Triethylamine → 5'-O-(N-Lysylisoleucyl)-5-fluorouridine dihydrochloride

HRID 329836Notes

Reaction equation

HRID 329836 reaction equation
[ClH:1].[NH2:2][C@H:3]([C:8]([O:10][CH2:11][C@H:12]1[O:16][C@@H:15]([N:17]2[CH:24]=[C:23]([F:25])[C:21](=[O:22])[NH:20][C:18]2=[O:19])[C@H:14]([OH:26])[C@@H:13]1[OH:27])=[O:9])[C@H:4]([CH2:6][CH3:7])[CH3:5].C(OC([NH:38][C@H:39]([C:55](O)=[O:56])[CH2:40][CH2:41][CH2:42][CH2:43][NH:44]C(OCC1C=CC=CC=1)=O)=O)C1C=CC=CC=1.C(P(C#N)(CC)=O)C.C(N(CC)CC)C>CN(C)C=O>[ClH:1].[ClH:1].[NH2:38][C@H:39]([C:55]([NH:2][C@H:3]([C:8]([O:10][CH2:11][C@H:12]1[O:16][C@@H:15]([N:17]2[CH:24]=[C:23]([F:25])[C:21](=[O:22])[NH:20][C:18]2=[O:19])[C@H:14]([OH:26])[C@@H:13]1[OH:27])=[O:9])[C@H:4]([CH2:6][CH3:7])[CH3:5])=[O:56])[CH2:40][CH2:41][CH2:42][CH2:43][NH2:44]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 7269422N2,N6-Bis[(phenylmethoxy)carbonyl]-L-lysineHCID 13586794DiethylphosphorylcyanideHCID 186373305'-O-isoleucyl-5-fluorouridine hydrochloride

Product 1

HCID 186373355'-O-(N-Lysylisoleucyl)-5-fluorouridine dihydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.00 Gram (2.42 mmol) of 5'-O-isoleucyl-5-fluorouridine hydrochloride was dissolved in dimethylformamide (20 ml), and 1.00 g (2.85 mmol) of Nα,Nε -di-benzyloxycarbonyllysine and 0.67 g (3.69 mmol) of diethylphosphoryl cyanide were then added. To this solution was added under ice-cooling 1.54 g (15.2 mmol) of triethylamine, and the mixture was stirred overnight at room temperature. After addition of ice water the reaction liquid was extracted with chloroform (200 ml). The organic layer was dried (over Na2SO4) and concentrated under reduced pressure, and the residue was subjected to separation/purification by way of silica gel column chromatography (first time: 2.5×11 cm, chloroform containing 4% methanol; second time: 5×14 cm, a linear gradient of ethyl acetate-n-hexane (1:1) containing 0→6% methanol) whereby 0.46 g (26%) of 5'-O-{N-(Nα,Nε -di-benzyloxycarbonyllysyl)isoleucyl}-5-fluorouridine was obtained as a colorless powdery solid.

Workup

  1. additionTo this solution was added under ice-
  2. customthe reaction liquid
  3. extractionwas extracted with chloroform (200 ml)
  4. dry with materialThe organic layer was dried (over Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customthe residue was subjected to separation/purification by way of silica gel column chromatography (first time
  7. additionsecond time: 5×14 cm, a linear gradient of ethyl acetate-n-hexane (1:1) containing 0→6% methanol) whereby 0.46 g (26%) of 5'-O-{N-(Nα,Nε -di-benzyloxycarbonyllysyl)isoleucyl}-5-fluorouridine
  8. customwas obtained as a colorless powdery solid

Sources & evidence

ORD record
ord-8f9fb969e06c4209b90c3d26cea6b72a
Source dataset
uspto-grants-1990_01
Patent number
US04892939

Reaction notes

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