Triethylamine → 1,3-Bis(cyclohexylmethyl)-8-[4-(2,5,8,11,14,17,20,23,26,29-decaoxatriacont-1-yl)phenyl]-3,7-dihydro-1h-purine-2,6-dione

HRID 396267Notes

Reaction equation

HRID 396267 reaction equation
C(C1C=CC(C[CH2:9][O:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][O:22][CH2:23][CH2:24][O:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][O:31][CH2:32][CH2:33]OCCO)=CC=1)(O)=O.[C:40](Cl)(=[O:44])[C:41](Cl)=[O:42].C(N([CH2:51][CH3:52])CC)C.[CH:53]1([CH2:59][N:60]2[C:67]([NH2:68])=[C:66]([NH2:69])[C:64](=[O:65])[N:63]([CH2:70][CH:71]3[CH2:76][CH2:75][CH2:74][CH2:73][CH2:72]3)[C:61]2=[O:62])[CH2:58][CH2:57][CH2:56][CH2:55][CH2:54]1>ClCCl.CN(C)C=O>[CH:71]1([CH2:70][N:63]2[C:64](=[O:65])[C:66]3[NH:69][C:59]([C:53]4[CH:58]=[CH:57][C:51]([CH2:52][O:42][CH2:41][CH2:40][O:44][CH2:33][CH2:32][O:31][CH2:30][CH2:29][O:28][CH2:27][CH2:26][O:25][CH2:24][CH2:23][O:22][CH2:21][CH2:20][O:19][CH2:18][CH2:17][O:16][CH2:15][CH2:14][O:13][CH2:12][CH2:11][O:10][CH3:9])=[CH:55][CH:54]=4)=[N:68][C:67]=3[N:60]([CH2:59][CH:53]3[CH2:54][CH2:55][CH2:56][CH2:57][CH2:58]3)[C:61]2=[O:62])[CH2:76][CH2:75][CH2:74][CH2:73][CH2:72]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 222449751,3-Bis(cyclohexylmethyl)-5,6-diaminouracilHCID 23501906Nonaethyleneglycol(4-carboxybenzyl)methyl ether3×

Product 1

HCID 101475631,3-Bis(cyclohexylmethyl)-8-[4-(2,5,8,11,14,17,20,23,26,29-decaoxatriacont-1-yl)phenyl]-3,7-dihydro-1h-purine-2,6-dione

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent3×

Procedure

To a solution of nonaethyleneglycol(4-carboxybenzyl)methyl ether (0.45 g, 0.80 mmol) from Example 97 part (a) above, in dichloromethane (15 ml) was added oxalyl chloride (Fluka, 0.14 ml, 1.6 mmol) and N,N dimethylformamide (one drop). This solution was allowed to stir for 0.5 hours and the volatiles were removed in vacuo to give a tan oil. This material was dissolved in dichloromethane (20 ml) and a solution of triethylamine (0.5 ml, 3.8 mmol) and 1,3-bis(cyclohexylmethyl)-5,6-diaminouracil from Example 21, part (a), (0.270 g, 0.80 mmol) in dichloromethane (10 ml) were added. This solution was allowed to stir at room temperature for 18 hours and the volatiles were removed in vacuo. The residue was dissolved in ethanol (25 ml) and the pH was adjusted to ˜13 by addition of 2N sodium hydroxide. The solution was allowed to stir at reflux for 0.5 hours and then cooled to room temperature. Chloroform (100 ml) was added and the solution was washed with 1N hydrochloric acid (50 ml), saturated aqueous sodium chloride (20 ml), dried over magnesium sulfate and filtered. The volatiles were removed in vacuo and the title compound was eluted from silica gel with 15% methanol-ethyl acetate as a tan waxy solid after solidification from ethyl acetate-hexanes (0.098 g, 14%). 1H-NMR (300 MHz, DMSO-d6) δ: 8.07 (d, J=8.2 Hz, 2H , phenylCH), 7.44 (d, J=8.1 Hz, 2H, phenylCH), 4.54 (s, 2H, CH2—phenyl), 3.89 (d, J=7.2 Hz, 2H, CH2N), 3.70 (d, J=7.2 Hz, 2H, CH2N ), 3.60-3.35 (m, 36H, 18CH2), 3.20 (s, 3H, CH3), 2.05-1.50 and 1.30-0.95 (m, 22H, cyclohexyl CH2's).

Workup

  1. customthe volatiles were removed in vacuo
  2. customto give a tan oil
  3. stirringto stir at room temperature for 18 hours
  4. customthe volatiles were removed in vacuo
  5. dissolutionThe residue was dissolved in ethanol (25 ml)
  6. additionthe pH was adjusted to ˜13 by addition of 2N sodium hydroxide
  7. stirringto stir
  8. temperatureat reflux for 0.5 hours
  9. additionChloroform (100 ml) was added
  10. washthe solution was washed with 1N hydrochloric acid (50 ml), saturated aqueous sodium chloride (20 ml)
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. customThe volatiles were removed in vacuo
  14. washthe title compound was eluted from silica gel with 15% methanol-ethyl acetate as a tan waxy solid after solidification from ethyl acetate-hexanes (0.098 g, 14%)

Sources & evidence

ORD record
ord-beb6fc88d96c470ea9f7dbefb7ce8cee
Source dataset
uspto-grants-2003_08
Patent number
US06608069B1

Reaction notes

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