Diisopropylethylamine → 6-acetamido-N-[[4-chloro-3-(3-chloro-5-cyanophenoxy)-2-fluorophenyl]methyl]-1H-indole-2-carboxamide

HRID 1874832노트

반응식

HRID 1874832 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:57]=[C:56]2[C:52]([CH:53]=[C:54]([C:58](O)=[O:59])[NH:55]2)=[CH:51][CH:50]=1)(=[O:47])[CH3:46].CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C.O>[C:45]([NH:48][C:49]1[CH:57]=[C:56]2[C:52]([CH:53]=[C:54]([C:58]([NH:25][CH2:26][C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([O:34][C:35]4[CH:36]=[C:37]([C:38]#[N:39])[CH:40]=[C:41]([Cl:43])[CH:42]=4)[C:28]=3[F:44])=[O:59])[NH:55]2)=[CH:51][CH:50]=1)(=[O:47])[CH3:46]

참가 물질

8

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 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 594515286-(acetylamino)-1H-indole-2-carboxylic acid

생성물 1

HCID 594513686-acetamido-N-[[4-chloro-3-(3-chloro-5-cyanophenoxy)-2-fluorophenyl]methyl]-1H-indole-2-carboxamide수율 31.1%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

HATU (0.086 g, 0.227 mmol) was added to a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.047 g, 0.151 mmol), 6-(acetylamino)-1H-indole-2-carboxylic acid (0.033 g, 0.151 mmol) and DIPEA (0.040 mL, 0.227 mmol) in DMF (1 mL). The mixture was stirred at RT for 2 h. The reaction mixture was diluted with ethyl acetate and water. The organic layer was washed with water and dried over sodium sulfate, and the solvent was evaporated. The resulting oil was triturated with methylene chloride:methanol. The resulting solid was collected by filtration and dried under vacuum to give the title compound (0.024 g, 31%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.46 (s, 1H), 9.85 (s, 1H), 9.01 (m, 1H), 7.91 (s, 1H), 7.80 (s, 1H), 7.40-7.53 (m, 4H), 7.35 (t, 1H), 7.11 (m, 2H), 4.51 (d, 2H), 2.00 (s, 3H). MS: m/z 511 (M+1).

후처리

  1. washThe organic layer was washed with water
  2. dry with materialdried over sodium sulfate
  3. customthe solvent was evaporated
  4. customThe resulting oil was triturated with methylene chloride
  5. filtrationThe resulting solid was collected by filtration
  6. customdried under vacuum

출처 및 근거

ORD 기록
ord-5347ad5473ab4068a56eb85e79767c30
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08304419B2

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