Formamide → Uridine 5'-triphosphate

HRID 1167392Notes

Reaction equation

HRID 1167392 reaction equation
C(N)=O.C(N(CC)CC)C.[O-:11][P:12]([O:15][P:16]([O-])([O-:18])=[O:17])(=[O:14])[O-:13].C(N(CCCC)CCCC)CCC.[P:33]([O:37][CH2:38][C@H:39]1[O:43][C@@H:42]([N:44]2[CH:51]=[CH:50][C:48](=[O:49])[NH:47][C:45]2=[O:46])[C@H:41]([OH:52])[C@@H:40]1[OH:53])([OH:36])([OH:35])=[O:34]>O1CCOCC1.CC(N(C)C)=O.N1C=CC=CC=1>[CH:50]1[C:48](=[O:49])[NH:47][C:45](=[O:46])[N:44]([C@@H:42]2[O:43][C@H:39]([CH2:38][O:37][P:33]([O:35][P:16]([O:15][P:12]([OH:14])([OH:13])=[O:11])([OH:18])=[O:17])([OH:36])=[O:34])[C@@H:40]([OH:53])[C@H:41]2[OH:52])[CH:51]=1

Participants

9

Reactant 5

HCID 713FormamideHCID 6030Uridine MonophosphateHCID 7622Tributylamine3×HCID 8471TriethylamineHCID 644102Pyrophosphate

Product 1

HCID 6133Uridine 5'-triphosphate

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 312751,4-DioxaneSolventHCID 31374DimethylacetamideSolvent

Procedure

Formamide (2.5 ml) and pyridine (7.6 ml) were added to a dehydrated triethylamine salt (10 mmol) of pyrophosphate (TEA-PPi), followed by stirring the resultant mixture. To a dehydrated tributylamine salt of uridine 5′-monophosphate (UMP-TBA) (10 mmol) placed in another vessel, DMAC (3.6 ml), dioxane (3.2 ml), and tributylamine (3.3 ml) were added and stirred, and DPC (2.3 ml) was added dropwise thereto. The mixture was stirred at room temperature for one hour, to thereby form UMP-DPP, which was added to the aforementioned dehydrated solution of TEA-PPi prepared in advance. The reaction mixture was stirred at room temperature for one hour, forming UTP. DMAC (7.2 ml) was added to a tributylamine salt of 2′-deoxycytidine 5′-monophosphate (TBA-dCMP) (4.9 g, 10 mmol) placed in another vessel, to thereby form a suspension, and DPC (2.2 ml, 1.1 equivalents) was added to the suspension. The resultant mixture was stirred for 40 minutes, and tributylamine (TBA) (9.5 ml) was added to the mixture. Another 20 minutes stirring was carrier out, to thereby prepare dCMP-DPP. The thus-prepared dCMP-DPP solution was added to the aforementioned synthesized UTP solution prepared in advance, and the mixture was stirred at room temperature for 56 hours. Reaction was terminated by adding water, and the pH of the reaction mixture was adjusted to 11 by adding a 30% aqueous sodium hydroxide solution. After the solvent was removed by concentration, the pH was adjusted to 7.0 by adding a 6 mol/L hydrochloric acid. The mixture was partitioned with ethyl acetate. The aqueous layer formed by partitioning was subjected to HPLC analysis (272 nm), revealing that the synthesis yield of dCP4U was 37.7%.

Workup

  1. additionDPC (2.3 ml) was added dropwise
  2. stirringThe mixture was stirred at room temperature for one hour
  3. customto thereby form UMP-DPP, which
  4. additionwas added to the aforementioned dehydrated solution of TEA-PPi
  5. customprepared in advance
  6. stirringThe reaction mixture was stirred at room temperature for one hour

Sources & evidence

ORD record
ord-4fda579746a74372855647d514e88c1b
Source dataset
uspto-grants-2003_09
Patent number
US06617444B1

Reaction notes

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