2,4-Difluoroaniline → 2-Chloro-N-(2,4-difluorophenyl)-4-iodonicotinamide

HRID 1986088Notes

Reaction equation

HRID 1986088 reaction equation
[Cl:1][C:2]1[N:10]=[CH:9][CH:8]=[C:7]([I:11])[C:3]=1[C:4]([OH:6])=O.[F:12][C:13]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:14]=1[NH2:15].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:1][C:2]1[N:10]=[CH:9][CH:8]=[C:7]([I:11])[C:3]=1[C:4]([NH:15][C:14]1[CH:16]=[CH:17][C:18]([F:20])=[CH:19][C:13]=1[F:12])=[O:6]

Participants

6

Reactant 4

HCID 97092,4-DifluoroanilineHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 177501742-Chloro-4-iodonicotinic acid

Product 1

HCID 577213332-Chloro-N-(2,4-difluorophenyl)-4-iodonicotinamideYield 54.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a homogeneous mixture of 2-chloro-4-iodonicotinic acid (CB Research & Development, Inc., 0.58 g, 2.0 mmol) and 2,4-difluoroaniline (Aldrich, 0.21 mL, 2.0 mmol) in anhydrous DMF (7 mL) was added PyBroP (Novabiochem, 1.4 g, 3.1 mmol) followed by DIPEA (1.1 mL, 6.6 mmol). The mixture was stirred for 63 hours, and then partitioned between chloroform and 10% LiCl (aq). After the aqueous layer was extracted with chloroform, the combined organic layers were washed twice with 10% LiCl (aq), dried over anhydrous MgSO4, and then concentrated in vacuo. Purification of the residue by flash column chromatography (SiO2, eluting with 1:1 hexane/EtOAc) afforded the desired compound (0.43 g, 53%). MS(ESI+) m/z 395 (M+H)+.

Workup

  1. custompartitioned between chloroform and 10% LiCl (aq)
  2. extractionAfter the aqueous layer was extracted with chloroform
  3. washthe combined organic layers were washed twice with 10% LiCl (aq)
  4. dry with materialdried over anhydrous MgSO4
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue
  7. washby flash column chromatography (SiO2, eluting with 1:1 hexane/EtOAc)

Sources & evidence

ORD record
ord-82b843af914a40afad82a3840811096e
Source dataset
uspto-grants-2009_06
Patent number
US07547782B2

Reaction notes

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