Triethylamine → (S)-9-(5-chloropentyl)-8-methoxy-2-(pentan-2-yloxy)-9H-purin-6-amine

HRID 2367965Notes

Reaction equation

HRID 2367965 reaction equation
FC(F)(F)C(O)=O.[CH3:8][C@H:9]([O:13][C:14]1[N:22]=[C:21]2[C:17]([N:18]=[C:19]([O:23][CH3:24])[NH:20]2)=[C:16]([NH2:25])[N:15]=1)[CH2:10][CH2:11][CH3:12].C(=O)([O-])[O-].[K+].[K+].Br[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][Cl:38].C(N(CC)CC)C>CN(C=O)C.O.[Cl-].[Na+].O>[Cl:38][CH2:37][CH2:36][CH2:35][CH2:34][CH2:33][N:20]1[C:19]([O:23][CH3:24])=[N:18][C:17]2[C:21]1=[N:22][C:14]([O:13][C@@H:9]([CH3:8])[CH2:10][CH2:11][CH3:12])=[N:15][C:16]=2[NH2:25]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 960701-Bromo-5-chloropentaneHCID 178448286HCID 178448286, compound2×

Product 1

HCID 59252634(S)-9-(5-chloropentyl)-8-methoxy-2-(pentan-2-yloxy)-9H-purin-6-amine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
20 °C

Procedure

2-{[(1S)-1-Methylbutyl]oxy}-8-(methyloxy)-9H-purin-6-amine, trifluoroacetate salt (600 mg, 1.642 mmol) (for example, as prepared for Intermediate 7) and potassium carbonate (567 mg, 4.11 mmol) were stirred at 60° C. in DMF (10 mL) for 1 hour under nitrogen. The reaction was cooled to room temperature when 1-bromo-5-chloropentane (commercially available, for example, from Aldrich) (0.216 mL, 1.642 mmol) and triethylamine (0.343 mL, 2.464 mmol) were added and the mixture stirred at 20° C. under nitrogen for 16 hours. The mixture was then diluted with water (10 mL) and brine (10 mL) and extracted with dichloromethane (2×10 mL). The combined organic extracts were evaporated and the residue dissolved in dichloromethane and purified by column chromatography using the Flashmaster II (70 g aminopropyl cartridge) with a 0-100% ethyl acetate in cyclohexane gradient over 40 minutes. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a yellow gum (430 mg).

Workup

  1. extractionextracted with dichloromethane (2×10 mL)
  2. customThe combined organic extracts were evaporated
  3. dissolutionthe residue dissolved in dichloromethane
  4. custompurified by column chromatography
  5. customover 40 minutes
  6. customevaporated in vacuo

Sources & evidence

ORD record
ord-acade3616bb84021b4c99fa94ed2d432
Source dataset
uspto-grants-2014_04
Patent number
US08703754B2

Reaction notes

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