1,2-Dichloroethane → HCID 54684202, compound

HRID 1013015Notes

Reaction equation

HRID 1013015 reaction equation
C([O:8][C:9]1[C:14](=[O:15])[N:13]2[CH2:16][CH2:17][N:18]([CH2:22][C:23]([O-:25])=O)[C:19]([CH3:21])([CH3:20])[C:12]2=[N:11][C:10]=1[C:26]([NH:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1)=[O:27])C1C=CC=CC=1.[Li+].C(Cl)CCl.C1C=[CH:44][C:45]2N(O)N=[N:48][C:46]=2C=1>C(Cl)(Cl)Cl.C(N)C#C.[Hg](OC(C)=O)OC(C)=O>[F:36][C:33]1[CH:34]=[CH:35][C:30]([CH2:29][NH:28][C:26]([C:10]2[N:11]=[C:12]3[C:19]([CH3:21])([CH3:20])[N:18]([CH2:22][C:23]4[O:25][C:45]([CH3:44])=[CH:46][N:48]=4)[CH2:17][CH2:16][N:13]3[C:14](=[O:15])[C:9]=2[OH:8])=[O:27])=[CH:31][CH:32]=1

Participants

7

Reactant 3

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 67316527HCID 67316527, compound

Product 1

HCID 54684202HCID 54684202, compound

Reagents, catalysts & solvents 3

HCID 16683746DiacetyloxymercuryCatalystHCID 6212ChloroformSolventHCID 239041PropargylamineSolvent

Procedure

To a solution of lithium (3-(benzyloxy)-2-{[(4-fluorobenzyl)amino]carbonyl}-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydro-8H-pyrazino[1,2-a]pyrimidin-8-yl)acetate (1 eq.) in CHCl3, propargylamine (1.1), EDC (2 eq.) and HOBt (2 eq.) were added and the reaction mixture was stirred at room temperature for 3 hours. The solvent was removed under reduced pressure and the residue was taken up in EtOAc, washed with brine, dried (Na2SO4), and concentrated under reduced pressure. The resulting crude was directly dissolved in acetic acid and Hg(OAc)2 (0.1 eq.) was added. The mixture was heated at 100° C. overnight and was then concentrated under reduced pressure. The residue was directly purified by RP-HPLC and after lyophilisation of the desired fractions, the O-benzyl protected material was dissolved in MeOH and stirred 1 hour under an H2 atmosphere in the presence of 10% Pd/C. The catalyst was then filtered off through celite, the filtrate was concentrated under reduced pressure and then the residue was dissolved in MeCN and H2O and lyophilized to afford the titled oxazole. 1H-NMR (400 MHz, d6-DMSO) δ 12.17 (br. s, 1H), 9.43 (t, J=6.2 Hz, 1H), 7.37 (dd, J=8.1 Hz, J=5.7 Hz, 2H), 7.17 (t, J=8.9 Hz, 2H), 6.77 (s, 1H), 4.47 (d, J=6.2 Hz, 2H), 3.80 (s, 2H), 3.71 (t, J=5.0 Hz, 2H), 3.00 (t, J=5.1 Hz, 2H), 2.27 (s, 3H), 1.53 (s, 6H); MS (ES) C22H24FN5O4 requires 441. Found: 442 (M+H+).

Workup

  1. customThe solvent was removed under reduced pressure
  2. washwashed with brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe resulting crude was directly dissolved in acetic acid
  6. temperatureThe mixture was heated at 100° C. overnight
  7. concentrationwas then concentrated under reduced pressure
  8. customThe residue was directly purified by RP-HPLC
  9. dissolutionafter lyophilisation of the desired fractions, the O-benzyl protected material was dissolved in MeOH
  10. stirringstirred 1 hour under an H2 atmosphere in the presence of 10% Pd/C
  11. filtrationThe catalyst was then filtered off through celite
  12. concentrationthe filtrate was concentrated under reduced pressure
  13. dissolutionthe residue was dissolved in MeCN

Sources & evidence

ORD record
ord-68d79960d52d492f8f969ba917092b08
Source dataset
uspto-grants-2011_07
Patent number
US07981879B2

Reaction notes

Loading…