Trifluoroacetic acid → HCID 86590836, Verbindung

HRID 720670Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 720670
[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

Komponenten

5

Edukt 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 86590835HCID 86590835, Verbindung

Produkt 1

HCID 86590836HCID 86590836, VerbindungAusbeute 5,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-eca7dd3bcf624ea18b6e7f9660698d5e
Quelldatensatz
uspto-grants-2006_11
Patentnummer
US07135475B2

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