Isopropyl iodide → N-(4-(Dipropylphosphoryl)phenyl)-2-isopropyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

HRID 655805Notes

Reaction equation

HRID 655805 reaction equation
[CH:1](I)([CH3:3])[CH3:2].[CH2:5]([P:8]([C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20]2[N:28]=[C:27](I)[N:26]=[C:25]3[C:21]=2[N:22]=[CH:23][N:24]3[CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][O:31]2)=[CH:15][CH:14]=1)([CH2:10][CH2:11][CH3:12])=[O:9])[CH2:6][CH3:7].CCOC(C)=O>CN(C=O)C.[Zn].Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:5]([P:8]([C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20]2[N:28]=[C:27]([CH:1]([CH3:3])[CH3:2])[N:26]=[C:25]3[C:21]=2[N:22]=[CH:23][N:24]3[CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][O:31]2)=[CH:15][CH:14]=1)([CH2:10][CH2:11][CH3:12])=[O:9])[CH2:6][CH3:7]

Participants

7

Reactant 3

HCID 6362Isopropyl iodideHCID 8857Ethyl AcetateHCID 86631259N-(4-(Dipropylphosphoryl)phenyl)-2-iodo-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Product 1

HCID 68928723N-(4-(Dipropylphosphoryl)phenyl)-2-isopropyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine

Reagents, catalysts & solvents 3

HCID 23994ZincCatalyst2×HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

To a oven-dried 10 mL round bottom flask was transferred under Ar 2.88 mL Rieke Zinc (0.14 g Zn, 2.2 mmol, 5 g/100 mL THF) using a 12 gauge needle. Then isopropyl iodide (200 □L, 2 mmol) was added via syringe. The solution turned warm and the content was stirred at rt for 3 h. In a separate flask (25 mL) was dissolved N-(4-(dipropylphosphoryl)phenyl)-2-iodo-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (0.28 g, 0.5 mmol) and PdCl2(PPh3)2 (0.035 g, 0.05 mmol) in 4.0 mL dry DMF. The Zinc reagent was transferred to the reaction via a syringe. The reaction mixture was stirred at rt overnight. 20 mL EtOAc/20 mL water was added to the reaction mixture and the content was filtered through Celite, washed with 1% MeOH/EtOAc (30 mL). The organic layer was separated and washed with water, brine, and dried Na2SO4. The final product was purified on silica gel (4-7.5% MeOH/DCM).

Workup

  1. temperatureThe solution turned warm
  2. stirringThe reaction mixture was stirred at rt overnight
  3. filtrationthe content was filtered through Celite
  4. washwashed with 1% MeOH/EtOAc (30 mL)
  5. customThe organic layer was separated
  6. washwashed with water, brine, and dried Na2SO4
  7. customThe final product was purified on silica gel (4-7.5% MeOH/DCM)

Sources & evidence

ORD record
ord-ea144ef3e8094aad989927042237e38e
Source dataset
uspto-grants-2011_12
Patent number
US08071609B2

Reaction notes

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