Diisopropylethylamine → 5-Cyclopropyl-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (1-ethyl-1-hydroxymethyl-propyl)-amide

HRID 1480110Notes

Reaction equation

HRID 1480110 reaction equation
[CH:1]1([C:4]2[C:5]([O:13][CH2:14][C:15]([F:18])([F:17])[F:16])=[CH:6][C:7]([C:10]([OH:12])=O)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.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.[NH2:52][C:53]([CH2:58][CH3:59])([CH2:56][CH3:57])[CH2:54][OH:55].C(=O)(O)[O-].[Na+]>CN(C=O)C>[CH2:56]([C:53]([NH:52][C:10]([C:7]1[CH:6]=[C:5]([O:13][CH2:14][C:15]([F:18])([F:17])[F:16])[C:4]([CH:1]2[CH2:2][CH2:3]2)=[CH:9][N:8]=1)=[O:12])([CH2:54][OH:55])[CH2:58][CH3:59])[CH3:57]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 143256072-Amino-2-ethylbutan-1-olHCID 902036745-Cyclopropyl-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid

Product 1

HCID 902149355-Cyclopropyl-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (1-ethyl-1-hydroxymethyl-propyl)-amideYield 58%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-Cyclopropyl-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (Example 48c, 20 mg, 77 μmol) in DMF (1.5 mL) was added HATU (32 mg, 84 μmol) and DIPEA (15 μl, 84 μmol). The reaction mixture was stirred at roomtemperature for 20 minutes followed by addition of 2-amino-2-ethylbutan-1-ol (CAN 19792-52-0, 10 mg, 84 μmol). The reaction was stirred at room temperature overnight and was poured into 15 mL of a saturated aqueous solution of sodium bicarbonate. The solution was extracted three times with 10 mL dichloromethane. The organic phases were combined, dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica, eluting with a heptane/ethylacetate gradient to yield the titled compound (16 mg, 58%) as white solid. MS (ESI, m/z): 361.1 (M+H+).

Workup

  1. stirringThe reaction was stirred at room temperature overnight
  2. extractionThe solution was extracted three times with 10 mL dichloromethane
  3. dry with materialdried over sodium sulfate
  4. customevaporated down to dryness
  5. customThe crude material was purified by flash chromatography on silica
  6. washeluting with a heptane/ethylacetate gradient

Sources & evidence

ORD record
ord-00a3cd1ccf75476b897a7fc86be628dc
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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