1,3-Dibromopropane → HCID 67224686, compound

HRID 2036342Notes

Reaction equation

HRID 2036342 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.CC(N=C(N(C)C)N(C)C)(C)C>CN(C=O)C.[Cl-].[Na+].O.O>[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C: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

9

Reactant 5

HCID 80011,3-DibromopropaneHCID 11430Potassium CarbonateHCID 35715812-tert-Butyl-1,1,3,3-tetramethylguanidineHCID 46856371(3R)-3-Aminotetrahydrofuran hydrochlorideHCID 178450357HCID 178450357, compound

Product 1

HCID 67224686HCID 67224686, compoundYield 6.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
20 °C

Procedure

2-(Butyloxy)-8-(methyloxy)-1H-purin-6-amine trifluoroacetate (100 mg, 0.285 mmol) and K2CO3 (98 mg, 0.712 mmol) was stirred in DMF (2 ml) at 50° C. for 1 hour. The reaction was cooled and 1,3-dibromopropane (0.029 ml, 0.285 mmol) was added. The mixture was stirred at 20° C. for 40 mins. (3R)-Tetrahydro-3-furanamine hydrochloride (35.2 mg, 0.285 mmol) and N″-(1,1-dimethylethyl)-N,N,N′,N′-tetramethylguanidine (146 mg, 0.854 mmol) were stirred in DMF 1 ml at 20° C. for 40 mins. The resultant mixture of assumed free base was added to the first reaction vessel and the mixture stirred for 16 hours at 20° C. Water (2 ml) and brine (2 ml) were added to the mixture. The product was extracted with DCM (2×5 ml) using a hydrophobic separation cartridge and the solvent removed on the N2 blowdown unit. The sample was 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 (7 mg).

Workup

  1. temperatureThe reaction was cooled
  2. additionThe resultant mixture of assumed free base
  3. additionwas added to the first reaction vessel
  4. stirringthe mixture stirred for 16 hours at 20° C
  5. extractionThe product was extracted with DCM (2×5 ml)
  6. customthe solvent removed on the N2 blowdown unit
  7. dissolutionThe sample was dissolved in 1:1 MeOH
  8. customDMSO (1 ml) and purified by Mass Directed AutoPrep (Method A)
  9. customThe solvent was dried under a stream of nitrogen

Sources & evidence

ORD record
ord-0271de64d5994b8cbf935c72536af41d
Source dataset
uspto-grants-2013_11
Patent number
US08575181B2

Reaction notes

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