Triethylamine → 5'-O-[N-{(N-benzyloxycarbonylphenylalanyl)alanyl}isoleucyl]-5-fluorouridine

HRID 329839Notes

Reaction equation

HRID 329839 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:52](O)=[O:53])[CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)=[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.C(N(CC)C=O)C>CN(C)C=O>[CH2:33]([O:40][C:41]([NH:43][C@H:44]([C:52]([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:53])[CH2:45][C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1)=[O:42])[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 12051DiethylformamideHCID 70878Benzyloxycarbonyl-L-phenylalanineHCID 13586794DiethylphosphorylcyanideHCID 186373335'-O-(N-alanylisoleucyl)-5-fluorouridine hydrochloride

Product 1

HCID 186373385'-O-[N-{(N-benzyloxycarbonylphenylalanyl)alanyl}isoleucyl]-5-fluorouridineYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

0.46 Gram of 5'-O-(N-alanylisoleucyl)-5-fluorouridine hydrochloride obtained in Example 4 was dissolved in dimethylformamide (20 ml), and 1.51 g (5.30 mmol) of N-benzyloxycarbonylphenylalanine and 1.10 g (6.74 mmol) of diethylphosphoryl cyanide were then added. To this solution was added dropwise under ice-cooling a solution of 2.40 g (23.8 mmol) of triethylamine in diethylformamide (3 mmol), and the reaction liquid was kept for 17 hours at -20° C. and then concentrated under reduced pressure. The residue was dissolved in chloroform (200 ml) and the solution was washed with a 3% aqueous solution of potassium hydrogen carbonate (100 ml). The aqueous layer was further extracted with chloroform (100 ml). These organic layers were dried (over Na2SO4) and then 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 3%→6% methanol; second time: a linear gradient of chloroform containing 3%→6% methanol) whereby 1.25 g (35%) of 5'-O-[N-{(N-benzyloxycarbonylphenylalanyl)alanyl}isoleucyl]-5-fluorouridine was obtained as a colorless powdery solid.

Workup

  1. additionTo this solution was added dropwise under ice-
  2. customthe reaction liquid
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in chloroform (200 ml)
  5. washthe solution was washed with a 3% aqueous solution of potassium hydrogen carbonate (100 ml)
  6. extractionThe aqueous layer was further extracted with chloroform (100 ml)
  7. dry with materialThese organic layers were dried (over Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. customthe residue was subjected to separation/purification by way of silica gel column chromatography (first time

Sources & evidence

ORD record
ord-c5fb5cc41b964e919511dd37f314dd52
Source dataset
uspto-grants-1990_01
Patent number
US04892939

Reaction notes

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