Trifluoroacetic acid → HCID 178474133, compound

HRID 720614Notes

Reaction equation

HRID 720614 reaction equation
[F:1][C:2]1[CH:55]=[CH:54][CH:53]=[CH:52][C:3]=1[CH2:4][N:5]1[C:13](=[O:14])[C:12]2[NH:11][C:10]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23](=[O:25])[CH3:24])=[CH:18][CH:17]=3)=[N:9][C:8]=2[N:7]([CH2:26][C:27]2[N:31]=[CH:30][N:29](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:28]=2)[C:6]1=[O:51].FC(F)(F)C(O)=O.C([SiH](CC)CC)C>ClCCl>[F:1][C:2]1[CH:55]=[CH:54][CH:53]=[CH:52][C:3]=1[CH2:4][N:5]1[C:13](=[O:14])[C:12]2[NH:11][C:10]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23](=[O:25])[CH3:24])=[CH:18][CH:17]=3)=[N:9][C:8]=2[N:7]([CH2:26][C:27]2[N:31]=[CH:30][NH:29][N:28]=2)[C:6]1=[O:51]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 58739237HCID 58739237, compound

Product 1

HCID 178474133HCID 178474133, compoundYield 40.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A suspension of N-{4-[1-(2-fluoro-benzyl)-2,6-dioxo-3-(1-trityl-1H-[1,2,4]triazol-3-ylmethyl)-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-acetamide (47 mg, 0.06 mmol) in dichloromethane (1.0 mL) at 25° C. was treated with trifluoroacetic acid (1.0 mL). The reaction was stirred at 25° C. for 1 h. At this time, the reaction was treated with triethylsilane (0.01 mL, 0.06 mmol) and then was concentrated in vacuo. The resulting residue was purified by HPLC (15–60% acetonitrile/water (0.075% trifluoroacetic acid in both solvents) over 40 min). Fractions with the desired product were combined and concentrated in vacuo. The resulting residue was diluted with dichloromethane (100 mL) and was washed with a saturated aqueous sodium bicarbonate solution (25 mL). The aqueous layer was re-extracted with dichloromethane (1×50 mL). The combined organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting solid was dried in vacuo for 24 h to afford N-{4-[1-(2-fluoro-benzyl)-2,6-dioxo-3-(1H-[1,2,4]triazol-3-ylmethyl)-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-acetamide (12 mg, 26%) as a white solid: LR-MS for C24H21FN8O3 (M+H)+ at m/z=489.

Workup

  1. concentrationwas concentrated in vacuo
  2. customThe resulting residue was purified by HPLC (15–60% acetonitrile/water (0.075% trifluoroacetic acid in both solvents) over 40 min)
  3. concentrationconcentrated in vacuo
  4. additionThe resulting residue was diluted with dichloromethane (100 mL)
  5. washwas washed with a saturated aqueous sodium bicarbonate solution (25 mL)
  6. extractionThe aqueous layer was re-extracted with dichloromethane (1×50 mL)
  7. dry with materialThe combined organics were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resulting solid was dried in vacuo for 24 h

Sources & evidence

ORD record
ord-13baa610df254e9384de79e89cf6cf69
Source dataset
uspto-grants-2006_11
Patent number
US07135475B2

Reaction notes

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