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Diisopropylethylamine → 5-(Acetylamino)-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide

HRID 1874830
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HRID 1874830 반응식
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:25][CH2:26][C:27]1[C:28]([F:44])=[C:29]([O:34][C:35]2[CH:36]=[C:37]([CH:40]=[C:41]([Cl:43])[CH:42]=2)[C:38]#[N:39])[C:30]([Cl:33])=[CH:31][CH:32]=1.[C:45]([NH:48][C:49]1[CH:50]=[C:51]2[C:55](=[CH:56][CH:57]=1)[NH:54][C:53]([C:58](O)=[O:59])=[CH:52]2)(=[O:47])[CH3:46].CCN(C(C)C)C(C)C>CN(C=O)C>[C:45]([NH:48][C:49]1[CH:50]=[C:51]2[C:55](=[CH:56][CH:57]=1)[NH:54][C:53]([C:58]([NH:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([O:34][C:35]3[CH:36]=[C:37]([C:38]#[N:39])[CH:40]=[C:41]([Cl:43])[CH:42]=3)[C:28]=1[F:44])=[O:59])=[CH:52]2)(=[O:47])[CH3:46]
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참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 107751705-acetamido-1H-indole-2-carboxylic AcidHCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile

생성물 1

HCID 59451512
5-(Acetylamino)-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide
수율 43%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

HATU (0.023 g, 0.062 mmol) was added to a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.013 g, 0.041 mmol), 5-(acetylamino)-1H-indole-2-carboxylic acid (0.009 g, 0.041 mmol) and DIPEA (0.011 mL, 0.062 mmol) in DMF (0.5 mL). The reaction mixture was stirred at RT overnight and was extracted with ethyl acetate and water. The organic layer was washed with brine, dried over sodium sulfate and concentrated. The residue was triturated with methanol to give the title compound (0.009 g, 43%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.50 (s, 1H), 9.74 (s, 1H), 8.95 (s, 1H), 7.91 (s, 1H), 7.78 (s, 1H), 7.40-7.49 (m, 3H), 7.32-7.40 (m, 1H), 7.28 (s, 1H), 7.15-7.24 (m, 1H), 7.06 (s, 1H), 4.53 (s, 2H), 1.98 (s, 3H). MS: m/z 511 (M+1).

후처리

  1. extractionwas extracted with ethyl acetate and water
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was triturated with methanol

출처 및 근거

ORD 기록
ord-eb61922c2623432b8b9b9ad6e712411a
출처 데이터셋
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08304419B2

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