Cyanogen Bromide → HCID 59160647, compound

HRID 1500056Notes

Reaction equation

HRID 1500056 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]1[N:16]=[C:15]([NH2:17])[C:14]([F:18])=[CH:13][N:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[N:19]#[C:20]Br>C1COCC1.C(=O)(O)[O-].[Na+]>[CH2:3]([O:10][C:11]1[N:16]=[C:15]([NH:17][C:20]#[N:19])[C:14]([F:18])=[CH:13][N:12]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 3

HCID 10476Cyanogen BromideHCID 24758Sodium hydrideHCID 57818833HCID 57818833, compound

Product 1

HCID 59160647HCID 59160647, compoundYield 77.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 516892Sodium BicarbonateSolvent

Procedure

To a mixture of sodium hydride (0.65 g, 0.27 mol) in dry THF (10 mL), was added 2-benzyloxy-5-fluoro-pyrimidin-4-yl amine (2.0 g, 0.009 mol) dissolved in THF (15 mL) at room temperature under nitrogen. The mixture was allowed to stir at room temperature for 30 min and then cyanogen bromide (1.45 g, 0.0136 mol) in THF (10 ml) was added to the reaction mixture and allowed stir at room temperature for 16 h. The reaction was diluted with sat. sodium bicarbonate (2×5 mL) and extracted with EtOAc (3×40 mL). The organic phase was dried over Na2SO4, and concentrated to a give a crude solid which was recrystallized by adding minimum quantity of ethyl acetate and hexane until solution became turbid. The solvent was decanted and a gummy brown solid was obtained. The gummy brown solid was rinsed with Et2O (2×10 mL) and allowed to stand in Et2O while stirring for 1 h, until a free solid formed. The resulting solid was filtered and dried to give the title compound (1.7 g, 77%) as a pale brown solid: mp 150-152 dec.; 1H NMR (300 MHz, DMSO-d6) δ 7.80 (bs, 1H), 7.43 (m, 5H), 5.20 (s, 2H); MS (EI) m/z 245 (M)+.

Workup

  1. stirringallowed stir at room temperature for 16 h
  2. extractionextracted with EtOAc (3×40 mL)
  3. dry with materialThe organic phase was dried over Na2SO4
  4. concentrationconcentrated to
  5. customa give a crude solid which
  6. customwas recrystallized
  7. additionby adding minimum quantity of ethyl acetate and hexane until solution
  8. customThe solvent was decanted
  9. customa gummy brown solid was obtained
  10. washThe gummy brown solid was rinsed with Et2O (2×10 mL)
  11. stirringwhile stirring for 1 h, until a free solid
  12. customformed
  13. filtrationThe resulting solid was filtered
  14. customdried

Sources & evidence

ORD record
ord-018019198eef408092dc997bcc88f67b
Source dataset
uspto-grants-2015_12
Patent number
US09204653B2

Reaction notes

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