Nitrogen → HCID 89708471, compound

HRID 1845896Notes

Reaction equation

HRID 1845896 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:9][C@H:10]([C:12]2[C:17]([Cl:18])=[CH:16][CH:15]=[C:14]([F:19])[C:13]=2[Cl:20])[CH3:11])[C:5]([NH2:8])=[N:6][CH:7]=1.C(N(CC)CC)C.N#N.[C:30]([Si:32]([CH3:35])([CH3:34])[CH3:33])#[CH:31]>C1(C)C=CC=CC=1.[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>[Cl:20][C:13]1[C:14]([F:19])=[CH:15][CH:16]=[C:17]([Cl:18])[C:12]=1[C@@H:10]([O:9][C:4]1[C:5]([NH2:8])=[N:6][CH:7]=[C:2]([C:31]#[C:30][Si:32]([CH3:35])([CH3:34])[CH3:33])[CH:3]=1)[CH3:11]

Participants

8

Reactant 4

HCID 947NitrogenHCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 848193465-Bromo-3-[(1S)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-2-pyridinamine

Product 1

HCID 89708471HCID 89708471, compoundYield 80.6%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
30 °C

Procedure

The compound (S)-5-bromo-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-2-aminopyridine (12.58 g, 33.11 mmol) was dispersed in toluene (100 mL), and triethylamine (14.05 g, 139.06 mmol) and copper iodide (126 mg, 0.66 mmol) were added successively. Under the protection of N2 atmosphere, PdCl2(PPh3)2 (465 mg, 0.66 mmol) was added. The reaction mixture was heated to 30° C., stirred for 0.5 h. Ethynyltrimethylsilane (9.11 g, 92.71 mmol) was added dropwise, gradually warmed to 90° C., and stirred overnight. Through HPLC test, it was found that the raw materials were completely reacted. The reaction liquid was cooled down, washed with water, and the toluene layers were combined. The toluene layer was dried over anhydrous Na2SO4, concentrated; the residue was purified via silica gel column chromatography (petroleum ether:ethyl acetate=3:1) to yield the target product as yellow solid (10.6 g, yield: 80%).

Workup

  1. temperaturegradually warmed to 90° C.
  2. stirringstirred overnight
  3. customwere completely reacted
  4. customThe reaction liquid
  5. temperaturewas cooled down
  6. washwashed with water
  7. dry with materialThe toluene layer was dried over anhydrous Na2SO4
  8. concentrationconcentrated
  9. customthe residue was purified via silica gel column chromatography (petroleum ether:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-885d4328091247e39848fa7a4aae587a
Source dataset
uspto-grants-2015_02
Patent number
US08952002B2

Reaction notes

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