Uracil → HCID 67437509, compound

HRID 467805Notes

Reaction equation

HRID 467805 reaction equation
[NH:1]1[CH:8]=[CH:7][C:5](=O)NC1=O.CC[N:11](C(C)C)[CH:12]([CH3:14])[CH3:13].[C:18](=[O:21])([O-])[O-].[K+].[K+].N1C=[CH:28][CH:27]=NC=1>C1COCC1.C(N(CC)CC)C>[CH:12]([NH:11][C:18]([C@@H:7]1[CH2:5][CH2:28][CH2:27][C@@H:8]1[NH2:1])=[O:21])([CH3:14])[CH3:13]

Participants

7

Reactant 4

HCID 1174UracilHCID 9260Pyrimidine2×HCID 11430Potassium CarbonateHCID 81531Diisopropylethylamine

Product 1

HCID 67437509HCID 67437509, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

A correspondingly R2-substituted 2,4-dichloropyrimidine A-1 (commercially obtainable or prepared by chlorination of the corresponding uracil as described for A-1a by way of example) is dissolved in THF (dioxane, DMA, NMP, acetone or DCM) (approx. 2-5 mL/mmol), 1-1.6 eq Hünig base (triethylamine, potassium carbonate or another suitable base) and the reaction mixture is maintained at a controlled temperature (−78° C. for very reactive pyrimidines, RT or elevated temperature for pyrimidines with a tendency to be less reactive). Then approx. 0.75-1 eq of the amine, dissolved in the corresponding solvent (see above), are added and the reaction mixture is stirred or thawed or heated for a specific time at the corresponding temperature, depending on the reactivity of the pyrimidine used. After the reaction has ended (reaction monitored by HPLC or DC) the reaction mixture is combined with silica gel and all the volatile constituents are eliminated in vacuo. Purification by column chromatography yields the desired substitution products. Depending on the group R2 of the pyrimidine the two possible regioisomers are produced in different ratios. They can generally be separated by chromatography.

Workup

  1. additionare added
  2. temperatureheated for a specific time at the corresponding temperature
  3. custom(reaction monitored by HPLC or DC) the reaction mixture
  4. customPurification by column chromatography
  5. customyields the desired substitution products
  6. customare produced in different ratios
  7. customThey can generally be separated by chromatography

Sources & evidence

ORD record
ord-a9fcaa4dfeb240458a7ad773aa2cda3a
Source dataset
uspto-grants-2014_01
Patent number
US08623887B2

Reaction notes

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