Lithium Chloride → 2-(4-(7-(Trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl)pyrimidin-2-yl)benzonitrile

HRID 1796024Notes

Reaction equation

HRID 1796024 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][C:15]([C:17]([F:20])([F:19])[F:18])=[N:16][C:11]3=[N:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1.C([Sn](CCCC)(CCCC)[C:26]1[CH:33]=[CH:32][CH:31]=[CH:30][C:27]=1[C:28]#[N:29])CCC.[Cl-].[Li+]>CN(C)C(=O)C.[Cu]I.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[F:18][C:17]([F:20])([F:19])[C:15]1[CH:14]=[CH:13][N:12]2[C:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([C:26]4[CH:33]=[CH:32][CH:31]=[CH:30][C:27]=4[C:28]#[N:29])[N:7]=3)=[CH:9][N:10]=[C:11]2[N:16]=1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 98574753-(2-Chloropyrimidin-4-yl)-7-(trifluoromethyl)imidazo[1,2-a]pyrimidineHCID 110797022-Tributylstannylbenzonitrile

Product 1

HCID 101094602-(4-(7-(Trifluoromethyl)imidazo[1,2-a]pyrimidin-3-yl)pyrimidin-2-yl)benzonitrileYield 11.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

To a degassed solution of the product of Example 5 (70 mg, 0.23 mmol) in N,N-dimethylacetamide (2 ml) was added 2-tributylstannylbenzonitrile (183 mg, 0.46 mmol), lithium chloride (27.5 mg, 0.58 mmol), copper(I) iodide (5 mg) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (9 mg) and the mixture heated at 90° C. for 4 h. After cooling to ambient temperature the reaction was poured onto a strong cation exchange cartridge and eluted with methanol. The product was then eluted with a 2.0M solution of ammonia in methanol and evaporated in vacuo. The residue was dissolved in 5% methanol in dichloromethane and applied to two preparative TLC plates (silica gel) and eluted with 1:1 ethyl acetate in isohexane. The appropriate band was collected and processed to give a solid which was recrystallised from dichloromethane/ethyl acetate/isohexane to give 2-[4-(7-trifluoromethylimidazo[1,2-α]pyrimidin-3-yl)pyrimidin-2-yl]benzonitrile (10 mg) as a white solid: δH (400 MHz, CDCl3) 7.50 (1H, d, J 7.4), 7.65-7.69 (1H, m), 7.78-7.82 (2H, m), 7.94 (1H, dd, J 7.8 and 1.2), 8.34 (1H, dd, J 8.0 and 1.0), 8.74 (1H, s), 8.97 (1H, d, J 5.5), 10.74 (1H, d, J 7.4); m/z (ES+) 366 (M++H).

Workup

  1. temperatureAfter cooling to ambient temperature the reaction
  2. additionwas poured onto a strong cation exchange cartridge
  3. washeluted with methanol
  4. washThe product was then eluted with a 2.0M solution of ammonia in methanol
  5. customevaporated in vacuo
  6. dissolutionThe residue was dissolved in 5% methanol in dichloromethane
  7. washeluted with 1:1 ethyl acetate in isohexane
  8. customThe appropriate band was collected
  9. customto give a solid which
  10. customwas recrystallised from dichloromethane/ethyl acetate/isohexane

Sources & evidence

ORD record
ord-31cf831063f64c60b51698dc5fed087a
Source dataset
uspto-grants-2006_04
Patent number
US07030128B2

Reaction notes

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