Hydrochloric Acid → Ethyl 2-(8-carbamoyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)acetate

HRID 2098297Notes

Reaction equation

HRID 2098297 reaction equation
N1(C2CCCCCCCCCC2)CCCN=CCCCCC1.[CH3:23][N:24]1[N:33]=[N:32][C:31]2[N:27]([CH:28]=[N:29][C:30]=2[C:34]([NH2:36])=[O:35])[C:25]1=[O:26].IC[C:39]([O:41][CH2:42][CH3:43])=[O:40].Cl>C(#N)C>[C:34]([C:30]1[N:29]=[CH:28][N:27]2[C:25](=[O:26])[N:24]([CH2:23][C:39]([O:41][CH2:42][CH3:43])=[O:40])[N:33]=[N:32][C:31]=12)(=[O:35])[NH2:36]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 5394TemozolomideHCID 12183Ethyl iodoacetateHCID 1296629601,8-Diazabicycloundec-7ene

Product 1

HCID 10978381Ethyl 2-(8-carbamoyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazin-3(4H)-yl)acetateYield 13.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1,8-Diazabicycloundec-7-ene (DBU) (32 μL, 0.215 mmol, 1.5 eq.) was added dropwise to a suspension of the hydroxymethyl derivative of Temozolomide (3-(hydroxymethyl)-4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide) (30 mg, 0.143 mmol) and ethyl iodoacetate (43 μL, 0.357 mmol, 2.5 eq.) in acetonitrile (700 μL). The resulting green suspension became homogeneous and was stirred overnight. The reaction was acidified with 1 N HCl and the yellow solution was extracted four times with ethyl acetate. The combined organic extracts were washed with water and then dried over MgSO4. The solvent was removed under vacuum and the pale yellow solid was triturated with diethyl ether to remove the excess of ethyl iodoacetate. The precipitate was filtered to give 5 mg of the title compound as a yellow solid (13% crude). 1H NMR (DMSO d6): 8.93 (s, 1H), 7.89 (s, 1H), 7.75 (s, 1H), 5.23 (s, 2H), 4.20-4.23 (q, 2H, J=7.1 Hz), 1.22-1.26 (t, 3H, J=7.1 Hz). LCMS: 97% pure; m/z: 289.4 (M+Na+), 267.5 (MH+).

Workup

  1. extractionthe yellow solution was extracted four times with ethyl acetate
  2. washThe combined organic extracts were washed with water
  3. dry with materialdried over MgSO4
  4. customThe solvent was removed under vacuum
  5. customthe pale yellow solid was triturated with diethyl ether
  6. customto remove the excess of ethyl iodoacetate
  7. filtrationThe precipitate was filtered

Sources & evidence

ORD record
ord-f5a341580f174983822d9869f0d0c23e
Source dataset
uspto-grants-2013_05
Patent number
US08450479B2

Reaction notes

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