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 1853000ノート

反応式

HRID 1853000 の反応式
[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

参加物

6

反応物 4

HCID 6228DimethylformamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2 回HCID 670567823-Cyclopropylacrylonitrile2 回HCID 674570012-(5-(1H-pyrazol-4-yl)imidazo[1,2-c]pyrimidin-7-yl)-5-methyl-1,3,4-thiadiazole

生成物 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)propanenitrile収率 31.2%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-030e8ef163a643f7a4661a38a06202f5
出典データセット
uspto-grants-2015_02
特許番号
US08962596B2

反応ノート

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