Propargyl alcohol → 3-(2-(4-(Pyridin-2-ylamino)phenoxy)pyridin-3-YL)prop-2-YN-1-OL

HRID 473632Notes

Reaction equation

HRID 473632 reaction equation
I[C:2]1[C:3]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[CH2:29]([OH:32])[C:30]#[CH:31]>C1COCC1.[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>[N:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[NH:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][C:3]2[C:2]([C:31]#[C:30][CH2:29][OH:32])=[CH:7][CH:6]=[CH:5][N:4]=2)=[CH:10][CH:11]=1

Participants

7

Reactant 3

HCID 7859Propargyl alcoholHCID 8471TriethylamineHCID 59373959N-(4-(3-Iodopyridin-2-yloxy)phenyl)pyridin-2-amine

Product 1

HCID 593739563-(2-(4-(Pyridin-2-ylamino)phenoxy)pyridin-3-YL)prop-2-YN-1-OL

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of N-(4-(3-iodopyridin-2-yloxy)phenyl)pyridin-2-amine (0.300 g, 0.771 mmol), copper(I) iodide (3.91 μL, 0.116 mmol), trans-dichlorobis(triphenyl-phosphine)palladium (II) (0.034 g, 0.048 mmol), triethylamine (0.800 mL, 5.74 mmol) and propargyl alcohol (0.150 mL, 2.54 mmol) in THF (5 mL) was stirred at rt under an atmosphere of argon for 3.5 h. The reaction was evaporated onto silica gel and purified by flash chromatography (Isco, (60 gram)) eluting with 2M NH3 in MeOH:CH2Cl2 (0:1→3:97). The material was stirred over MeOH, filtered and dried in vacuo to give a white crystalline solid. MS (ESI, pos. ion) m/z: 318.0. IC50 (uM)=0.2612.

Workup

  1. customThe reaction was evaporated onto silica gel
  2. custompurified by flash chromatography (Isco, (60 gram))
  3. washeluting with 2M NH3 in MeOH:CH2Cl2 (0:1→3:97)
  4. stirringThe material was stirred over MeOH
  5. filtrationfiltered
  6. customdried in vacuo
  7. customto give a white crystalline solid

Sources & evidence

ORD record
ord-d52139cd7bfe4774b7879c522f277c8e
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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