Diethyl Ether → 2'-Fluoro-5'-[7-(2-methylthiazol-5-yl)imidazo[1,2-alpha]pyrimidin-3-yl]biphenyl-2-carbonitrile

HRID 2183880Notes

Reaction equation

HRID 2183880 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][N:7]2[C:10]([C:13]3[CH:14]=[CH:15][C:16]([F:27])=[C:17]([C:19]4[C:20]([C:25]#[N:26])=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH:18]=3)=[CH:11][N:12]=[C:6]2[N:5]=1)(=O)[CH3:2].[Br-].[Br-].[Br-].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[C:49]([NH2:52])(=[S:51])[CH3:50].C(OCC)C>C(Cl)(Cl)Cl>[F:27][C:16]1[CH:15]=[CH:14][C:13]([C:10]2[N:7]3[CH:8]=[CH:9][C:4]([C:1]4[S:51][C:49]([CH3:50])=[N:52][CH:2]=4)=[N:5][C:6]3=[N:12][CH:11]=2)=[CH:18][C:17]=1[C:19]1[C:20]([C:25]#[N:26])=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 2723949ThioacetamideHCID 101551885'-(7-Acetylimidazo[1,2-alpha]pyrimidin-3-yl)-2'-fluorobiphenyl-2-carbonitrileHCID 21124087Pyridiniumtribromide

Product 1

HCID 101585372'-Fluoro-5'-[7-(2-methylthiazol-5-yl)imidazo[1,2-alpha]pyrimidin-3-yl]biphenyl-2-carbonitrileYield 11%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
50 °C

Procedure

5′-(7-Acetylimidazo[1,2-α]pyrimidin-3-yl)-2′-fluorobiphenyl-2-carbonitrile (80 mg, 0.22 mmol) and pyridinium tribromide (110 mg, 0.34 mmol) in chloroform (5 ml) was stirred at 50° C. for 3 h. Thioacetamide (33 mg, 0.44 mmol) was then added and the reaction stirred at 50° C. for 16 h. The resulting mixture was partitioned between dichloromethane and saturated aqueous sodium hydrogencarbonate solution. The organic extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered and evaporated to dryness. The residue was purified by preparative thin-layer chromatography eluting with dichloromethane containing 5% methanol and 1% conc. ammonia to give a foam. Trituration with diethyl ether afforded 2′-fluoro-5′-[7-(2-methylthiazol-5-yl)imidazo[1,2-α]pyrimidin-3-yl]biphenyl-2-carbonitrile as a yellow solid (10 mg, 11%): δH (400 MHz, DMSO) 2.75 (3H, s), 7.56-7.68 (5H, m), 7.81-7.92 (3H, m), 7.98-8.05 (2H, m), 8.40 (1H, s), 9.12 (1H, s); m/z (ES+) 412 (M++H).

Workup

  1. customThe resulting mixture was partitioned between dichloromethane and saturated aqueous sodium hydrogencarbonate solution
  2. washThe organic extracts were washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe residue was purified by preparative thin-layer chromatography
  7. washeluting with dichloromethane containing 5% methanol and 1% conc. ammonia
  8. customto give a foam

Sources & evidence

ORD record
ord-2051d9ee8de04ca59ed2e54b227c71f6
Source dataset
uspto-grants-2005_05
Patent number
US06900215B2

Reaction notes

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