1,3-Dibromopropane → HCID 67224004, compound

HRID 2036341Notes

Reaction equation

HRID 2036341 reaction equation
F[C:2](F)(F)[C:3]([OH:5])=O.[CH2:8]([O:12][C:13]1[NH:14][C:15]([NH2:24])=[C:16]2[C:20]([N:21]=1)=[N:19][C:18]([O:22][CH3:23])=[N:17]2)[CH2:9][CH2:10][CH3:11].C([O-])([O-])=O.[K+].[K+].Br[CH2:32][CH2:33]CBr.Cl.O1[CH2:41][CH2:40][C@H:39]([NH2:42])C1.[OH-].[Na+].C(N(CC)CC)C>CN(C=O)C.O.C(Cl)Cl>[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([NH:17][CH:18]([O:22][CH3:23])[N:19]2[CH2:41][CH2:40][CH2:39][NH:42][C@H:3]2[CH2:2][CH2:33][CH2:32][O:5]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11]

Participants

10

Reactant 6

HCID 80011,3-DibromopropaneHCID 8471Triethylamine2×HCID 11430Potassium CarbonateHCID 14798Sodium Hydroxide2×HCID 18664284(3S)-oxolan-3-amine hydrochloride2×HCID 178450357HCID 178450357, compound

Product 1

HCID 67224004HCID 67224004, compoundYield 4.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
20 °C

Procedure

2-(Butyloxy)-8-(methyloxy)-1H-purin-6-amine trifluoroacetate (70 mg, 0.199 mmol) was stirred with K2CO3 (68.9 mg, 0.498 mmol) in DMF (1 ml) for 1 hour at 50° C. The reaction mixture was cooled and 1,3-dibromopropane (0.020 ml, 0.199 mmol) was added. The reaction mixture was stirred at 20° C. for 40 mins. (3S)-Tetrahydro-3-furanamine hydrochloride (49.3 mg, 0.399 mmol) was shaken with aqueous NaOH solution (0.996 ml, 1.993 mmol) for 5 mins., DCM, (2×3 ml) was added and the mixture passed through a phase separation cartridge. The solvent was removed under mild conditions by rotary evaporation. The free base was added to the reaction mixture followed by triethylamine (0.056 ml, 0.399 mmol) and the mixture was stirred at 20° C. for 16 hours. (3S)-Tetrahydro-3-furanamine hydrochloride (49.3 mg, 0.399 mmol) was shaken with NaOH (0.996 ml, 1.993 mmol) for 5 mins., DCM (2×3 ml) was added, and the mixture passed through a phase separation cartridge and added directly to the reaction mixture. Triethylamine (0.056 ml, 0.399 mmol) was added and the mixture was stirred at 20° C. for 16 hours. Water was added and the mixture extracted with DCM (2×5 ml) through a hydrophobic frit. The solvent was removed by nitrogen blowdown. The samples were dissolved in 1:1 MeOH:DMSO (1 ml) and purified by Mass Directed AutoPrep (Method A). The solvent was dried under a stream of nitrogen to give the title compound as a white solid (3 mg).

Workup

  1. temperatureThe reaction mixture was cooled
  2. customthe mixture passed through a phase separation cartridge
  3. customThe solvent was removed under mild conditions by rotary evaporation
  4. additionThe free base was added to the reaction mixture
  5. stirringthe mixture was stirred at 20° C. for 16 hours
  6. customthe mixture passed through a phase separation cartridge
  7. additionadded directly to the reaction mixture
  8. stirringthe mixture was stirred at 20° C. for 16 hours
  9. extractionthe mixture extracted with DCM (2×5 ml) through a hydrophobic frit
  10. customThe solvent was removed by nitrogen
  11. dissolutionThe samples were dissolved in 1:1 MeOH
  12. customDMSO (1 ml) and purified by Mass Directed AutoPrep (Method A)
  13. customThe solvent was dried under a stream of nitrogen

Sources & evidence

ORD record
ord-fab25e1fa3984a26879f79cf02b983b0
Source dataset
uspto-grants-2013_11
Patent number
US08575181B2

Reaction notes

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