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 353611노트

반응식

HRID 353611 반응식
[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

참가 물질

6

반응물 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-carboxamide2회

생성물 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-carboxamide수율 54.9%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

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)

후처리

  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

출처 및 근거

ORD 기록
ord-6bfbd6ff0e82456e924a9ef06f99d6d0
출처 데이터셋
uspto-grants-2004_06
특허 번호
US06753322B2

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