Water → 6-((9H-purin-9-yl)methyl)-2-(methylthio)benzo[d]oxazole

HRID 1848116Notes

Reaction equation

HRID 1848116 reaction equation
[N:1]1[CH:9]=[C:8]2[C:4]([NH:5][CH:6]=[N:7]2)=[N:3][CH:2]=1.[H-].[Na+].Cl[CH2:13][C:14]1[CH:24]=[CH:23][C:17]2[N:18]=[C:19]([S:21][CH3:22])[O:20][C:16]=2[CH:15]=1.O>CN(C=O)C>[N:1]1[CH:9]=[C:8]2[C:4]([N:5]([CH2:13][C:14]3[CH:24]=[CH:23][C:17]4[N:18]=[C:19]([S:21][CH3:22])[O:20][C:16]=4[CH:15]=3)[CH:6]=[N:7]2)=[N:3][CH:2]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 866810166-(Chloromethyl)-2-(methylthio)benzo[d]oxazoleHCID 178420877HCID 178420877, compound

Product 1

HCID 866810896-((9H-purin-9-yl)methyl)-2-(methylthio)benzo[d]oxazoleYield 32.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 9H-purine (784 mg, 6.53 mmol) in DMF (16 mL) was added NaH (60% dispersion in mineral oil, 373 mg, 9.33 mmol), portionwise at 0° C. After stirring for 30 min, 6-(chloromethyl)-2-(methylthio)benzo[d]oxazole (1.3 g, 6.22 mmol) was added to the mixture. The reaction mixture was allowed to warm to rt and stir for 3 h. The reaction mixture was poured into water (150 mL) and extracted with ethyl acetate (150 mL×4). The combined organic layers were washed with water and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 40:1 DCM/MeOH to give 6-((9H-purin-9-yl)methyl)-2-(methylthio)benzo[d]oxazole as a light yellow solid (569 mg, 32.7%). 1H NMR (300 MHz, DMSO-d6) δ 9.14 (s, 1H), 8.92 (s, 1H), 8.77 (s, 1H), 7.69 (s, 1H), 7.56 (d, J=7.8 Hz, 1H), 7.35 (d, J=9.0 Hz, 1H), 5.59 (s, 2H), 2.70 (s, 3H). LCMS (ESI) m/z 298 (M+H)+.

Workup

  1. customportionwise at 0° C
  2. stirringstir for 3 h
  3. extractionextracted with ethyl acetate (150 mL×4)
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with 40:1 DCM/MeOH

Sources & evidence

ORD record
ord-8957551d8fdb4885bf07ba165980abd8
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

Loading…