6-Chloro-4-iodopyridin-3-amine → 6-Chloro-4-((1-methylcyclopropyl)ethynyl)pyridin-3-amine

HRID 513080Notes

Reaction equation

HRID 513080 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4](I)[CH:3]=1.[C:10]([C:12]1([CH3:15])[CH2:14][CH2:13]1)#[CH:11]>CCN(CC)CC.[Cu]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>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:11]#[C:10][C:12]2([CH3:15])[CH2:14][CH2:13]2)[CH:3]=1

Participants

6

Reactant 2

HCID 184070406-Chloro-4-iodopyridin-3-amineHCID 215905601-Ethynyl-1-methylcyclopropane

Product 1

HCID 579081926-Chloro-4-((1-methylcyclopropyl)ethynyl)pyridin-3-amineYield 53%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

To a solution of 6-chloro-4-iodopyridin-3-amine (7.0 g, 28 mmol) in Et3N (100 mL) was added 1-ethynyl-1-methyl-cyclopropane (11.0 g, 137 mmol), CuI (0.53 g, 2.8 mmol) and Pd(PPh3)2Cl2 (1.9 g, 2.8 mmol) under N2 atmosphere. The mixture was refluxed overnight and quenched with H2O (100 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (100 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and purified by chromatography on silica gel (3% EtOAc in Petroleum ether as eluant) to afford 6-chloro-4-((1-methylcyclopropyl)ethynyl)pyridin-3-amine (3.0 g, 53%). 1H-NMR (CDCl3, 300 MHz) δ 7.84 (s, 1H), 7.08 (s, 1H), 4.11 (br s, 2H), 1.37 (s, 3H), 1.03 (t, J=2.4, 2 H) 0.76 (t, J=2.4, 2H).

Workup

  1. temperatureThe mixture was refluxed overnight
  2. customquenched with H2O (100 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (100 mL×3)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. custompurified by chromatography on silica gel (3% EtOAc in Petroleum ether as eluant)

Sources & evidence

ORD record
ord-380b977ba64f4f94a05a18fe0af63e84
Source dataset
uspto-grants-2015_08
Patent number
US09102672B2

Reaction notes

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