Triethylamine → [1,2,3]thiadiazole-4-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-methyl-amide

HRID 720675

Reaktionsgleichung

Reaktionsgleichung von HRID 720675
[S:1]1[CH:5]=[C:4]([C:6]([OH:8])=O)[N:3]=[N:2]1.ClN1C(=O)CCC1=O.[CH:17]1([CH2:20][N:21]2[C:29]3[N:28]=[C:27]([CH2:30][C:31]4[CH:36]=[CH:35][C:34]([NH:37][CH3:38])=[CH:33][CH:32]=4)[NH:26][C:25]=3[C:24](=[O:39])[N:23]([CH2:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=3[F:47])[C:22]2=[O:48])[CH2:19][CH2:18]1.C(N(CC)CC)C>ClCCl>[CH:17]1([CH2:20][N:21]2[C:29]3[N:28]=[C:27]([CH2:30][C:31]4[CH:32]=[CH:33][C:34]([N:37]([CH3:38])[C:6]([C:4]5[N:3]=[N:2][S:1][CH:5]=5)=[O:8])=[CH:35][CH:36]=4)[NH:26][C:25]=3[C:24](=[O:39])[N:23]([CH2:40][C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=3[F:47])[C:22]2=[O:48])[CH2:19][CH2:18]1

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 31398ChlorosuccinimideHCID 3514181,2,3-Thiadiazole-4-carboxylic acidHCID 218916913-Cyclopropylmethyl-8-[4-(methylamino)-benzyl]-1-(2-fluorobenzyl)-3,7-dihydropurine-2,6-dione

Produkt 1

HCID 58739256[1,2,3]thiadiazole-4-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-methyl-amideAusbeute 26 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A mixture of [1,2,3]thiadiazole-4-carboxylic acid (29 mg, 0.30 mmol) in dichloromethane (6 mL) at 25° C. was treated with triphenylphosphine-polystyrene 100–200 mesh (372 mg, 0.46 mmol). This mixture was cooled to 0° C. and then treated with N-chlorosuccinimide (49 mg, 0.37 mmol). This mixture was stirred at 0° C. for 15 min and at 25° C. for 15 min. At this time, the reaction was treated with 3-cyclopropylmethyl-1-(2-fluoro-benzyl)-8-(4-methylamino-benzyl)-3,7-dihydro-purine-2,6-dione (55 mg, 0.12mmol) and triethylamine (96 μL, 0.69 mmol). The reaction was then stirred at 25° C. for 3 days. At this time, the reaction was filtered to remove solids and rinsed with dichloromethane. The filtrate was washed with a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution. The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 1:99 methanol/dichloromethane) afforded [1,2,3]thiadiazole-4-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-methyl-amide (17 mg, 24.7%): LR-MS for C27H24FN7O3S (M+H)+ at m/z=546.

Aufarbeitung

  1. stirringThe reaction was then stirred at 25° C. for 3 days
  2. filtrationAt this time, the reaction was filtered
  3. customto remove solids
  4. washrinsed with dichloromethane
  5. washThe filtrate was washed with a saturated aqueous sodium bicarbonate solution
  6. dry with materialThe organics were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-e121bc531c7b45bbab376c57d5883004
Quelldatensatz
uspto-grants-2006_11
Patentnummer
US07135475B2

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