1,2-Dichloroethane → bis(1,1-dimethylethyl) (4-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)amino]carbonyl}-1H-imidazol-2-yl)imidodicarbonate

HRID 1875078ノート

反応式

HRID 1875078 の反応式
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]([Cl:23])=[CH:21][CH:22]=1.[CH3:35][C:36]([O:39][C:40]([N:42]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[C:43]1[NH:44][CH:45]=[C:46]([C:48](O)=[O:49])[N:47]=1)=[O:41])([CH3:38])[CH3:37].C(=O)(O)[O-].[Na+]>CN(C=O)C>[CH3:38][C:36]([O:39][C:40]([N:42]([C:43]1[NH:44][CH:45]=[C:46]([C:48]([NH:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([O:24][C:25]3[CH:26]=[C:27]([C:28]#[N:29])[CH:30]=[C:31]([Cl:33])[CH:32]=3)[C:18]=2[F:34])=[O:49])[N:47]=1)[C:51]([O:53][C:54]([CH3:55])([CH3:56])[CH3:57])=[O:52])=[O:41])([CH3:35])[CH3:37]

参加物

7

反応物 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 178454351HCID 178454351、化合物

生成物 1

HCID 178454350bis(1,1-dimethylethyl) (4-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)amino]carbonyl}-1H-imidazol-2-yl)imidodicarbonate

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

EDC (0.035 g, 0.183 mmol) and HOBT (0.025 g, 0.183 mmol) were added to a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.048 g, 0.153 mmol) and 2-(bis{[(1,1-dimethylethyl)oxy]carbonyl}amino)-1H-imidazole-4-carboxylic acid (0.050 g, 0.153 mmol) in DMF (2 mL). The mixture was stirred at RT overnight. Saturated aqueous sodium bicarbonate was added and the reaction mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated to give crude bis(1,1-dimethylethyl)(4-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)amino]carbonyl}-1H-imidazol-2-yl)imidodicarbonate as an oil. Trifluoroacetic acid (0.3 mL, 3.89 mmol) was added to a solution of bis(1,1-dimethylethyl)(4-{[({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)amino]carbonyl}-1H-imidazol-2-yl)imidodicarbonate (0.066 g, 0.106 mmol) in dichloromethane (2 mL). The mixture was stirred at RT overnight, concentrated and purified by reverse phase HPLC (acetonitrile:water with 0.1% formic acid) to give the title compound (0.017 g, 27%). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.09-8.18 (m, 2H), 7.81 (s, 1H), 7.51 (s, 1H), 7.44-7.50 (m, 2H), 7.30 (t, 1H), 7.10 (s, 1H), 5.45 (br. s., 2H), 4.44 (d, 2H). MS m/z 420 (M+1).

後処理

  1. extractionthe reaction mixture was extracted with ethyl acetate
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated

出典と根拠

ORDレコード
ord-ce8f0ccc4a9f4a3b846bbbfadfd0ab31
出典データセット
uspto-grants-2012_11
特許番号
US08304419B2

反応ノート

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