6-Bromo-N-methylnicotinamide → N-Methyl-6-[7-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl]-nicotinamide

HRID 467578

Reaction equation

HRID 467578 reaction equation
[CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C@H:7]1[CH2:11][CH2:10][N:9]([C:12]2[CH:22]=[CH:21][C:15]3[CH2:16][CH2:17][NH:18][CH2:19][CH2:20][C:14]=3[CH:13]=2)[CH2:8]1.CC(C)([O-])C.[Na+].Br[C:30]1[CH:39]=[CH:38][C:33]([C:34]([NH:36][CH3:37])=[O:35])=[CH:32][N:31]=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:37][NH:36][C:34](=[O:35])[C:33]1[CH:38]=[CH:39][C:30]([N:18]2[CH2:19][CH2:20][C:14]3[CH:13]=[C:12]([N:9]4[CH2:10][CH2:11][C@H:7]([N:3]5[CH2:4][CH2:5][CH2:6][C@@H:2]5[CH3:1])[CH2:8]4)[CH:22]=[CH:21][C:15]=3[CH2:16][CH2:17]2)=[N:31][CH:32]=1

Participants

6

Reactant 3

HCID 230921426-Bromo-N-methylnicotinamideHCID 23676156Sodium t-butoxideHCID 546701937-((2S,3'S)-2-Methyl-1,3'-bipyrrolidinyl-1'-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine

Product 1

HCID 54670196N-Methyl-6-[7-((2S,3'S)-2-methyl-[1,3']bipyrrolidinyl-1'-yl)-1,2,4,5-tetrahydro-benzo[d]azepin-3-yl]-nicotinamideYield 92.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

7-((2S,3′S)-2-Methyl-1,3′-bipyrrolidinyl-1′-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine (150 mg, 0.50 mmol) was added to a mixture of tris(dibenzylideneacetone)-dipalladium (6.88 mg, 0.007), R-BINAP (22.5 mg, 0.022 mmol), sodium tert-butoxide (69.8 mg, 0.72 mmol) and 6-bromo-N-methyl-nicotinamide (118 mg, 0.55 mmol) in 6 mL of toluene and the mixture was degassed (vacuum, 3×). The reaction mixture was heated at 85° C. for 17 h, and then it was partitioned between ethyl acetate and water. The aqueous phase washed with ethyl acetate and then the organic layer was washed with brine, dried over magnesium sulfate, filtered and concentrated to leave 200 mg of an oil.

Workup

  1. customthe mixture was degassed (vacuum, 3×)
  2. customit was partitioned between ethyl acetate and water
  3. washThe aqueous phase washed with ethyl acetate
  4. washthe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-0144bbb5c2c44ed287786531d85ff0f2
Source dataset
uspto-grants-2014_01
Patent number
US08623877B2

Linked notes

Loading…