Diisopropylethylamine → Methyl 2-methyl-2-(5-methyl-6-(2,2,2-trifluoroethoxy)picolinamido)propanoate

HRID 927335Notes

Reaction equation

HRID 927335 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:14]([OH:16])=O)=[N:6][C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].Cl.[CH3:18][O:19][C:20](=[O:25])[C:21]([CH3:24])([CH3:23])[NH2:22].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:23][C:21]([NH:22][C:14](=[O:16])[C:5]1[CH:4]=[CH:3][C:2]([CH3:1])=[C:7]([O:8][CH2:9][C:10]([F:11])([F:12])[F:13])[N:6]=1)([CH3:24])[C:20]([O:19][CH3:18])=[O:25]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 13258034Methyl 2-aminoisobutyrate hydrochlorideHCID 710875095-Methyl-6-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid

Product 1

HCID 71087523Methyl 2-methyl-2-(5-methyl-6-(2,2,2-trifluoroethoxy)picolinamido)propanoateYield 123.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 5-methyl-6-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (30 mg, 128 μmol), 2-methyl-alanine methyl ester hydrochloride (23.5 mg, 153 μmol), HATU (CAN 148893-10-1, 97.0 mg, 255 μmol) and DIEA (82.4 mg, 109 μl, 638 μmol) in DMF was stirred at ambient temperature for 72 h. The crude reaction mixture was concentrated in vacuo to give 53 mg of a yellow solid. This solid was purified by preparative TLC (silica gel, 2.0 mm, 1:1 heptane/i-PrOAc) and eluted from the silica gel with i-PrOAc. Filtration over speedex and evaporation under reduced pressure provided the title compound (10 mg, 23%) as colorless liquid, MS (EI): m/e=335.2 [M+H]+.

Workup

  1. customThe crude reaction mixture
  2. concentrationwas concentrated in vacuo

Sources & evidence

ORD record
ord-05e699a02409423684e27be35afb8149
Source dataset
uspto-grants-2016_03
Patent number
US09290451B2

Reaction notes

Loading…