Toluene → 6-[(2,2-Diphenylethyl)amino]-9-{(2R,3R,4S,5S)-5-[(ethylamino)carbonyl]-3,4-dihydroxytetrahydro-2-furanyl}-N-{2-[({[2-(1-piperidinyl)ethyl]amino}carbonyl)amino]ethyl}-9H-purine-2-carboxamide

HRID 10427Notes

Reaction equation

HRID 10427 reaction equation
[NH2:1][CH2:2][CH2:3][NH:4][C:5]([C:7]1[N:15]=[C:14]2[C:10]([N:11]=[CH:12][N:13]2[C@H:16]2[C@H:20]([OH:21])[C@H:19]([OH:22])[C@@H:18]([C:23]([NH:25][CH2:26][CH3:27])=[O:24])[O:17]2)=[C:9]([NH:28][CH2:29][CH:30]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[N:8]=1)=[O:6].[N:43]1([CH2:49][CH2:50][NH:51][C:52](N2C=CN=C2)=[O:53])[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]1.C1(C)C=CC=CC=1.C(O)(C)C>ClCCl>[C:31]1([CH:30]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:29][NH:28][C:9]2[N:8]=[C:7]([C:5]([NH:4][CH2:3][CH2:2][NH:1][C:52]([NH:51][CH2:50][CH2:49][N:43]3[CH2:48][CH2:47][CH2:46][CH2:45][CH2:44]3)=[O:53])=[O:6])[N:15]=[C:14]3[C:10]=2[N:11]=[CH:12][N:13]3[C@H:16]2[C@H:20]([OH:21])[C@H:19]([OH:22])[C@@H:18]([C:23]([NH:25][CH2:26][CH3:27])=[O:24])[O:17]2)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 1140TolueneHCID 3776IsopropanolHCID 11192424N-(2-aminoethyl)-6-[(2,2-diphenylethyl)amino]-9-{(2R,3R,4S,5S)-5-[(ethylamino)carbonyl]-3,4-dihydroxytetrahydro-2-furanyl}-9H-purine-2-carboxamideHCID 11253042N-[2-(1-Piperidinyl)ethyl]-1H-imidazole-1-carboxamide2×

Product 1

HCID 101469376-[(2,2-Diphenylethyl)amino]-9-{(2R,3R,4S,5S)-5-[(ethylamino)carbonyl]-3,4-dihydroxytetrahydro-2-furanyl}-N-{2-[({[2-(1-piperidinyl)ethyl]amino}carbonyl)amino]ethyl}-9H-purine-2-carboxamideYield 54.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-(2-Aminoethyl)-6-[(2,2-diphenylethyl)amino]-9-{(2R,3R,4S, 5S)-5-[(ethylamino)carbonyl]-3,4-dihydroxytetrahydro-2-furanyl}-9H-purine-2-carboxamide (Preparation 10) (90 mg, 0.15 mmol) and N-[2-(1-piperidinyl)ethyl]-1H-imidazole-1-carboxamide (Preparation 18) (36 mg, 0.16 mmol) were dissolved in dichloromethane (3 ml). Toluene (4 ml) and isopropanol (1 ml) were added and the dichloromethane removed by evaporation at atmospheric pressure. The residual solution was heated under reflux for four hours. TLC analysis showed the reaction to be incomplete so further N-[2-(1-piperidinyl)ethyl]-1H-imidazole-1-carboxamide (25 mg, 0.11 mmol) was added and heating continued for four hours. The solvent was removed under reduced pressure and the residue purified by column chromatography on silica gel eluting with dichloromethane:methanol concentrated aqueous ammonia (90:10:1, by volume). Product containing fractions were evaporated and the resulting solid triturated with diethyl ether, filtered and dried to afford the title compound as a white powder (60 mg).

Workup

  1. customthe dichloromethane removed by evaporation at atmospheric pressure
  2. temperatureThe residual solution was heated
  3. temperatureunder reflux for four hours
  4. customthe reaction
  5. additionwas added
  6. temperatureheating
  7. customThe solvent was removed under reduced pressure
  8. customthe residue purified by column chromatography on silica gel eluting with dichloromethane
  9. additionProduct containing fractions
  10. customwere evaporated
  11. customthe resulting solid triturated with diethyl ether
  12. filtrationfiltered
  13. customdried

Sources & evidence

ORD record
ord-c9095f644eb14828b9bed161b97caec1
Source dataset
uspto-grants-2006_08
Patent number
US07094769B2

Reaction notes

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