N-bromobutanimide → 8-bromo-2-(((S)-pentan-2-yl)oxy)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

HRID 2367961Notes

Reaction equation

HRID 2367961 reaction equation
[CH3:1][C@H:2]([O:6][C:7]1[N:15]=[C:14]2[C:10]([N:11]=[CH:12][N:13]2[CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)=[C:9]([NH2:22])[N:8]=1)[CH2:3][CH2:4][CH3:5].[Br:23]N1C(=O)CCC1=O>C(Cl)Cl>[Br:23][C:12]1[N:13]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)[C:14]2[C:10]([N:11]=1)=[C:9]([NH2:22])[N:8]=[C:7]([O:6][C@@H:2]([CH3:1])[CH2:3][CH2:4][CH3:5])[N:15]=2

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 576998322-(((S)-pentan-2-yl)oxy)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Product 1

HCID 576998418-bromo-2-(((S)-pentan-2-yl)oxy)-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2-{[(1S)-1-Methylbutyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (1050 g) was dissolved in DCM (10.5 L) to give a yellow/orange solution which was cooled to 0° C. N-Bromosuccinimide (922 g, 1.5 eq) was charged in 3 equal portions 20 mins. apart and the resultant reaction mixture was stirred at 0-5° C. for 4 hours. The reaction was then quenched by addition of a solution of 500 g sodium thiosulfate pentahydrate in 5.0 L water. The resultant biphase was mixed thoroughly at 20° C. and then the phases were separated. The organics were washed again with a solution of 500 g sodium thiosulfate pentahydrate in 5.0 L water then 500 g dipotassium phosphate in 5.0 L water and finally with 5.0 L water. The organic phase was dried over magnesium sulfate (822 g) and evaporated on a rotary evaporator until foaming became prohibitive. The mixture was then solvent-exchanged into methanol by repeated addition and removal of methanol until sufficient DCM had been removed (as confirmed by NMR). The product was afforded as a red/brown gum containing entrained solvent (1.28 kg corrected for solvent, 96% theoretical yield).

Workup

  1. customto give a yellow/orange solution which
  2. customapart and the resultant reaction mixture
  3. customThe reaction was then quenched by addition of a solution of 500 g sodium thiosulfate pentahydrate in 5.0 L water
  4. additionThe resultant biphase was mixed thoroughly at 20° C.
  5. customthe phases were separated
  6. washThe organics were washed again with a solution of 500 g sodium thiosulfate pentahydrate in 5.0 L water
  7. dry with materialThe organic phase was dried over magnesium sulfate (822 g)
  8. customevaporated on a rotary evaporator
  9. additionaddition and removal of methanol until sufficient DCM
  10. customhad been removed (as confirmed by NMR)
  11. customThe product was afforded as a red/brown gum
  12. additioncontaining entrained
  13. customsolvent (1.28 kg corrected for solvent, 96% theoretical yield)

Sources & evidence

ORD record
ord-f170acfe91c149ff829e4c42c7995f11
Source dataset
uspto-grants-2014_04
Patent number
US08703754B2

Reaction notes

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