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

HRID 2098297노트

반응식

HRID 2098297 반응식
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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

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+).

후처리

  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

출처 및 근거

ORD 기록
ord-f5a341580f174983822d9869f0d0c23e
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08450479B2

반응 노트

불러오는 중…