Diisopropylethylamine → 4-[6-((2S)-2-Benzyloxycarbonylamino-2-tert-butoxycarbonyl-ethylamino)-purin-9-yl]-butyric acid ethyl ester

HRID 854247Notes

Reaction equation

HRID 854247 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH2:6][CH2:7][N:8]1[CH:16]=[N:15][C:14]2[C:9]1=[N:10][CH:11]=[N:12][C:13]=2Cl)[CH3:2].C(N(CC)C(C)C)(C)C.[C:28]([O:32][C:33](=[O:48])[C@@H:34]([NH:37][C:38]([O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:39])[CH2:35][NH2:36])([CH3:31])([CH3:30])[CH3:29]>CN(C)C=O>[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH2:6][CH2:7][N:8]1[CH:16]=[N:15][C:14]2[C:9]1=[N:10][CH:11]=[N:12][C:13]=2[NH:36][CH2:35][C@H:34]([NH:37][C:38]([O:40][CH2:41][C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1)=[O:39])[C:33]([O:32][C:28]([CH3:30])([CH3:31])[CH3:29])=[O:48])[CH3:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 10803731(S)-tert-Butyl 3-amino-2-(((benzyloxy)carbonyl)amino)propanoateHCID 155472644-(6-Chloro-purin-9-yl)-butyric acid ethyl ester

Product 1

HCID 155472654-[6-((2S)-2-Benzyloxycarbonylamino-2-tert-butoxycarbonyl-ethylamino)-purin-9-yl]-butyric acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

1 g (3.72 mmol) of 4-(6-chloro-purin-9-yl)-butyric acid ethyl ester was dissolved in dimethylformamide (3 ml) and 2.6 ml (14.9 mmol) of N,N-diisopropylethylamine was added. 1.09 g (3.72 mmol) of (2S)-3-amino-2-benzyloxycarbonylamino-propionic acid tert-butyl ester and dimethylformamide (2 ml) were added. The reaction was stirred at 80° C. for 2 days. The solvent was removed in vacuo, the residue was dissolved in dichloromethane and the solution was washed three times with 10% aqueous citric acid solution and three times with water. The organic phase was dried with sodium sulfate, filtered and the solvent was removed in vacuo. Residual amounts of 4-(6-chloro-purin-9-yl)-butyric acid ethyl ester were removed as follows: the residue was dissolved in tetrahydrofuran and 2 g of a macroporous aminomethyl polystyrene resin was added. The suspension was heated at 60° C. for 5 hours, then stirred gently at room temperature for 16 hours. The resin was filtered off, washed with tetrahydrofuran, and the combined organic phase was dried in vacuo. Yield: 908 mg.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in dichloromethane
  3. washthe solution was washed three times with 10% aqueous citric acid solution and three times with water
  4. dry with materialThe organic phase was dried with sodium sulfate
  5. filtrationfiltered
  6. customthe solvent was removed in vacuo
  7. customResidual amounts of 4-(6-chloro-purin-9-yl)-butyric acid ethyl ester were removed
  8. dissolutionthe residue was dissolved in tetrahydrofuran
  9. addition2 g of a macroporous aminomethyl polystyrene resin was added
  10. temperatureThe suspension was heated at 60° C. for 5 hours
  11. stirringstirred gently at room temperature for 16 hours
  12. filtrationThe resin was filtered off
  13. washwashed with tetrahydrofuran
  14. customthe combined organic phase was dried in vacuo

Sources & evidence

ORD record
ord-7b468c637b0a47fc95c924a592f0b934
Source dataset
uspto-grants-2007_08
Patent number
US07259159B2

Reaction notes

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