Hydrochloric Acid → 4-Oxo-3-(2-oxobutyl)-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide

HRID 2098298Notes

Reaction equation

HRID 2098298 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].BrC[C:39](=[O:42])[CH2:40][CH3:41].Cl>C(#N)C>[O:26]=[C:25]1[N:24]([CH2:23][C:39](=[O:42])[CH2:40][CH3:41])[N:33]=[N:32][C:31]2=[C:30]([C:34]([NH2:36])=[O:35])[N:29]=[CH:28][N:27]12

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 5394TemozolomideHCID 131561-Bromo-2-butanoneHCID 1296629601,8-Diazabicycloundec-7ene

Product 1

HCID 441288084-Oxo-3-(2-oxobutyl)-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamideYield 33.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

1,8-Diazabicycloundec-7-ene (DBU) (150 μL, 1.00 mmol, 1.4 eq.) was added dropwise to a suspension of the hydroxymethyl derivative of temozolomide (150 mg, 0.71 mmol) and 1-bromo-2-butanone (90%, stabilized with CaCO3) (330 μL, 2.91 mmol, 4.1 eq.) in acetonitrile (4 mL). 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 1-bromo-2-butanone. The precipitate was filtered and washed with diethyl ether and 59 mg of a pale yellow/green solid were obtained (33% crude). LCMS: crude product (99.5% pure); m/z: 523.4 (2M+Na)+, 273.2 (M+Na)+, 251.3 ((MH+)+, 100). 1H NMR (d6 DMSO): 8.90 (s, 1H), 7.90 (s, 1H), 7.75 (s, 1H), 5.37 (s, 2H), 2.67-2.72 (q, 2H, J=7.2 Hz), 0.99-1.03 (t, 3H, J=7.2 Hz).

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 1-bromo-2-butanone
  7. filtrationThe precipitate was filtered
  8. washwashed with diethyl ether

Sources & evidence

ORD record
ord-1e912e2af8cf4f3fac5280a2f0a1e8ce
Source dataset
uspto-grants-2013_05
Patent number
US08450479B2

Reaction notes

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