Triphenylphosphine → HCID 86590835, compound

HRID 720669Notes

Reaction equation

HRID 720669 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([NH:10][C:11]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:5][C:6]=1[C:7](O)=[O:8].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.ClN1C(=O)CCC1=O.[CH:57]1([CH2:60][N:61]2[C:69]3[N:68]=[C:67]([CH2:70][C:71]4[CH:76]=[CH:75][C:74]([NH:77][CH3:78])=[CH:73][CH:72]=4)[NH:66][C:65]=3[C:64](=[O:79])[N:63]([CH2:80][C:81]3[CH:86]=[CH:85][CH:84]=[CH:83][C:82]=3[F:87])[C:62]2=[O:88])[CH2:59][CH2:58]1>ClCCl>[CH:57]1([CH2:60][N:61]2[C:69]3[N:68]=[C:67]([CH2:70][C:71]4[CH:72]=[CH:73][C:74]([N:77]([CH3:78])[C:7]([C:6]5[S:5][C:4]([NH:10][C:11]([C:24]6[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=6)([C:12]6[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=6)[C:18]6[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=6)=[N:3][C:2]=5[CH3:1])=[O:8])=[CH:75][CH:76]=4)[NH:66][C:65]=3[C:64](=[O:79])[N:63]([CH2:80][C:81]3[CH:86]=[CH:85][CH:84]=[CH:83][C:82]=3[F:87])[C:62]2=[O:88])[CH2:59][CH2:58]1

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 31398Chlorosuccinimide2×HCID 218916913-Cyclopropylmethyl-8-[4-(methylamino)-benzyl]-1-(2-fluorobenzyl)-3,7-dihydropurine-2,6-dioneHCID 21891719HCID 21891719, compound

Product 1

HCID 86590835HCID 86590835, compoundYield 83.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

A mixture of 4-methyl-2-(trityl-amino)-thiazole-5-carboxylic acid (46 mg, 0.11 mmol) in dichloromethane (1.0 mL) at 25° C. was treated with triphenylphosphine (36 mg, 0.14 mmol). The reaction was cooled to 0° C. and was treated with N-chlorosuccinimide (18 mg, 0.14 mmol). This mixture was stirred at 0° C. for 30 min and then was warmed to 25° C. for 20 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 (100 mg, 0.23 mmol) and dichloromethane (2.5 mL). The reaction was stirred at 25° C. for 18 h. At this time, the reaction was treated with another portion of triphenylphosphine (36 mg, 0.14 mmol) and N-chlorosuccinimide (18 mg, 0.14 mmol). The reaction was stirred at 25° C. for 1 h. At this time, the reaction was diluted with dichloromethane (100 mL) and then washed with a saturated aqueous sodium bicarbonate solution (1×25 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 80:20 ethyl acetate/petroleum ether) afforded 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 (75.1 mg, 80.0%). The product was used without further purification or characterization.

Workup

  1. temperaturewas warmed to 25° C. for 20 min
  2. stirringThe reaction was stirred at 25° C. for 18 h
  3. stirringThe reaction was stirred at 25° C. for 1 h
  4. washwashed with a saturated aqueous sodium bicarbonate solution (1×25 mL)
  5. dry with materialThe organics were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f9a344e171694f3b8961744accab2c78
Source dataset
uspto-grants-2006_11
Patent number
US07135475B2

Reaction notes

Loading…