1,2-Dichloroethane → 4-bromo-N-({4-bromo-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-imidazole-5-carboxamide

HRID 1875251노트

반응식

HRID 1875251 반응식
C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[NH2:15][CH2:16][C:17]1[C:18]([F:34])=[C:19]([O:24][C:25]2[CH:26]=[C:27]([CH:30]=[C:31]([Cl:33])[CH:32]=2)[C:28]#[N:29])[C:20]([Br:23])=[CH:21][CH:22]=1.[Br:35][C:36]1[N:37]=[CH:38][NH:39][C:40]=1[C:41](O)=[O:42]>CN(C=O)C>[Br:35][C:36]1[N:37]=[CH:38][NH:39][C:40]=1[C:41]([NH:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([Br:23])=[C:19]([O:24][C:25]2[CH:26]=[C:27]([C:28]#[N:29])[CH:30]=[C:31]([Cl:33])[CH:32]=2)[C:18]=1[F:34])=[O:42]

참가 물질

6

반응물 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 671971663-{[3-(Aminomethyl)-6-bromo-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 1785249144-bromo-1H-imidazole-5-carboxylic acid

생성물 1

HCID 1785099064-bromo-N-({4-bromo-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-imidazole-5-carboxamide수율 45.8%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

EDC (0.059 g, 0.309 mmol) and HOBT (0.042 g, 0.309 mmol) were added to a solution of 3-{[3-(aminomethyl)-6-bromo-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.100 g, 0.281 mmol) and 4-bromo-1H-imidazole-5-carboxylic acid (0.054 g, 0.281 mmol) in DMF (2 ml). The mixture was stirred at RT overnight. The reaction mixture was extracted with ethyl acetate and saturated aqueous sodium bicarbonate and the organic layer was dried over sodium sulfate and concentrated. Purification by reverse phase HPLC (acetonitrile:water with 0.1% formic acid) gave 0.068 g (45%) of the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.34 (br. s., 1H), 7.77 (s, 2H), 7.58 (d, 1H), 7.45 (s, 1H), 7.40 (t, 1H), 7.27 (t, 1H), 4.45 (d, 2H). ES MS: m/z 527 (M+1).

후처리

  1. extractionThe reaction mixture was extracted with ethyl acetate and saturated aqueous sodium bicarbonate
  2. dry with materialthe organic layer was dried over sodium sulfate
  3. concentrationconcentrated
  4. customPurification by reverse phase HPLC (acetonitrile:water with 0.1% formic acid)

출처 및 근거

ORD 기록
ord-aa4658bbf3914063afc5981facc299f5
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08304419B2

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