Aniline → 4-methyl-N-((1R,2S)-2-methylcyclohexyl)-6-(phenylamino)-1H-indole-2-carboxamide

HRID 62661ノート

反応式

HRID 62661 の反応式
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([NH:13][C@@H:14]3[CH2:19][CH2:18][CH2:17][CH2:16][C@@H:15]3[CH3:20])=[O:12])[NH:8]2)=[C:4]([CH3:21])[CH:3]=1.CC(P(C(C)(C)C)C1C(C2C=CC=CC=2)=CC=CC=1)(C)C.C(O[K])(C)(C)C.[NH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1>C1(C)C(C)=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:21][C:4]1[CH:3]=[C:2]([NH:49][C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[CH:10]=[C:9]2[C:5]=1[CH:6]=[C:7]([C:11]([NH:13][C@@H:14]1[CH2:19][CH2:18][CH2:17][CH2:16][C@@H:15]1[CH3:20])=[O:12])[NH:8]2

参加物

7

反応物 4

HCID 6115AnilineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 732918016-bromo-4-methyl-N-((1R,2S)-2-methylcyclohexyl)-1H-indole-2-carboxamideHCID 178418922HCID 178418922、化合物

生成物 1

HCID 735079534-methyl-N-((1R,2S)-2-methylcyclohexyl)-6-(phenylamino)-1H-indole-2-carboxamide収率 31%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 7237O-Xylene溶媒

反応条件

温度
100 °C

実験手順

To a stirred solution of 6-bromo-4-methyl-N-((1R,2S)-2-methylcyclohexyl)-1H-indole-2-carboxamide (4AH: 500 mg, 1.43 mmol) in xylene (7.5 mL) were added Pd(OAc)2 (58 mg, 0.26 mmol), JohnPhos (51 mg, 0.17 mmol), tBuOK (644 mg, 5.74 mmol) and aniline (802 mg, 8.62 mmol). The resulting mixture was purged with argon for 10 minutes and then heated at 100° C. for 3 h in sealed tube. The reaction mixture was partitioned between ethyl acetate and water. The organic layer separated and washed with brine and dried over Na2SO4, concentrated. The crude product was purified by column chromatography followed by preparative HPLC to obtain 160 mg of 4-methyl-N-((1R,2S)-2-methylcyclohexyl)-6-(phenylamino)-1H-indole-2-carboxamide (6A: 30%) as an off-white solid.

後処理

  1. customThe resulting mixture was purged with argon for 10 minutes
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. customThe organic layer separated
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography

出典と根拠

ORDレコード
ord-f5d8ae6b18cc4fb39193805344825bf0
出典データセット
uspto-grants-2016_09
特許番号
US09447039B2

反応ノート

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