Diethyl Ether → HCID 54684172, compound

HRID 1012980Notes

Reaction equation

HRID 1012980 reaction equation
Cl[CH2:2][CH2:3][NH:4][C:5]([C:8]1[N:13]=[C:12]([C:14]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)=[O:15])[C:11]([OH:25])=[C:10]([OH:26])[N:9]=1)([CH3:7])[CH3:6].C([O-])([O-])=O.[Cs+].[Cs+].CCOCC>O1CCOCC1>[F:24][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][NH:16][C:14]([C:12]2[N:13]=[C:8]3[C:5]([CH3:7])([CH3:6])[NH:4][CH2:3][CH2:2][N:9]3[C:10](=[O:26])[C:11]=2[OH:25])=[O:15])=[CH:19][CH:20]=1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 10796Cesium carbonateHCID 178457306HCID 178457306, compound

Product 1

HCID 54684172HCID 54684172, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

2-{1-[(2-Chloroethyl)amino]-1-methylethyl}-N-(4-fluorobenzyl)-5,6-dihydroxypyrimidine-4-carboxamide (1 eq.) was dissolved in 1,4-dioxane and Cs2CO3 (1 eq.) was added. The reaction mixture was stirred at 100° C. overnight, then cooled to room temperature and the solvent was removed under reduced pressure. The resulting brown oil was suspended in MeOH, filtered and the filtrate was evaporated to give a residue that was purified on Cation Exchange Resin (Varian Mega Bond Elute SCX). After washing with MeOH, the product was collected eluting with 2N NH3 solution in MeOH. The fractions containing the desired material were concentrated under reduced pressure to yield, after trituration with Et2O the title compound as a yellow solid. A small portion of this crude was purified by RP HPLC (C18, 5 μM, H2O/MeCN with 1% of TFA as eluant) affording the pure product as TFA salt. 1H NMR (400 MHz, d6-DMSO) δ 9.41 (bs, 1H), 7.37 (dd, J=8.6 Hz, J=5.7 Hz, 2H), 7.17 (t, J=8.6 Hz, 2H), 4.48 (d, J=6.4 Hz, 2H), 3.74 (t, J=5.5 Hz, 2H), 3.06 (t, J=5.5 Hz, 2H), 1.46 (s, 6H); MS (ES) C17H19FN4O3 requires: 346. Found: 347 (M+H+).

Workup

  1. temperaturecooled to room temperature
  2. customthe solvent was removed under reduced pressure
  3. filtrationfiltered
  4. customthe filtrate was evaporated
  5. customto give a residue that
  6. customwas purified on Cation Exchange Resin (Varian Mega Bond Elute SCX)
  7. washAfter washing with MeOH
  8. customthe product was collected
  9. washeluting with 2N NH3 solution in MeOH
  10. additionThe fractions containing the desired material
  11. concentrationwere concentrated under reduced pressure
  12. customto yield

Sources & evidence

ORD record
ord-dad33e67b64f4d648730de237494b8fb
Source dataset
uspto-grants-2011_07
Patent number
US07981879B2

Reaction notes

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