4-Methylmorpholine → 3-(2,2-Difluoro-propionylamino)-5-(5-methyl-pyridin-2-yl)-benzoic acid methyl ester

HRID 84754Notes

Reaction equation

HRID 84754 reaction equation
[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][N:11]=2)[CH:7]=[C:6]([NH2:17])[CH:5]=1.[F:19][C:20]([F:25])([CH3:24])[C:21](O)=[O:22].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>C(#N)C>[CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][N:11]=2)[CH:7]=[C:6]([NH:17][C:21](=[O:22])[C:20]([F:25])([F:19])[CH3:24])[CH:5]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 27828252,2-Difluoropropionic acidHCID 57851018Methyl 3-amino-5-(5-methylpyridin-2-yl)benzoate

Product 1

HCID 578513043-(2,2-Difluoro-propionylamino)-5-(5-methyl-pyridin-2-yl)-benzoic acid methyl esterYield 65.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

3-Amino-5-(5-methyl-pyridin-2-yl)-benzoic acid methyl ester (0.7 g, 2.89 mmol, from Preparation 2), 2,2-difluoropropionic acid (0.370 g, 2.89 mmol), EDCI (4.34 mmol), and HOBt (4.34 mmol) and NMM (14.45 mmol) were added to 25 mL of acetonitrile. The reaction mixture was stirred at room temperature for 21 hours, after which the acetonitrile was removed under reduced pressure. The residue was partitioned between water and EtOAc, and the combined organic layers were washed with water, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (EtOAc/hexanes 35:1) to give 0.630 g of 3-(2,2-difluoro-propionylamino)-5-(5-methyl-pyridin-2-yl)-benzoic acid methyl ester as a white solid, MS (M+H)=335.

Workup

  1. customafter which the acetonitrile was removed under reduced pressure
  2. customThe residue was partitioned between water and EtOAc
  3. washthe combined organic layers were washed with water
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography (EtOAc/hexanes 35:1)

Sources & evidence

ORD record
ord-8e635087ac994b918c32f440965632a8
Source dataset
uspto-grants-2014_09
Patent number
US08846945B2

Reaction notes

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