoromethyl)-6-methyl-1,4-dihydropyridin-4-yl]furo[3,2-c]pyridin-4-yl}-benzamide

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of 200 mg (0.604 mmol) N-{2-(2-cyano-3-oxobut-1-en-1-yl)furo[3,2-c]pyridin-4-yl}benzamide (Example 4A) and 285 mg (2.41 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 2-propanol (1 ml) was stirred at reflux for 12 h. Upon cooling, the mixture was concentrated under reduced pressure, and the residue was directly purified by preparative RP-HPLC (acetonitrile/water+0.1% TFA gradient, final mixture 90:10 v/v) to yield 176 mg (67% of th.) of the racemic title compound.

Workup

  1. temperatureat reflux for 12 h
  2. temperatureUpon cooling
  3. concentrationthe mixture was concentrated under reduced pressure
  4. customthe residue was directly purified by preparative RP-HPLC (acetonitrile/water+0.1% TFA gradient, final mixture 90:10 v/v)

Sources & evidence

ORD record
ord-007fa4523c5f451c8d8044b8ff18e4a6
Source dataset
uspto-grants-2013_12
Patent number
US08604028B2

Reaction notes

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