HCID 178470568, compound → HCID 178520455, compound

HRID 276813Notes

Reaction equation

HRID 276813 reaction equation
[CH:1]1([CH2:7][N:8]2[C:16](=[O:17])[C:15]3[N:14]=[C:13]([C:18]4[CH:26]=[CH:25][CH:24]=[CH:23][C:19]=4C(O)=O)[NH:12][C:11]=3[N:10]([CH2:27][CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)[C:9]2=[O:34])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(OC(=O)C(Br)C(C1C=CC([C:48]2[NH:49][C:50]3N(CC4CCCCC4)C(=O)N(CC4CCCCC4)C(=O)[C:55]=3[N:56]=2)=CC=1)Br)C>CN(C)C=O.ClCCl>[CH:1]1([CH2:7][N:8]2[C:16](=[O:17])[C:15]3[N:14]=[C:13]([C:18]4[CH:19]=[CH:23][CH:24]=[C:25](/[CH:11]=[CH:15]/[C:16]([N:49]5[CH:50]=[CH:55][N:56]=[CH:48]5)=[O:17])[CH:26]=4)[NH:12][C:11]=3[N:10]([CH2:27][CH:28]3[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]3)[C:9]2=[O:34])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 2

HCID 178470568HCID 178470568, compoundHCID 178524287HCID 178524287, compound

Product 1

HCID 178520455HCID 178520455, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

A slurry of (E)-4-[(1,3-bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]benzoic acid (from part (a) of this example, 0.50 g) in anhydrous N,N-dimethylformamide (10 mL) was heated briefly to near reflux under nitrogen. N,N′-Carbonyldiimidazole (Aldrich, 0.211 g) was then added to the pale yellow slurry, which thinned and turned orange as a gas evolved. Within minutes the slurry turned a bright yellow and thickened as a yellow solid formed. The mixture was stirred for 18 h, diluted with dichloromethane (30 mL), and filtered. The bright yellow solid was washed with dichloromethane (30 mL), and dried at 40° C. to provide (E)-1,3-bis(cyclohexylmethyl)-8-[3-(2-(1H-imidazol-1-ylcarbonyl)vinyl)phenyl]-9H-purin-2,6(1H,3H)-dione as a yellow powder (0.32 g). A mixture of this sample (0.32 g), nonaethylene glycol monomethyl ether (from part (a) of example 10, 0.277 g) and anhydrous potassium carbonate (0.170 g) in acetonitrile (10 mL) was refluxed for 20 h. Chloroform (50 mL) was added and the solution was washed with 1N HCl, (20 mL). The organic layer was washed with brine, dried (magnesium sulfate), and eluted from a silica gel column with 10% methanol-chloroform. Evaporation of solvents left yellow waxy solid which was reprecipitated from ethyl acetate-hexanes. The yellow waxy solid precipitate was filtered and dried to (E)-4-[1,3-bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]benzoic acid nonaethylene glycol methyl ether ester (0.355 g, 65%); 1H-NMR (DMSO-d6) δ: 8.24 (d, J=8.4, 2,2 CH), 8.06 (d, I=8.6, 2, 2 CH), 4.40 (m, 2, CH2O), 3.90 (d, J=7.3, 2, CH2N), 3.75 (m, 4, CH2N and CH2O), 3.70-3.40 (m, 32, 16 CH2), 3.19 (s, 3, CH3), 2.1-1.6 and 1.4-1.0 (m, 22, cyclohexyl CH2 and CH).

Workup

  1. temperatureto near reflux under nitrogen
  2. waitWithin minutes the slurry turned
  3. customa bright yellow and thickened as a yellow solid formed
  4. filtrationfiltered
  5. washThe bright yellow solid was washed with dichloromethane (30 mL)
  6. customdried at 40° C.

Sources & evidence

ORD record
ord-b057d1819102493c8a666d0c31a6606f
Source dataset
uspto-grants-2002_03
Patent number
US06355646B1

Reaction notes

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