Triethylamine → HCID 90103041, compound

HRID 520734Notes

Reaction equation

HRID 520734 reaction equation
[C:1]([NH:5][C:6]([C:8]1[CH:13]=[CH:12][C:11](Br)=[CH:10][N:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:15][C:16]1[CH:21]=[C:20]([C:22]#[C:23][Si](C)(C)C)[CH:19]=[CH:18][N:17]=1.CCN(CC)CC.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[C:1]([NH:5][C:6]([C:8]1[CH:13]=[CH:12][C:11]([C:23]#[C:22][C:20]2[CH:19]=[CH:18][N:17]=[C:16]([Cl:15])[CH:21]=2)=[CH:10][N:9]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 2724141Tetrabutylammonium FluorideHCID 109996962-Pyridinecarboxamide, 5-bromo-N-(1,1-dimethylethyl)-HCID 219853912-Chloro-4-(2-(trimethylsilyl)ethynyl)pyridine

Product 1

HCID 90103041HCID 90103041, compoundYield 73%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

5-Bromo-pyridine-2-carboxylic acid tert-butylamide (Example 1, step 1) (280 mg, 0.92 mmol) was dissolved in THF (20 ml). 2-Chloro-4-trimethylsilanylethynyl-pyridine [CAS 499193-57-6] (222 mg, 1.06 mmol, 1.15 equiv.), Et3N (1.28 ml, 9.2 mmol, 10 equiv.), Bis-(triphenylphosphine)-palladium(II)dichloride (19 mg, 28 μmol, 0.03 equiv.) and copper(I)iodide (5 mg, 28 μmol, 0.03 equiv.) were added under nitrogen and the mixture was heated to 70° C. TBAF 1M in THF (970 μl, 0.97 mmol, 1.05 equiv.) was added dropwise over a period of 20 minutes at 70° C. The reaction mixture was stirred for 2 hours at 70° C. and evaporated in presence of Isolute® sorbent to dryness. The crude product was purified by flash chromatography with a 20 g silica gel column eluting with heptane:ethyl acetate 100:0→0:100. The desired 5-(2-chloro-pyridin-4-ylethynyl)-pyridine-2-carboxylic acid tert-butylamide (210 mg, 73% yield) was obtained as a white solid, MS: m/e=314.4/316.4 (M+H+).

Workup

  1. customevaporated in presence of Isolute® sorbent to dryness
  2. customThe crude product was purified by flash chromatography with a 20 g silica gel column
  3. washeluting with heptane:ethyl acetate 100:0→0:100

Sources & evidence

ORD record
ord-6c7fd11c82d544f68e6612a0bece53df
Source dataset
uspto-grants-2016_05
Patent number
US09328070B2

Reaction notes

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