Tetrahydrofuran → 5-Chloro-3-((trimethylsilyl)ethynyl)pyridin-2-amine

HRID 1024408Notes

Reaction equation

HRID 1024408 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](I)[C:5]([NH2:8])=[N:6][CH:7]=1.C1COCC1.C(N(CC)CC)C.[CH3:22][Si:23]([C:26]#[CH:27])([CH3:25])[CH3:24]>[Cu](I)I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:27]#[C:26][Si:23]([CH3:25])([CH3:24])[CH3:22])[C:5]([NH2:8])=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 110760102-Amino-5-chloro-3-iodopyridine

Product 1

HCID 247294655-Chloro-3-((trimethylsilyl)ethynyl)pyridin-2-amineYield 100%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 3283Diethyl EtherSolvent

Procedure

A 250 ml round bottom flask was charged with 5-chloro-3-iodo-pyridin-2-ylamine (1) (42 g, 165 mmol), THF (100 ml), copper iodide (315 mg, 1.65 mmol) and PdCl2(PPh3)2 (1.15 g, 1.65 mmol) under nitrogen. Triethylamine (70 ml, 0.5 mol), and trimethylsilyl acetylene (30 ml, 0.21 mol). The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was then cooled to 0° C. and diethyl ether was added. The suspension was filtered through a celite and thoroughly washed with diethyl ether. The filtrate was concentrated and pre-absorbed onto silica gel and purified by column chromatography using as eluent, pentane/DCM 10% to 100%, to afford an off white solid (36 g, 100%). 1H NMR (CDCl3): 0.3 (9H, s), 5.0-5.1 (2H, brs), 7.6 (1H, s), 7.9 (1H, s). MS (ES+): 225, 227.

Workup

  1. temperatureThe reaction mixture was then cooled to 0° C.
  2. filtrationThe suspension was filtered through a celite
  3. washthoroughly washed with diethyl ether
  4. concentrationThe filtrate was concentrated
  5. custompre-absorbed onto silica gel
  6. custompurified by column chromatography

Sources & evidence

ORD record
ord-67fa9998f1684aa4879d0885e7104c12
Source dataset
uspto-grants-2014_05
Patent number
US08722889B2

Reaction notes

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