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

HRID 329837Notes

Reaction equation

HRID 329837 reaction equation
Cl.[NH2:2][C@H:3]([C:5]([NH:7][C@H:8]([C:13]([O:15][CH2:16][C@H:17]1[O:21][C@@H:20]([N:22]2[CH:29]=[C:28]([F:30])[C:26](=[O:27])[NH:25][C:23]2=[O:24])[C@H:19]([OH:31])[C@@H:18]1[OH:32])=[O:14])[C@H:9]([CH2:11][CH3:12])[CH3:10])=[O:6])[CH3:4].[CH2:33]([O:40][C:41]([NH:43][C@H:44]([C:60](O)=[O:61])[CH2:45][CH2:46][CH2:47][CH2:48][NH:49][C:50]([O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:51])=[O:42])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(P(C#N)(CC)=O)C.C(N(CC)CC)C>CN(C)C=O>[CH2:33]([O:40][C:41]([NH:43][C@H:44]([C:60]([NH:2][C@H:3]([C:5]([NH:7][C@H:8]([C:13]([O:15][CH2:16][C@H:17]1[O:21][C@@H:20]([N:22]2[CH:29]=[C:28]([F:30])[C:26](=[O:27])[NH:25][C:23]2=[O:24])[C@H:19]([OH:31])[C@@H:18]1[OH:32])=[O:14])[C@H:9]([CH2:11][CH3:12])[CH3:10])=[O:6])[CH3:4])=[O:61])[CH2:45][CH2:46][CH2:47][CH2:48][NH:49][C:50]([O:52][CH2:53][C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=1)=[O:51])=[O:42])[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 7269422N2,N6-Bis[(phenylmethoxy)carbonyl]-L-lysineHCID 13586794DiethylphosphorylcyanideHCID 186373335'-O-(N-alanylisoleucyl)-5-fluorouridine hydrochloride

Product 1

HCID 678967925'-O-[N-{N-(Nalpha,Nepsilon-di benzyloxycarbonyllysyl)alanyl}isoleucyl]-5-fluorouridineYield 45.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

0.46 Gram of 5'-O-(N-alanylisoleucyl)-5-fluorouridine hydrochloride obtained in Example 4 was dissolved in dimethylformamide (30 ml), and 1.42 g (3.42 mmol) of Nα,Nε -di-benzyloxycarbonyllysine and 0.90 g (5.52 mmol) of diethylphosphoryl cyanide were then added. To this solution was added under ice-cooling a solution of 1.30 g (12.9 mmol) of triethylamine in dimethylformamide, and the mixture was stirred for 1 hour at room temperature, allowed to stand overnight at room temperature and concentrated under reduced pressure. The residue was subjected to separation/purification by way of silica gel column chromatography (5×20 cm; a linear gradient of chloroform containing 3%→6% methanol) whereby 1.20 g (45.9%) of 5'-O-[N-{N-(Nα,Nε -di benzyloxycarbonyllysyl)alanyl}isoleucyl]-5-fluorouridine was obtained as a colorless powdery solid.

Workup

  1. additionTo this solution was added under ice-
  2. waitto stand overnight at room temperature
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was subjected to separation/purification by way of silica gel column chromatography (5×20 cm

Sources & evidence

ORD record
ord-5158e0e1a36c4dad890805fbfe92bf1b
Source dataset
uspto-grants-1990_01
Patent number
US04892939

Reaction notes

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