6-Chloro-2-iodo-9-(tetrahydro-2H-pyran-2-yl)-9H-purine → N-(4-(Dipropylphosphoryl)phenyl)-2-iodo-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

HRID 2041919Notes

Reaction equation

HRID 2041919 reaction equation
CC(C)([O-])C.[K+].[CH2:7]([P:10]([C:15]1[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=1)([CH2:12][CH2:13][CH3:14])=[O:11])[CH2:8][CH3:9].Cl[C:23]1[N:31]=[C:30]([I:32])[N:29]=[C:28]2[C:24]=1[N:25]=[CH:26][N:27]2[CH:33]1[CH2:38][CH2:37][CH2:36][CH2:35][O:34]1>C1COCC1>[CH2:7]([P:10]([C:15]1[CH:16]=[CH:17][C:18]([NH:21][C:23]2[N:31]=[C:30]([I:32])[N:29]=[C:28]3[C:24]=2[N:25]=[CH:26][N:27]3[CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)=[CH:19][CH:20]=1)([CH2:12][CH2:13][CH3:14])=[O:11])[CH2:8][CH3:9]

Participants

5

Reactant 3

HCID 112107406-Chloro-2-iodo-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 23665647Potassium tert-butoxideHCID 599945404-(Dipropylphosphoryl)aniline

Product 1

HCID 86631259N-(4-(Dipropylphosphoryl)phenyl)-2-iodo-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

Potassium tert-Butoxide (0.19 g, 1.65 mmol) was suspended in 4.5 mL anhydrous THF under nitrogen and cooled to −10° C. in an ice-salt bath. 4-(Dipropylphosphoryl)benzenamine (0.12 g, 0.55 mmol) was added to the suspension and the mixture was stirred at −10° C. for 30 min. 6-Chloro-2-iodo-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (Tetrahedron 2002, 58, 7911-7923, 0.18 mg, 0.5 mmol) was then added to the reaction mixture and the content was warmed to room temperature and stirred over night. The reaction mixture was cooled to 0° C., and quenched by the addition of 0.1 N HCl (˜500 mL). The mixture was concentrated on a rotavapor. The residue was partitioned between ethyl acetate (10 mL)/water (4 mL), organic layer was separated and washed with 0.1 N HCl (4×4 mL), saturated NaHCO3 (4 mL), brine (4 mL), and dried over Na2SO4. The final product was obtained by flash column chromatography on silica gel (7.5% MeOH/DCM).

Workup

  1. temperaturethe content was warmed to room temperature
  2. stirringstirred over night
  3. temperatureThe reaction mixture was cooled to 0° C.
  4. customquenched by the addition of 0.1 N HCl (˜500 mL)
  5. concentrationThe mixture was concentrated on a rotavapor
  6. customThe residue was partitioned between ethyl acetate (10 mL)/water (4 mL), organic layer
  7. customwas separated
  8. washwashed with 0.1 N HCl (4×4 mL), saturated NaHCO3 (4 mL), brine (4 mL)
  9. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-b0a2a3b6468542f38f2c2c43d5b24520
Source dataset
uspto-grants-2013_11
Patent number
US08586566B2

Reaction notes

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