Trifluoroacetic acid → HCID 86590836, compound

HRID 720670Notes

Reaction equation

HRID 720670 reaction equation
[CH:1]1([CH2:4][N:5]2[C:13]3[N:12]=[C:11]([CH2:14][C:15]4[CH:20]=[CH:19][C:18]([N:21]([CH3:50])[C:22]([C:24]5[S:28][C:27]([NH:29]C(C6C=CC=CC=6)(C6C=CC=CC=6)C6C=CC=CC=6)=[N:26][C:25]=5[CH3:49])=[O:23])=[CH:17][CH:16]=4)[NH:10][C:9]=3[C:8](=[O:51])[N:7]([CH2:52][C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=3[F:59])[C:6]2=[O:60])[CH2:3][CH2:2]1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C>ClCCl>[CH:1]1([CH2:4][N:5]2[C:13]3[N:12]=[C:11]([CH2:14][C:15]4[CH:16]=[CH:17][C:18]([N:21]([CH3:50])[C:22]([C:24]5[S:28][C:27]([NH2:29])=[N:26][C:25]=5[CH3:49])=[O:23])=[CH:19][CH:20]=4)[NH:10][C:9]=3[C:8](=[O:51])[N:7]([CH2:52][C:53]3[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=3[F:59])[C:6]2=[O:60])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 86590835HCID 86590835, compound

Product 1

HCID 86590836HCID 86590836, compoundYield 5.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 4-methyl-2-(trityl-amino)-thiazole-5-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-methyl-amide (74.0 mg, 0.09 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 (16 μL, 0.10 mmol). The reaction 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 2-amino-4-methyl-thiazole-5-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-methyl-amide (3.0 mg, 5.8%) as a white solid: (ES)+-HRMS m/e calcd for C29H28N7O3SF (M+H)+ 574.2031, found 574.2035.

Workup

  1. concentrationThe reaction was 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-eca7dd3bcf624ea18b6e7f9660698d5e
Source dataset
uspto-grants-2006_11
Patent number
US07135475B2

Reaction notes

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