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

反応式

HRID 467578 の反応式
[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

参加物

6

反応物 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

生成物 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]-nicotinamide収率 92.3%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
85 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-0144bbb5c2c44ed287786531d85ff0f2
出典データセット
uspto-grants-2014_01
特許番号
US08623877B2

関連ノート

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