1H-Isoindole-1,3(2H)-dione, 2-(2-bromoethyl)- → HCID 465659, compound

HRID 1769219Notes

Reaction equation

HRID 1769219 reaction equation
Br[CH2:2][CH2:3][N:4]1[C:8](=[O:9])[C:7]2=[CH:10][CH:11]=[CH:12][CH:13]=[C:6]2[C:5]1=[O:14].[CH3:15][C:16]1[C:22](=[O:23])[NH:21][C:19](=[O:20])[N:18]([C@@H:24]2[O:28][C@H:27]([CH2:29][OH:30])[C@@H:26]([N:31]=[N+:32]=[N-:33])[CH2:25]2)[CH:17]=1.C[O-].[Na+].C(Cl)(Cl)Cl.CO.CC(O)=O>CN1C(=O)N(C)CCC1>[C:8]1(=[O:9])[N:4]([CH2:3][CH2:2][N:21]2[C:22](=[O:23])[C:16]([CH3:15])=[CH:17][N:18]([C@@H:24]3[O:28][C@H:27]([CH2:29][OH:30])[C@@H:26]([N:31]=[N+:32]=[N-:33])[CH2:25]3)[C:19]2=[O:20])[C:5](=[O:14])[C:6]2=[CH:13][CH:12]=[CH:11][CH:10]=[C:7]12

Participants

6

Reactant 4

HCID 113251H-Isoindole-1,3(2H)-dione, 2-(2-bromoethyl)-3×HCID 35370ZidovudineHCID 10942334Sodium Methoxide3×HCID 21866353chloroform methanol HOAc

Product 1

HCID 465659HCID 465659, compound

Reagents, catalysts & solvents 1

HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Conditions

Temperature
70 °C

Procedure

A solution of 300 mg N-(2-bromoethyl)-phthalimide (BEP) and 274 mg AZT in 1 ml of sieve-dried DMPU was treated with 300 ul of sodium methoxide solution (4.4M NaOMe in MeOH) and heated at 70° C. for one hour. Another 300 ul of NaOMe solution and 175 mg BEP were added and the solution again heated at 70° C. for a total of 3.5 hours. The reaction was followed by analytical TLC on silica gel-F 250 um using a solvent system of CHCl3 /MeOH/HOAc (95+5+0.5) and was found to be incomplete. Addition of more NaOMe solution and BEP did not increase the yield of the desired product. Unreacted BEP (Rf =0.81) and AZT (Rf =0.2) were identified using reference markers and by their UV spectra. The product (Rf =0.4) and a byproduct (Rf =0.62) were differentiated on the basis of their UV spectra and immunological activity. The reaction mixture was acidified with HOAc, diluted with 15 ml deionized water and extracted with EtOAc. The organic phase was washed with saturated NaCl solution, dried over Na2SO4, concentrated under reduced pressure and chromatographed by preparative TLC on silica gel-F 2000 um using the solvent system CHCl3 /MeOH/HOAc (96.5+3.3+0.3) and the product eluted with MeOH.

Workup

  1. temperaturethe solution again heated at 70° C. for a total of 3.5 hours

Sources & evidence

ORD record
ord-5595ad08d4c6478d9234998c6e778400
Source dataset
uspto-grants-1995_01
Patent number
US05380825

Reaction notes

Loading…