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

HRID 62661노트

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HRID 62661 반응식
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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 7237O-Xylene용매

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온도
100 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-f5d8ae6b18cc4fb39193805344825bf0
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447039B2

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