Triphenylphosphine → HCID 58739260, compound

HRID 720612Notes

Reaction equation

HRID 720612 reaction equation
[C:1]([N:20]1[CH:24]=[N:23][C:22]([CH2:25]O)=[N:21]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O.[C:58]([NH:61][C:62]1[CH:67]=[CH:66][C:65]([CH2:68][C:69]([NH:71][C:72]2[C:73](=[O:88])[N:74]([CH2:80][C:81]3[CH:86]=[CH:85][CH:84]=[CH:83][C:82]=3[F:87])[C:75](=[O:79])[NH:76][C:77]=2[NH2:78])=[O:70])=[CH:64][CH:63]=1)(=[O:60])[CH3:59]>O1CCCC1>[C:58]([NH:61][C:62]1[CH:63]=[CH:64][C:65]([CH2:68][C:69]([NH:71][C:72]2[C:73](=[O:88])[N:74]([CH2:80][C:81]3[CH:86]=[CH:85][CH:84]=[CH:83][C:82]=3[F:87])[C:75](=[O:79])[N:76]([CH2:25][C:22]3[N:23]=[CH:24][N:20]([C:1]([C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)([C:8]4[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=4)[C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[N:21]=3)[C:77]=2[NH2:78])=[O:70])=[CH:66][CH:67]=1)(=[O:60])[CH3:59]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 13471694(1-trityl-1H-1,2,4-triazol-3-yl)methanolHCID 218917492-(4-acetamidophenyl)-N-(6-amino-3-(2-fluorobenzyl)-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)acetamide

Product 1

HCID 58739260HCID 58739260, compoundYield 15.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of (1-trityl-1H-[1,2,4]triazol-3-yl)-methanol (320 mg, 0.47 mmol) and triphenylphosphine (136 mg, 0.47 mmol) in tetrahydrofuran (9.4 mL) cooled to 0° C. was treated with diethylazodicarboxylate (0.82 mL, 0.47 mmol). This solution was warmed to 25° C. for 5 min and then was re-cooled to 0° C. where it was stirred for an additional 10 min. At this time, the reaction was treated with 2-(4-acetylamino-phenyl)-N-[6-amino-3-(2-fluoro-benzyl)-2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-yl]-acetamide (200 mg, 0.47 mmol). The reaction was then allowed to slowly warm to 25° C. The resulting solids were removed by filtration. The filtrate was diluted with ethyl acetate, washed with water and a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh) afforded 2-(4-acetylamino-phenyl)-N-[6-amino-3-(2-fluoro-benzyl)-2,4-dioxo-1-(1-trityl-1H-[1,2,4]triazol-3-ylmethyl)-1,2,3,4-tetrahydro-pyrimidin-5-yl]-acetamide (55 mg, 15.6%) as a yellow foam: LR-APCI for C43H37FN8O4 (M+H)+at m/z=749.

Workup

  1. temperatureThis solution was warmed to 25° C. for 5 min
  2. temperaturewas re-cooled to 0° C. where it
  3. temperatureto slowly warm to 25° C
  4. customThe resulting solids were removed by filtration
  5. additionThe filtrate was diluted with ethyl acetate
  6. washwashed with water
  7. dry with materiala saturated aqueous sodium chloride solution, dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e43dea8f3ba84cf7b0e5ce02c3a1870a
Source dataset
uspto-grants-2006_11
Patent number
US07135475B2

Reaction notes

Loading…