1-Bromo-3-chloropropane → 9-(3-Chloropropyl)-2-butoxy-8-methoxy-9H-purin-6-amine

HRID 2038176Notes

Reaction equation

HRID 2038176 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([O:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[C:18]([O:22][CH3:23])[NH:19]2)=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11].C(=O)([O-])[O-].[K+].[K+].Br[CH2:32][CH2:33][CH2:34][Cl:35]>CN(C=O)C>[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[CH2:32][CH2:33][CH2:34][Cl:35])=[C:15]([NH2:24])[N:14]=1)[CH2:9][CH2:10][CH3:11]

Participants

5

Reactant 3

HCID 80061-Bromo-3-chloropropaneHCID 11430Potassium CarbonateHCID 178450370HCID 178450370, compound2×

Product 1

HCID 592526379-(3-Chloropropyl)-2-butoxy-8-methoxy-9H-purin-6-amineYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

2-(Butyloxy)-8-(methyloxy)-9H-purin-6-amine trifluoroacetic acid salt (for example, as prepared for Intermediate 6) (4.7 g, 13.38 mmol) and potassium carbonate (4.62 g, 33.4 mmol) in dry DMF (50 mL) were stirred and heated at 50° C., under nitrogen, for 75 min. The mixture was allowed to cool to room temperature and then cooled to 0° C. and 1-bromo-3-chloropropane (commercially available, for example, from Aldrich) (2.106 g, 13.38 mmol) was added. The mixture was stirred at 0 to 10° C. for approximately 5 hours then allowed to warm to room temperature and stirred for approximately a further 40 hours when LCMS indicated approximately 70% of the desired product. The mixture was allowed to settle and the supernatant was pipetted off and the solvent evaporated on a rotary evaporator using a high vacuum pump at about 23° C. Chloroform and water was added to the combined residues which were stirred and the phases separated using a hydrophobic frit. The aqueous layer was re-extracted with further portions of chloroform and the combined chloroform extracts were evaporated under high vacuum at 23° C. to give a yellow solid (2.798 g). This crude material was combined with similar material obtained from two similar preparations (0.56 g and 0.995 g) and purified by flash column chromatography on silica using 2:1 ethyl acetate/chloroform as eluant to give the title compound as an off-white solid (3.011 g).

Workup

  1. temperatureto cool to room temperature
  2. temperaturecooled to 0° C.
  3. temperatureto warm to room temperature
  4. stirringstirred for approximately a further 40 hours when LCMS

Sources & evidence

ORD record
ord-ee5a5e8b3ecb4523b9fbb429b3a439ab
Source dataset
uspto-grants-2013_11
Patent number
US08575340B2

Reaction notes

Loading…