Hexamethylphosphoramide → HCID 54596503, compound

HRID 1853150Notes

Reaction equation

HRID 1853150 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([SH:8])[CH:5]=[CH:6][CH:7]=1.CN(P(N(C)C)(N(C)C)=O)C.[H-].[Na+].[NH:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[N:24]=[C:23]1[C:31]1[C:32]([NH2:38])=[N:33][CH:34]=[C:35](Br)[N:36]=1>CCOC(C)=O>[NH:22]1[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[N:24]=[C:23]1[C:31]1[C:32]([NH2:38])=[N:33][CH:34]=[C:35]([S:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)[N:36]=1

Participants

6

Reactant 4

HCID 12679HexamethylphosphoramideHCID 24758Sodium hydrideHCID 75710m-FluorobenzenethiolHCID 529377603-(1H-benzo[d]imidazol-2-yl)-5-bromopyrazin-2-amine

Product 1

HCID 54596503HCID 54596503, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

3-Fluorobenzenethiol (70.49 mg, 46.47 μL, 0.55 mmol) was added to HMPA (1 mL) followed by the addition of sodium hydride (60% dispersion in mineral oil) (24 mg, 0.6 mmol). The reaction mixture was stirred at ambient temperature for 10 minutes then 3-(1H-Benzimidazol-2-yl)-5-bromo-pyrazin-2-amine (80 mg, 0.27 mmol) was added and reaction heated at 110° C. under microwave conditions for 45 minutes. The reaction mixture was cooled to ambient temperature and diluted with EtOAc. The organic layer was washed with water (×2), saturated aqueous NaHCO3 (×1) and brine. (×1), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected and freeze-dried to give the title compound as a yellow solid (10 mg, 11% Yield). 1H NMR (400.0 MHz, CDCl3) δ 76.95-7.0 (1H, m), 7.03-7.06 (1H, m), 7.1-7.13 (1H, m), 7.3-7.4 (2H, m), 7.50-7.55 (1H, m), 7.8-7.85 (1H, m), 8.22 (1H, s) and 10.2 (1H, br s) ppm; MS (ES+) 338.1.

Workup

  1. customreaction
  2. temperatureheated at 110° C. under microwave conditions for 45 minutes
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. washThe organic layer was washed with water (×2), saturated aqueous NaHCO3 (×1) and brine
  5. dry with material(×1), dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  9. customThe fractions were collected
  10. customfreeze-dried

Sources & evidence

ORD record
ord-de54da2c6a1a43d482b00bcc3b427743
Source dataset
uspto-grants-2015_02
Patent number
US08962631B2

Reaction notes

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