1,1-Dibromo-1,2,2,2-tetrachloroethane → 8-Bromo-2,6-bis-((R)-3-methyl-morpholin-4-yl)-9-(tetrahydro-pyran-2-yl)-9H-purine

HRID 522804Notes

Reaction equation

HRID 522804 reaction equation
[CH3:1][C@@H:2]1[CH2:7][O:6][CH2:5][CH2:4][N:3]1[C:8]1[N:16]=[C:15]2[C:11]([N:12]=[CH:13][N:14]2[CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][O:18]2)=[C:10]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][C@H:24]2[CH3:29])[N:9]=1.[Br:30]C(Br)(Cl)C(Cl)(Cl)Cl>C1COCC1>[Br:30][C:13]1[N:14]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][O:18]2)[C:15]2[C:11]([N:12]=1)=[C:10]([N:23]1[CH2:28][CH2:27][O:26][CH2:25][C@H:24]1[CH3:29])[N:9]=[C:8]([N:3]1[CH2:4][CH2:5][O:6][CH2:7][C@H:2]1[CH3:1])[N:16]=2

Participants

4

Reactant 2

HCID 137826771,1-Dibromo-1,2,2,2-tetrachloroethaneHCID 895255782,6-Bis-((R)-3-methyl-morpholin-4-yl)-9-(tetrahydro-pyran-2-yl)-9H-purine

Product 1

HCID 895256398-Bromo-2,6-bis-((R)-3-methyl-morpholin-4-yl)-9-(tetrahydro-pyran-2-yl)-9H-purineYield 78.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Diisopropylamine (290 μl, 2.04 mmol) was dissolved in 4 mL of THF at −60° C., when butyllithium in hexane was added (1.27 mL, 2.04 mmol) to form LDA. 2,6-Bis-((R)-3-methyl-morpholin-4-yl)-9-(tetrahydro-pyran-2-yl)-9H-purine (585 mg, 1.45 mmol) was dissolved in 8 mL of THF and added to the reaction mixture at −78° C. within 10 minutes. The reaction was stirred for 1 hour at −78° C. Dibromotetrachloroethane (947 mg, 2.91 mmol) in 4 mL of THF was added within 10 minutes. The reaction was stirred for 2 hours at −78° C. The reaction was quenched by addition of saturated aqueous NH4Cl and warmed to room temperature. The mixture was diluted with 80 mL of EtOAc and 50 mL of brine. The organic layers were separated, dried over Na2SO4, filtered, and concentrated to give a residue, which was purified by column chromatography (30 g SiO2, heptane/TBME in a ratio 7/3) to give the product as a foam (546 mg, 78%).

Workup

  1. additionadded to the reaction mixture at −78° C. within 10 minutes
  2. stirringThe reaction was stirred for 2 hours at −78° C
  3. customThe reaction was quenched by addition of saturated aqueous NH4Cl
  4. temperaturewarmed to room temperature
  5. additionThe mixture was diluted with 80 mL of EtOAc and 50 mL of brine
  6. customThe organic layers were separated
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a residue, which
  11. customwas purified by column chromatography (30 g SiO2, heptane/TBME in a ratio 7/3)

Sources & evidence

ORD record
ord-ae716af2dccc43868f666c67a8df5a3c
Source dataset
uspto-grants-2016_05
Patent number
US09334271B2

Reaction notes

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