Sodium hydride → 5-Amino-3-pyridin-3-ylmethyl-3H-thiazolo[4,5-d]pyrimidin-2-one

HRID 333668Notes

Reaction equation

HRID 333668 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[S:10][C:9](=[O:11])[NH:8][C:6]=2[N:7]=1.[H-].[Na+].Br.Br[CH2:16][C:17]1[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=1>CN(C=O)C>[NH2:1][C:2]1[N:3]=[CH:4][C:5]2[S:10][C:9](=[O:11])[N:8]([CH2:16][C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)[C:6]=2[N:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 127070373-(Bromomethyl)pyridine hydrobromideHCID 247640395-Amino-3H-thiazolo[4,5]pyrimidine-2-one

Product 1

HCID 115506525-Amino-3-pyridin-3-ylmethyl-3H-thiazolo[4,5-d]pyrimidin-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
30 °C

Procedure

5-Amino-3H-thiazolo[4,5-d]pyrimidin-2-one (107 mg, 0.64 mmol) was dissolved in DMF (4 mL) at ambient temperature. Sodium hydride (30 mg, 1.32 mmol) was added and the mixture was heated to 30° C. Stirring was continued for 0.5 h before 3-bromomethyl-pyridine hydrobromide (179 mg, 0.71 mmol) was added. The mixture was then heated to 75° C. and allowed to stir for 4 h. Upon completion, the reaction was allowed to cool to room temperature, then concentrated. Water (12 mL) was added. The resulting mixture was diluted with H2O (12 mL), then extracted with ethyl acetate (3×5 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude material was purified by column chromatography (SiO2, 20-50% EtOAc—CH2Cl2) to generate 90 mg (54%) of 54 as a white solid: 1H NMR (400 MHz, DMSO-d6) δ 8.59 (s, 1H), 8.48 (d, J=3.6, 1H), 8.32 (s, 1H), 7.71 (d, J=8.4, 1H), 7.36 (m, 1H), 6.86 (s, 2H), 5.04 (s, 2H); [M+H]+ 260.1.

Workup

  1. additionwas added
  2. temperatureThe mixture was then heated to 75° C.
  3. stirringto stir for 4 h
  4. temperatureto cool to room temperature
  5. concentrationconcentrated
  6. additionWater (12 mL) was added
  7. additionThe resulting mixture was diluted with H2O (12 mL)
  8. extractionextracted with ethyl acetate (3×5 mL)
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude material was purified by column chromatography (SiO2, 20-50% EtOAc—CH2Cl2)

Sources & evidence

ORD record
ord-797409754a5f4f488652e2f8e2b7c15d
Source dataset
uspto-grants-2014_11
Patent number
US08883758B2

Reaction notes

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