Trifluoroacetic acid → HCID 54686288, compound

HRID 1013003Notes

Reaction equation

HRID 1013003 reaction equation
[CH2:1]([O:8][CH2:9][CH:10]([C:15]1[N:20]=[C:19]([C:21]([NH:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)=[O:22])[C:18]([OH:32])=[C:17]([OH:33])[N:16]=1)[NH:11][CH2:12][CH2:13]Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].FC(F)(F)C(O)=O>O1CCOCC1>[CH2:1]([O:8][CH2:9][CH:10]1[C:15]2=[N:20][C:19]([C:21]([NH:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)=[O:22])=[C:18]([OH:32])[C:17](=[O:33])[N:16]2[CH2:13][CH2:12][NH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 23665647Potassium tert-butoxideHCID 178523005HCID 178523005, compound

Product 1

HCID 54686288HCID 54686288, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
15 °C

Procedure

To a solution of 2-{2-(benzyloxy)-1-[(2-chloroethyl)amino]ethyl}-N-(4-fluorobenzyl)-5,6-dihydroxypyrimidine-4-carboxamide in dry 1,4-dioxane under nitrogen atmosphere potassium tert-butoxide (3 eq.) was added in one portion. The resulting suspension was aged at 120° C. for 2 hours. The reaction mixture was cooled to about 15° C. then acidified with trifluoroacetic acid to pH=3-4. The solvent was removed under reduced pressure and the residue, dissolved in the minimum amount of MeOH, was applied on cation-exchange resin cartridges (Varian MEGA BOND ELUTE SCX), the cartridges washed with MeOH and the crude product was eluted with 1M ammonia in methanol. The pooled eluants were concentrated to dryness under reduced pressure to get 9-[(benzyloxy)methyl]-N-(4-fluorobenzyl)-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-4H-pyrazino[1,2-a]pyrimidine-2-carboxamide as a brown oil (85% yield). The crude product was purified by RP HPLC (C18, 5 μM, H2O/MeCN with 1% of TFA as eluant) and product was obtained after freeze drying of appropriate fractions.

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue, dissolved in the minimum amount of MeOH
  3. washwas applied on cation-exchange resin cartridges (Varian MEGA BOND ELUTE SCX)
  4. washthe cartridges washed with MeOH
  5. washthe crude product was eluted with 1M ammonia in methanol
  6. concentrationThe pooled eluants were concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-d127fc9824384c1fb66ad2f12a5b25c5
Source dataset
uspto-grants-2011_07
Patent number
US07981879B2

Reaction notes

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