Phenylacetylene → 4-Chloro-6-(phenylethynyl)pyrimidin-5-amine

HRID 1261318Notes

Reaction equation

HRID 1261318 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)#[CH:2].[Cl:9][C:10]1[C:15]([NH2:16])=[C:14](Cl)[N:13]=[CH:12][N:11]=1.CCN(C(C)C)C(C)C>COCCOC.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[Cl:9][C:10]1[C:15]([NH2:16])=[C:14]([C:2]#[C:1][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)[N:13]=[CH:12][N:11]=1

Participants

8

Reactant 3

HCID 10821PhenylacetyleneHCID 794345-Amino-4,6-dichloropyrimidineHCID 81531Diisopropylethylamine

Product 1

HCID 594245784-Chloro-6-(phenylethynyl)pyrimidin-5-amineYield 22%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

Ethynylbenzene (0.092 mL, 0.92 mmol) was added to a solution of 4,6-dichloropyrimidin-5-amine (100 mg, 0.61 mmol), Pd(PPh3)4 (140 mg, 0.12 mmol), CuI (116 mg, 0.61 mmol) and DIPEA (0.5 mL, 3.05 mmol) in DME (6.1 mL). The reaction mixture was stirred in the dark over night at room temperature, diluted with DCM, washed sequentially with dilute aqueous citric acid and water, dried over anhydrous Na2SO4 and concentrated under reduce pressure. The residue was purified by flash chromatography, eluent EtOAc/hexane (1:3), to afford title compound 251 (30.8 mg, 22% yield) as a yellow solid. MS (m/z): 230.1 (100.0%), 232.1 (33%) (M+1).

Workup

  1. washwashed sequentially with dilute aqueous citric acid and water
  2. dry with materialdried over anhydrous Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified by flash chromatography, eluent EtOAc/hexane (1:3)

Sources & evidence

ORD record
ord-d21663a5ff9143fdaa81b2d721ddd7b8
Source dataset
uspto-grants-2013_06
Patent number
US08470850B2

Reaction notes

Loading…