Sodium Iodide → 2-{[(1S)-1-Methylbutyl]oxy}-8-(methyloxy)-9-[4-(tetrahydro-2H-pyran-4-ylamino)butyl]-9H-purin-6-amine

HRID 2036359Notes

Reaction equation

HRID 2036359 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:14]([O:15][CH3:16])=[N:13][C:12]2[C:7]1=[N:8][C:9]([O:18][C@@H:19]([CH3:23])[CH2:20][CH2:21][CH3:22])=[N:10][C:11]=2[NH2:17].C(N(CC)C(C)C)(C)C.[I-].[Na+].[O:35]1[CH2:40][CH2:39][CH:38]([NH2:41])[CH2:37][CH2:36]1>C(#N)C.CS(C)=O>[CH3:23][C@H:19]([O:18][C:9]1[N:8]=[C:7]2[C:12]([N:13]=[C:14]([O:15][CH3:16])[N:6]2[CH2:5][CH2:4][CH2:3][CH2:2][NH:41][CH:38]2[CH2:39][CH2:40][O:35][CH2:36][CH2:37]2)=[C:11]([NH2:17])[N:10]=1)[CH2:20][CH2:21][CH3:22]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 4192234-AminotetrahydropyranHCID 582909339-(4-Chlorobutyl)-2-{[(1S)-1-methylbutyl]oxy}-8-(methyloxy)-9H-purin-6-amine

Product 1

HCID 582909342-{[(1S)-1-Methylbutyl]oxy}-8-(methyloxy)-9-[4-(tetrahydro-2H-pyran-4-ylamino)butyl]-9H-purin-6-amineYield 36.4%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

9-(4-Chlorobutyl)-2-{[(1S)-1-methylbutyl]oxy}-8-(methyloxy)-9H-purin-6-amine (70 mg, 0.205 mmol) was mixed with N,N-diisopropylethylamine (0.179 ml, 1.024 mmol), sodium iodide (30.7 mg, 0.205 mmol) and tetrahydro-2H-pyran-4-amine (62.1 mg, 0.614 mmol) in acetonitrile (1.5 ml) and heated at 70° C. under nitrogen overnight and then left at ambient temperature over the weekend. The acetonitrile was evaporated under nitrogen and the residue partitioned between aqueous sodium bicarbonate and dichloromethane. The aqueous phase was re-extracted with dichloromethane and the combined organic extracts were passed through a hydrophobic frit and evaporated under nitrogen to give an amber oil. This material was dissolved in 1:1 DMSO:MeOH (2×1 ml) and purified in two injections by Mass Directed AutoPrep (Method A). Product containing fractions were combined evaporated under nitrogen in a blowdown unit to give the title compound as a colourless oil (30.35 mg).

Workup

  1. waitleft at ambient temperature over the weekend
  2. customThe acetonitrile was evaporated under nitrogen
  3. customthe residue partitioned between aqueous sodium bicarbonate and dichloromethane
  4. extractionThe aqueous phase was re-extracted with dichloromethane
  5. customevaporated under nitrogen
  6. customto give an amber oil
  7. customMeOH (2×1 ml) and purified in two injections by Mass Directed AutoPrep (Method A)
  8. additionProduct containing fractions
  9. customwere combined evaporated under nitrogen in a blowdown unit

Sources & evidence

ORD record
ord-97ecf7c386944a34b51a83494d36858a
Source dataset
uspto-grants-2013_11
Patent number
US08575181B2

Reaction notes

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