HCID 178470568, compound → HCID 178520455, compound

HRID 276811Notes

Reaction equation

HRID 276811 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>>[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

3

Reactant 2

HCID 178470568HCID 178470568, compoundHCID 178524287HCID 178524287, compound

Product 1

HCID 178520455HCID 178520455, compound

Procedure

A slurry of (E)-3-[(1,3-bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]benzoic acid (from part (a) of this example, 0.500 g) in anhydrous N,N-dimethylfonnamide (10 mL) was heated briefly to near reflux under nitrogen. N,N′-Carbonyldiimidazole (Aldrich, 0.213 g) was added to the pale yellow slurry, which thinned and turned orange as a gas evolved. Within minutes the slurry turned bright yellow and yellow solid precipitated. The mixture was stirred for 18 h, diluted with dichloromethane (30 mL), and filtered. The 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 (0.46 g). A mixture of this solid (0.45 g), nonaethylene glycol monomethyl ether, (from part (a) of example 10, 0.393 g) and anhydrous potassium carbonate (0.242 g) in acetonitrile (10 mL) was stirred at reflux 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 chromatographed on silica gel. Elution with 10% methanolchloroform evaporation of solvents gave (E)-3-[1,3-bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]benzoic acid nonaethylene glycol methyl ether ester as a waxy white solid (0.262 g, 38%); 1H-NMR (DMSO-d6)6: 8.79 (s) and 8.43 (d, J=7.9), 8.11 (d, J=8.0), and 7.57 (m, each 1, C6H4), 4.50 (m, 2, CH2O), 3.99 (d,J=7.1, 2, CH2N), 3.83 (m, 4, CH2N and CH2O), 3.70-3.40 (m, 32, 16 CH2), 3.28 (s, 3, CH3), 2.1-1.6 and 1.4-1.0 (both m, 22, cyclohexyl CH2 and CH).

Workup

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

Sources & evidence

ORD record
ord-e2e2de1cf6ec48b6942cd8212f3ba0a3
Source dataset
uspto-grants-2002_03
Patent number
US06355646B1

Reaction notes

Loading…