Dimethylformamide → 3-cyclopropyl-3-(4-(7-(5-methyl-1,3,4-thiadiazol-2-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile

HRID 1853000노트

반응식

HRID 1853000 반응식
[NH:1]1[CH:5]=[C:4]([C:6]2[N:11]3[CH:12]=[CH:13][N:14]=[C:10]3[CH:9]=[C:8]([C:15]3[S:16][C:17]([CH3:20])=[N:18][N:19]=3)[N:7]=2)[CH:3]=[N:2]1.[CH:21]1([CH:24]=[CH:25][C:26]#[N:27])[CH2:23][CH2:22]1.CN(C=O)C.C1CCN2C(=NCCC2)CC1>CCOC(C)=O>[CH:21]1([CH:24]([N:2]2[CH:3]=[C:4]([C:6]3[N:11]4[CH:12]=[CH:13][N:14]=[C:10]4[CH:9]=[C:8]([C:15]4[S:16][C:17]([CH3:20])=[N:18][N:19]=4)[N:7]=3)[CH:5]=[N:1]2)[CH2:25][C:26]#[N:27])[CH2:23][CH2:22]1

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2회HCID 670567823-Cyclopropylacrylonitrile2회HCID 674570012-(5-(1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-7-yl)-5-methyl-1,3,4-thiadiazole

생성물 1

HCID 674576133-cyclopropyl-3-(4-(7-(5-methyl-1,3,4-thiadiazol-2-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile수율 31.2%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

In a 20 mL flask, 2-(5-(1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-7-yl)-5-methyl-1,3,4-thiadiazole (17.4 mg, 0.0614 mmol) and 3-cyclopropylacrylonitrile (Preparation B; 17.2 mg, 0.184 mmol) were dissolved in DMF (614 μL, 0.0614 mmol). To this was added DBU (23.0 μA, 0.154 mmol) and stirred at ambient temperature for 40 h. The reaction was incomplete, so another portion of DBU (23.0 μA, 0.154 mmol) and 3-cyclopropylacrylonitrile (17.2 mg, 0.184 mmol) were added. After 4 hours, the reaction mixture was diluted in EtOAc, and washed with water and brine. The organic layer was dried with MgSO4, filtered and concentrated down to a yellow oil. The crude material was purified by silica chromatography using a 0-10% MeOH/EtOAc gradient to afford 3-cyclopropyl-3-(4-(7-(5-methyl-1,3,4-thiadiazol-2-yl)imidazo[1,2-c]pyrimidin-5-yl)-1H-pyrazol-1-yl)propanenitrile (7.2 mg, 31% yield). MS (apci) m/z=377.2 (M+H).

후처리

  1. waitAfter 4 hours
  2. washwashed with water and brine
  3. dry with materialThe organic layer was dried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated down to a yellow oil
  6. customThe crude material was purified by silica chromatography

출처 및 근거

ORD 기록
ord-030e8ef163a643f7a4661a38a06202f5
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08962596B2

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