Water → 7-[2-(t-butyldimethylsilanyloxy)ethyl]-4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2-amine

HRID 2239780Notes

Reaction equation

HRID 2239780 reaction equation
[H-].[Na+].[Cl:3][C:4]1[C:5]2[CH:13]=[CH:12][NH:11][C:6]=2[N:7]=[C:8]([NH2:10])[N:9]=1.Br[CH2:15][CH2:16][O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19].O>CN(C=O)C>[Si:18]([O:17][CH2:16][CH2:15][N:11]1[C:6]2[N:7]=[C:8]([NH2:10])[N:9]=[C:4]([Cl:3])[C:5]=2[CH:13]=[CH:12]1)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 53244134-chloro-7H-pyrrolo(2,3-d)pyrimidin-2-amine

Product 1

HCID 866234637-[2-(t-butyldimethylsilanyloxy)ethyl]-4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of NaH (0.618 g, 15.45 mmol) in anhydrous DMF (15 mL) at 0° C. is added slowly a solution of 4-chloro-7H-pyrrolo[2,3-d]pyrimidin-2-amine (2 g, 11.86 mmol) in 5 mL of anhydrous DMF. The mixture is stirred at this temperature under N2 for 15 min, then (2-bromoethoxy)-t-butyldimethylsilane (4.0 mL, 18.64 mmol) is added at 0° C. The mixture is stirred at RT overnight. The reaction mixture is poured into water and extracted with ethyl acetate (EtOAc; 4×). The organic layer is dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated in vacuo. The crude product is purified by flash cromatography using EtOAc/cyclohexane (1/1) as eluent to yield 7-[2-(t-butyldimethylsilanyloxy)ethyl]-4-chloro-7H-pyrrolo [2,3-d]pyrimidin-2-amine as white needles: LC/MS (M+1=327). 1H NMR (CDCl3, 400 MHz) δ-0.08 (s, 6H), 0.84 (s, 9H), 3.88 (t, 2H, J=5.2 Hz), 4.17 (t, 2H, J=5.2 Hz), 4.89 (s, 2H, NH2), 6.35 (d, 1H, J=3.6 Hz), 6.96 (d, 1H, J=16 Hz).

Workup

  1. stirringThe mixture is stirred at RT overnight
  2. extractionextracted with ethyl acetate (EtOAc; 4×)
  3. dry with materialThe organic layer is dried over anhydrous magnesium sulfate (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified by flash cromatography

Sources & evidence

ORD record
ord-f83cfbfed95f45278d51176d6ff9014b
Source dataset
uspto-grants-2010_05
Patent number
US07723343B2

Reaction notes

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