Azobisisobutyronitrile → HCID 135583860, compound

HRID 489427Notes

Reaction equation

HRID 489427 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:16]=[C:15]2[C:10]([NH:11][C:12]([CH3:26])=[C:13]([C:24]#[N:25])[CH:14]2[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[Cl:23])=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:27]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N>C1C=CC=CC=1>[Br:27][CH2:26][C:12]1[NH:11][C:10]2=[N:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH:16]=[C:15]2[CH:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[Cl:23])[C:13]=1[C:24]#[N:25]

Participants

5

Reactant 3

HCID 6547AzobisisobutyronitrileHCID 67184N-bromobutanimideHCID 135584021HCID 135584021, compound

Product 1

HCID 135583860HCID 135583860, compound

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A solution of 4-(2-chlorophenyl)-5-cyano-4,7-dihydro-6-methyl-2H-pyrazolo[3,4-b]pyridine (22.9 g), di-t-butyl dicarbonate (19.4 g) and dimethylaminopyridine (0.5 g) in tetrahydrofuran (200 ml) was stirred at room temperature for 30 minutes. The reaction mixture was ice-cooled and the precipitated crystals were collected by filtration to give 2-(t-butoxycarbonyl)-4-(2-chlorophenyl)-5-cyano-4,7-dihydro-6-methyl-2H-pyrazolo[3,4-b]pyridine (21.8 g) as white crystals. 2-(t-Butoxycarbonyl)-4-(2-chlorophenyl)-5-cyano-4,7-dihydro-6-methyl-2H-pyrazolo[3,4-b]pyridine (5.0 g), N-bromosuccinimide (2.5 g) and azobisisobutyronitrile (66 mg) were suspended in benzene (50 ml) and the suspension was stirred for 1 hour. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate (2:1)) and crystallized from ethyl acetate to give 6-bromomethyl-2-(t-butoxycarbonyl)-4-(2-chlorophenyl)-5-cyano-4,7-dihydro-2H-pyrazolo[3,4-b]pyridine as white crystals. To a suspension of sodium hydride (32 mg) in DMF (10 ml) was added morpholine (70 μl) and the mixture was stirred at room temperature for 30 minutes. To the reaction mixture was added 6-bromomethyl-2-(t-butoxycarbonyl)-4-(2-chlorophenyl)-5-cyano-4,7-dihydro-2H-pyrazolo[3,4-b]pyridine (0.36 g) and the mixture was stirred under ice-cooling for 1 hour. To the reaction mixture was added water, and the precipitated crystals were collected by filtration and washed with hexane to give 2-(t-butoxycarbonyl)-4-(2-chlorophenyl)-5-cyano-4,7-dihydro-6-(morpholin-4-yl)methyl-2H-pyrazolo[3,4-b]pyridine (450 mg) as white crystals. A solution of 2-(t-butoxycarbonyl)-4-(2-chlorophenyl)-5-cyano-4,7-dihydro-6-(morpholin-4-yl)methyl-2H-pyrazolo[3,4-b]pyridine (440 mg) in trifluoroacetic acid (5 ml) was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure and 4M hydrochloric acid-dioxane solution was added. The precipitated crystals were collected by filtration and washed with ethyl acetate to give the title compound (250 mg) as pale-yellow crystals.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe obtained residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate (2:1))
  3. customcrystallized from ethyl acetate

Sources & evidence

ORD record
ord-a2737c8ba96246fab2fcdb16118c0c1c
Source dataset
uspto-grants-2005_12
Patent number
US06977262B2

Reaction notes

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