Sodium Carbonate → 2-{3-[2-(3,4-Difluorophenyl)pyrimidin-4-yl]-8-fluoroimidazo[1,2-alpha]pyridin-7-yl}propan-2-ol

HRID 1765103Notes

Reaction equation

HRID 1765103 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[F:8].Cl[C:13]1[N:18]=[C:17]([C:19]2[N:23]3[CH:24]=[CH:25][C:26]([C:29]([O:32][Si](CC)(CC)CC)([CH3:31])[CH3:30])=[C:27]([F:28])[C:22]3=[N:21][CH:20]=2)[CH:16]=[CH:15][N:14]=1.C([O-])([O-])=O.[Na+].[Na+]>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.C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C:13]2[N:18]=[C:17]([C:19]3[N:23]4[CH:24]=[CH:25][C:26]([C:29]([OH:32])([CH3:30])[CH3:31])=[C:27]([F:28])[C:22]4=[N:21][CH:20]=3)[CH:16]=[CH:15][N:14]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343373,4-Difluorobenzeneboronic acidHCID 878862453-(2-Chloropyrimidin-4-yl)-8-fluoro-7-[2-(triethylsilyloxy)prop-2-yl]imidazo[1,2-alpha]pyridine

Product 1

HCID 100000682-{3-[2-(3,4-Difluorophenyl)pyrimidin-4-yl]-8-fluoroimidazo[1,2-alpha]pyridin-7-yl}propan-2-ol

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

3,4-Difluorophenylboronic acid (90 mg, 0.57 mmol), 3-(2-chloropyrimidin-4-yl)-8-fluoro-7-[2-(triethylsilyloxy)prop-2-yl]imidazo[1,2-α]pyridine (120 mg, 0.29 mmol), tetrakis(triphenylphosphine)palladium(0) (16 mg, 0.015 mmol), THF (1.4 ml) and aqueous Na2CO3 solution (2M; 0.44 ml) were combined and heated to reflux for 18 h. On cooling, the mixture was partitioned between 2M NaOH solution (2 ml) and CH2Cl2 (3 ml) and the phases separated using a phase-separation cartridge. The organic fraction was purified by column chromatography (silica, 90% EtOAc/isohexane), then the silyl protection removed by treatment with an ethanolic solution of 37% hydrochloric acid (5 drops in 2 ml of ethanol). After 48 h, the solution was concentrated in vacuo and the residue partitioned between EtOAc and saturated aqueous NaHCO3. The organic phase was dried over MgSO4, filtered, concentrated and the residue purified by column chromatography (silica, EtOAc) affording the title compound as a white amorphous solid (158 mg): δH (360 MHz, CDCl3) 1.76 (6H, s), 7.00-7.20 (2H, m), 7.40-7.70 (2H, m), 8.20-8.40 (1H, m), 8.36 (1H, s), 8.80 (1H, m), 9.90-9.92 (1H, m); m/z (ES+) 385 (100%, [MH]+).

Workup

  1. temperatureheated
  2. temperatureto reflux for 18 h
  3. temperatureOn cooling
  4. customthe mixture was partitioned between 2M NaOH solution (2 ml) and CH2Cl2 (3 ml)
  5. customthe phases separated
  6. customThe organic fraction was purified by column chromatography (silica, 90% EtOAc/isohexane)
  7. customthe silyl protection removed by treatment with an ethanolic solution of 37% hydrochloric acid (5 drops in 2 ml of ethanol)
  8. concentrationthe solution was concentrated in vacuo
  9. customthe residue partitioned between EtOAc and saturated aqueous NaHCO3
  10. dry with materialThe organic phase was dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customthe residue purified by column chromatography (silica, EtOAc)

Sources & evidence

ORD record
ord-e66fd568fd124f9a987b28261c7c5820
Source dataset
uspto-grants-2007_06
Patent number
US07226926B2

Reaction notes

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