Triphenylphosphine → 1-methyl-1H-pyrazole-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 720678Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 720678
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]([OH:9])=O)[CH:4]=[N:3]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.ClN1C(=O)CCC1=O.[CH:37]1([CH2:40][N:41]2[C:49]3[N:48]=[C:47]([CH2:50][C:51]4[CH:56]=[CH:55][C:54]([NH:57][CH3:58])=[CH:53][CH:52]=4)[NH:46][C:45]=3[C:44](=[O:59])[N:43]([CH2:60][C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][C:62]=3[F:67])[C:42]2=[O:68])[CH2:39][CH2:38]1>ClCCl>[CH:37]1([CH2:40][N:41]2[C:49]3[N:48]=[C:47]([CH2:50][C:51]4[CH:52]=[CH:53][C:54]([N:57]([CH3:58])[C:7]([C:5]5[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=5)=[O:9])=[CH:55][CH:56]=4)[NH:46][C:45]=3[C:44](=[O:59])[N:43]([CH2:60][C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][C:62]=3[F:67])[C:42]2=[O:68])[CH2:39][CH2:38]1

Komponenten

6

Edukt 4

HCID 11776TriphenylphosphineHCID 31398ChlorosuccinimideHCID 6431601-Methyl-1H-pyrazole-4-carboxylic acidHCID 218916913-Cyclopropylmethyl-8-[4-(methylamino)-benzyl]-1-(2-fluorobenzyl)-3,7-dihydropurine-2,6-dione

Produkt 1

HCID 587392401-methyl-1H-pyrazole-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 94,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A mixture of 1-methyl-1H-pyrazole-4-carboxylic acid (22 mg, 0.17 mmol) in dichloromethane (2.0 mL) at 25° C. was treated with triphenylphosphine (54 mg, 0.21 mmol). This mixture was cooled to 0° C. and then treated with N-chlorosuccinimide (28 mg, 0.21 mmol). This mixture was stirred at 0° C. for 30 min and then was warmed to 25° C. 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 (150 mg, 0.34 mmol). The reaction was then stirred at 25° C. for 2 days. At this time, the reaction was diluted with dichloromethane and then was washed with a saturated aqueous sodium bicarbonate solution. The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 3:97 methanol/dichloromethane) afforded 1-methyl-1H-pyrazole-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 (87 mg, 92.8%) as an off-white solid: LR-MS for C29H28FN7O3 (M+H)+ at m/z=542.

Aufarbeitung

  1. temperaturewas warmed to 25° C
  2. stirringThe reaction was then stirred at 25° C. for 2 days
  3. washwas washed with a saturated aqueous sodium bicarbonate solution
  4. dry with materialThe organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-87048f40720b446ca31637dad9b9b796
Quelldatensatz
uspto-grants-2006_11
Patentnummer
US07135475B2

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