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 1853000Notes

Reaction equation

HRID 1853000 reaction equation
[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

Participants

6

Reactant 4

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

Product 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)propanenitrileYield 31.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-030e8ef163a643f7a4661a38a06202f5
Source dataset
uspto-grants-2015_02
Patent number
US08962596B2

Reaction notes

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