Diisopropylethylamine → 5-Chloro-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid ((S)-2,2-dimethyl-1-methylcarbamoyl-propyl)-amide

HRID 1480073Notes

Reaction equation

HRID 1480073 reaction equation
[Cl:1][C:2]1[C:3]([O:11][CH2:12][C:13]([F:16])([F:15])[F:14])=[CH:4][C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.CCN(C(C)C)C(C)C.[NH2:26][C@@H:27]([C:32]([CH3:35])([CH3:34])[CH3:33])[C:28]([NH:30][CH3:31])=[O:29]>CN(C=O)C>[CH3:33][C:32]([CH3:35])([CH3:34])[C@H:27]([NH:26][C:8]([C:5]1[CH:4]=[C:3]([O:11][CH2:12][C:13]([F:16])([F:15])[F:14])[C:2]([Cl:1])=[CH:7][N:6]=1)=[O:10])[C:28](=[O:29])[NH:30][CH3:31]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 445856(2S)-2-Amino-N,3,3-trimethylbutanamideHCID 902040145-Chloro-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid

Product 1

HCID 762822495-Chloro-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid ((S)-2,2-dimethyl-1-methylcarbamoyl-propyl)-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-Chloro-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (Example 24c, 72 mg, 282 μmol) in DMF (1 mL) was added 4-(4,6-dimethoxyl-1,3,5-triazin-2-yl)-4-methylmorpholininium chloride (CAN 3945-69-5, 82 mg, 296 μmol) and DIEA (34.5 μL, 296 μmol). The reaction mixture was then stirred at room temperature for 30 min, followed by addition of (S)-2-amino-N,3,3-trimethylbutanamide (CAN 89226-12-0, 43 mg, 296 μmol). The reaction mixture was stirred for 3 h. The crude reaction mixture was directly purified by preparative HPLC to deliver the desired compound (65 mg, 60%) as white solid. MS (ESI, m/z): 382.4 (M+H+).

Workup

  1. stirringThe reaction mixture was stirred for 3 h
  2. customThe crude reaction mixture
  3. customwas directly purified by preparative HPLC

Sources & evidence

ORD record
ord-59626d13113742f184c3e4a025402762
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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