Trifluoroacetic acid → N-[4-(2-Amino-9-(3-azidopropyl)-purine-6-yloxymethyl)-benzyl]-2,2,2-trifluoro-acetamide

HRID 1695086Notes

Reaction equation

HRID 1695086 reaction equation
[F:1][C:2]([F:16])([F:15])[C:3]([NH:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][OH:14])=[CH:9][CH:8]=1)=[O:4].[H-].[Na+].[N:19]([CH2:22][CH2:23][CH2:24][N:25]1[CH:33]=[N:32][C:31]2[C:26]1=[N:27][C:28]([NH2:35])=[N:29][C:30]=2Cl)=[N+:20]=[N-:21].FC(F)(F)C(O)=O>CC(N(C)C)=O.O>[NH2:35][C:28]1[N:27]=[C:26]2[C:31]([N:32]=[CH:33][N:25]2[CH2:24][CH2:23][CH2:22][N:19]=[N+:20]=[N-:21])=[C:30]([O:14][CH2:13][C:10]2[CH:11]=[CH:12][C:7]([CH2:6][NH:5][C:3](=[O:4])[C:2]([F:15])([F:16])[F:1])=[CH:8][CH:9]=2)[N:29]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 24758Sodium hydrideHCID 15852209N-(4-Hydroxymethylbenzyl)trifluoroacetamideHCID 86067829N9-(3-Azidopropyl)-2-amino-6-chloropurine

Product 1

HCID 58989129N-[4-(2-Amino-9-(3-azidopropyl)-purine-6-yloxymethyl)-benzyl]-2,2,2-trifluoro-acetamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
90 °C

Procedure

2,2,2-Trifluoro-N-(4-hydroxymethyl-benzyl)-acetamide (138 mg, 0.59 mmol) is dissolved in 3 mL dry dimethylacetamide under argon atmosphere, and (31 mg, 1.31 mmol) NaH is added. N9-(3-Azidopropyl)-2-amino-6-chloropurine (22, 100 mg, 0.39 mmol) is added and the solution heated to 90° C. for 16 h. After cooling to room temperature, the mixture is poured into 80 mL of water and the pH is adjusted to 6 with trifluoroacetic acid. The aqueous phase is extracted with CH2Cl2 and ethyl acetate. The organic phases are washed with water and brine, dried over MgSO4 and the solvent is evaporated. The crude product is dissolved in methanol, adsorbed on SiO2 (150 mg) and purified by flash column chromatography with dichloromethane:methanol (95:5). Yield: 151 mg (0.0336 mmol, 85%). 1H-NMR (400 MHz, DMSO-d6): δ=10.00 (t, J=5.8, 1H, CF3CONH), 7.90 (s, 1H, H-8), 7.49, (d, J=8.1, 2H, ArH), 7.28 (d, J=8.1, 2H, ArH), 6.47 (s br, 2H, NH2), 5.46 (s, 2H, OCH2), 4.38 (d, J=5.8, 2H, CH2NH), 4.06 (t, J=6.5, 2H, CH2), 3.36 (t, J=6.5, 2H, CH2), 2.00 (m, 2H, CH2) ppm. MS (ESI) m/z 450.0 [M+H]+.

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionThe aqueous phase is extracted with CH2Cl2 and ethyl acetate
  3. washThe organic phases are washed with water and brine
  4. dry with materialdried over MgSO4
  5. customthe solvent is evaporated
  6. dissolutionThe crude product is dissolved in methanol
  7. custompurified by flash column chromatography with dichloromethane:methanol (95:5)

Sources & evidence

ORD record
ord-0311eb9be0694e11a1c56e888b4c833f
Source dataset
uspto-grants-2012_04
Patent number
US08163479B2

Reaction notes

Loading…