Triethylamine → 5'-O-[N-[N-{N-(Nalpha,Nepsilon-dibenzyloxycarbonyllysyl)alanyl}phenylalanyl]isoleucyl]-5-fluorouridine

HRID 329840Notes

Reaction equation

HRID 329840 reaction equation
Cl.[NH2:2][C@H:3]([C:5]([NH:7][C@H:8]([C:16]([NH:18][C@H:19]([C:24]([O:26][CH2:27][C@H:28]1[O:32][C@@H:31]([N:33]2[CH:40]=[C:39]([F:41])[C:37](=[O:38])[NH:36][C:34]2=[O:35])[C@H:30]([OH:42])[C@@H:29]1[OH:43])=[O:25])[C@H:20]([CH2:22][CH3:23])[CH3:21])=[O:17])[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:6])[CH3:4].[CH2:44]([O:51][C:52]([NH:54][C@H:55]([C:71](O)=[O:72])[CH2:56][CH2:57][CH2:58][CH2:59][NH:60][C:61]([O:63][CH2:64][C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1)=[O:62])=[O:53])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.C(P(C#N)(CC)=O)C.C(N(CC)CC)C>CN(C)C=O>[CH2:44]([O:51][C:52]([NH:54][C@H:55]([C:71]([NH:2][C@H:3]([C:5]([NH:7][C@H:8]([C:16]([NH:18][C@H:19]([C:24]([O:26][CH2:27][C@H:28]1[O:32][C@@H:31]([N:33]2[CH:40]=[C:39]([F:41])[C:37](=[O:38])[NH:36][C:34]2=[O:35])[C@H:30]([OH:42])[C@@H:29]1[OH:43])=[O:25])[C@H:20]([CH2:22][CH3:23])[CH3:21])=[O:17])[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:6])[CH3:4])=[O:72])[CH2:56][CH2:57][CH2:58][CH2:59][NH:60][C:61]([O:63][CH2:64][C:65]1[CH:66]=[CH:67][CH:68]=[CH:69][CH:70]=1)=[O:62])=[O:53])[C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 7269422N2,N6-Bis[(phenylmethoxy)carbonyl]-L-lysineHCID 13586794DiethylphosphorylcyanideHCID 186373365'-O-{N-(N-alanylphenylalanyl)isoleucyl}-5-fluorouridine hydrochloride

Product 1

HCID 867436835'-O-[N-[N-{N-(Nalpha,Nepsilon-dibenzyloxycarbonyllysyl)alanyl}phenylalanyl]isoleucyl]-5-fluorouridineYield 52.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.04 Grams (1.65 mmol) of 5'-O-{N-(N-alanylphenylalanyl)isoleucyl}-5-fluorouridine hydrochloride obtained in Example 9 was dissolved in dimethylformamide (10 ml), and 0.815 g (1.97 mmol) of Nα,Nε -di-benzyloxycarbonyllysine and 0.375 g (2.30 mmol) of diethylphosphoryl cyanide were then added. To this solution was added under ice-cooling 0.60 g (5.90 mmol) of triethylamine, and the mixture was stirred for 1 hour at room temperature. The reaction liquid was concentrated under reduced pressure, and the residue was subjected to separation/purification by way of silica gel column chromatography (first time: a linear gradient of chloroform containing 2%→6% methanol; second time: a linear gradient of chloroform containing 3%→6% methanol) whereby 0.85 g (52.3%) of 5'-O-[N-[N-{N-(Nα,Nε -dibenzyloxycarbonyllysyl)alanyl}phenylalanyl]isoleucyl]-5-fluorouridine was obtained as a colorless powdery solid.

Workup

  1. additionTo this solution was added under ice-
  2. customThe reaction liquid
  3. concentrationwas concentrated under reduced pressure
  4. customthe residue was subjected to separation/purification by way of silica gel column chromatography (first time

Sources & evidence

ORD record
ord-757ca8aac73843af89c56dc958ca1577
Source dataset
uspto-grants-1990_01
Patent number
US04892939

Reaction notes

Loading…