Triethylamine → 5-Bromo-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (methyl-cyano-cyclopropyl-methyl)-amide

HRID 1480139Notes

Reaction equation

HRID 1480139 reaction equation
[Br: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.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)CC)C.[NH2:46][C:47]([CH:51]1[CH2:53][CH2:52]1)([CH3:50])[C:48]#[N:49]>C(OC(=O)C)C.CN(C=O)C>[CH3:50][C:47]([NH:46][C:8]([C:5]1[CH:4]=[C:3]([O:11][CH2:12][C:13]([F:16])([F:15])[F:14])[C:2]([Br:1])=[CH:7][N:6]=1)=[O:10])([C:48]#[N:49])[CH:51]1[CH2:53][CH2:52]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 37919192-amino-2-cyclopropylpropanenitrileHCID 902041215-Bromo-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid

Product 1

HCID 1185541735-Bromo-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (methyl-cyano-cyclopropyl-methyl)-amideYield 70%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-Bromo-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (Example 78d, 1.0 g, 3.33 mmol) dry DMF (15 ml) were added TBTU (1.12 g, 3.5 mmol) and triethylamine (675 mg, 929 μl, 6.67 mmol). The reaction mixture was stirred at room temperature for 30 minutes followed by addition of 2-amino-2-cyclopropylpropanenitrile (CAN 37024-73-0, 404 mg, 3.67 mmol). The reaction was stirred at room temperature for 18 hours. The reaction mixture was poured into a separatory funnel, diluted with ethylacetate and extracted with an 1.0M aqueous solution of sodium bicarbonate. The organic phase was collected and the aqueous phase was back-extracted with ethylacetate. 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 a heptane/ethylacetate gradient to yield the title compound (910 mg, 70%) as a light yellow oil. MS (ESI, m/z): 392.3 (M+H+).

Workup

  1. stirringThe reaction was stirred at room temperature for 18 hours
  2. additionThe reaction mixture was poured into a separatory funnel
  3. extractionextracted with an 1.0M aqueous solution of sodium bicarbonate
  4. customThe organic phase was collected
  5. extractionthe aqueous phase was back-extracted with ethylacetate
  6. dry with materialdried over sodium sulfate
  7. customevaporated down to dryness
  8. customThe crude material was purified by flash chromatography on silica eluting a heptane/ethylacetate gradient

Sources & evidence

ORD record
ord-c2a91b47121c4a3e81cf015ebf18cd43
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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