4-Pentyn-1-ol → 5-[5-Amino-6-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)pyrimidin-4-yl]pent-4-yn-1-ol

HRID 1786952Notes

Reaction equation

HRID 1786952 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:23]([NH2:24])=[C:22](I)[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.[CH2:26]([OH:31])[CH2:27][CH2:28][C:29]#[CH:30]>C(#N)C.C(N(CC)CC)C.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.[Cu]I>[NH2:24][C:23]1[C:22]([C:30]#[C:29][CH2:28][CH2:27][CH2:26][OH:31])=[N:21][CH:20]=[N:19][C:18]=1[NH:17][C:4]1[CH:5]=[CH:6][C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=2)=[C:2]([Cl:1])[CH:3]=1

Participants

6

Reactant 2

HCID 793464-Pentyn-1-ol2×HCID 86615762N4-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-iodopyrimidine-4,5-diamine

Product 1

HCID 675209565-[5-Amino-6-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)pyrimidin-4-yl]pent-4-yn-1-olYield 57.8%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 178418476HCID 178418476, compoundCatalyst2×HCID 21895542Acetonitrile triethylamineSolvent

Procedure

To a solution of N4-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-iodopyrimidine-4,5-diamine (300 mg) and 4-pentyn-1-ol (65 mg) in acetonitrile-triethylamine (6.0 mL-4.5 mL) were added bis(triphenylphosphine)palladium(II) dichloride (22.5 mg) and copper(I) iodide (7.3 mg) at room temperature, and the mixture was stirred at room temperature under an argon atmosphere for 24 hrs. 4-Pentyn-1-ol (65 mg), bis(triphenylphosphine)palladium(II) dichloride (22.5 mg) and copper(I) iodide (7.3 mg) were added to the reaction system and the mixture was stirred at 60° C. for 2 hrs. After concentration under reduced pressure, the residue was separated and purified by column chromatography (basic silica gel, eluent, ethyl acetate→methanol:ethyl acetate=1:19) to give the title compound (157.2 mg) as a yellow solid.

Workup

  1. stirringthe mixture was stirred at 60° C. for 2 hrs
  2. concentrationAfter concentration under reduced pressure
  3. customthe residue was separated
  4. custompurified by column chromatography (basic silica gel, eluent, ethyl acetate→methanol:ethyl acetate=1:19)

Sources & evidence

ORD record
ord-a0a2b5f3923741ff9192ba6e69b1b3df
Source dataset
uspto-grants-2009_03
Patent number
US07507740B2

Reaction notes

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