Triethylamine → HCID 67353219, compound

HRID 75804Notes

Reaction equation

HRID 75804 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10](=[O:27])[NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:22]=[C:21]([C:23](O)=[O:24])[O:20][N:19]=2)=[CH:14][C:13]=1[CH3:26].ON1C2C=CC=CC=2N=N1.Cl.[CH3:39][O:40][C:41](=[O:47])[C@H:42]([CH:44]([CH3:46])[CH3:45])[NH2:43].C(N(CC)CC)C>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10](=[O:27])[NH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[CH:22]=[C:21]([C:23]([NH:43][CH:42]([CH:44]([CH3:46])[CH3:45])[C:41]([O:40][CH3:39])=[O:47])=[O:24])[O:20][N:19]=2)=[CH:14][C:13]=1[CH3:26]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 111190Methyl valinate hydrochlorideHCID 673522053-(4-(3-(2,6-Difluorophenyl)ureido)-3-methylphenyl)isoxazole-5-carboxylic acid

Product 1

HCID 67353219HCID 67353219, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

3-(4-(3-(2,6-difluorophenyl)ureido)-3-methylphenyl)isoxazole-5-carboxylic acid (1.0 equiv.) was dissolved in 25 ml of DMF, N,N′-dicyclocarbodiimide (1.2 equiv.) and 1-hydroxybenzotriazole (1.0 equiv.) was added and stirred at room temperature for 10 min. L-valine methyl ester hydrochloride (1.5 equiv.) was neutralized with triethylamine (1.5 equiv.) in 10 ml of DMF and was added to the above mixture and the resulting reaction mixture was stirred at room temperature for 48 hours. DMF was evaporated and then diluted with EtOAc. The organic layer was washed with water, brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was dissolved in a chloroform and methanol mixture, adsorbed on silica (100-200 mesh) and purified by flash chromatography on silica gel, and then eluted with 0-2% methanol in chloroform to obtain a crude product.

Workup

  1. additionwas added to the above mixture
  2. customthe resulting reaction mixture
  3. stirringwas stirred at room temperature for 48 hours
  4. customDMF was evaporated
  5. additiondiluted with EtOAc
  6. washThe organic layer was washed with water, brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue was dissolved in a chloroform and methanol mixture
  11. custompurified by flash chromatography on silica gel
  12. washeluted with 0-2% methanol in chloroform

Sources & evidence

ORD record
ord-059b072d8465424da4fda90939e44e03
Source dataset
uspto-grants-2014_09
Patent number
US08835428B2

Reaction notes

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