1,2-Dichloroethane → HCID 178509915、化合物

HRID 1875105ノート

反応式

HRID 1875105 の反応式
[NH2:1][CH2:2][C:3]1[C:4]([F:22])=[C:5]([O:12][C:13]2[CH:14]=[C:15]([CH:18]=[C:19]([Cl:21])[CH:20]=2)[C:16]#[N:17])[C:6]([CH:9]([F:11])[F:10])=[CH:7][CH:8]=1.[Cl:23][C:24]1[N:25]=[CH:26][N:27](COCC[Si](C)(C)C)[C:28]=1[C:29](O)=[O:30].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C([O-])(O)=O.[Na+].C(O)(C(F)(F)F)=O>CN(C=O)C.ClCCl.C(OCC)(=O)C>[Cl:23][C:24]1[N:25]=[CH:26][NH:27][C:28]=1[C:29]([NH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([F:11])[F:10])=[C:5]([O:12][C:13]2[CH:14]=[C:15]([C:16]#[N:17])[CH:18]=[C:19]([Cl:21])[CH:20]=2)[C:4]=1[F:22])=[O:30]

参加物

10

反応物 6

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 684803913-{[3-(Aminomethyl)-6-(difluoromethyl)-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 684855334-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid

生成物 1

HCID 178509915HCID 178509915、化合物収率 30.5%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A solution of 3-{[3-(aminomethyl)-6-(difluoromethyl)-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.08 g, 0.245 mmol), 4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid (0.068 g, 0.245 mmol), EDC (0.047 g, 0.245 mmol) and HOBT (0.037 g, 0.245 mmol) in DMF (4 ml) was stirred at RT under an atmosphere of nitrogen for 16 h then ethyl acetate (30 mL) and saturated aqueous NaHCO3 solution (30 mL) were added. The organic layer was separated, washed with saturated aqueous NaHCO3 solution (30 mL), water (30 mL), brine (30 mL), dried over MgSO4, filtered and concentrated. A solution of this residue and TFA (0.019 ml, 0.246 mmol) in dichloromethane (10 ml) was stirred at RT under an atmosphere of nitrogen for 16 h. The solvent was removed under vacuum and the resulting oil was purified by Reverse Phase HPLC (MeCN/water+0.1% TFA). The desired compound was washed with saturated aqueous NaHCO3 solution (25 mL) and extracted with ethyl acetate (25 mL). The organic layer was separated, washed with water (25 mL), brine (25 mL), dried over MgSO4, filtered and concentrated to give the title compound (0.034 g, 30%) as a white powder. 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.73 (s, 1H), 7.44-7.63 (m, 3H), 7.27 (d, 2H), 6.92 (t, 1H), 4.70 (s, 2H). LC/MS m/z 453.2 (M−H).

後処理

  1. customThe organic layer was separated
  2. washwashed with saturated aqueous NaHCO3 solution (30 mL), water (30 mL), brine (30 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe solvent was removed under vacuum
  7. customthe resulting oil was purified by Reverse Phase HPLC (MeCN/water+0.1% TFA)
  8. washThe desired compound was washed with saturated aqueous NaHCO3 solution (25 mL)
  9. extractionextracted with ethyl acetate (25 mL)
  10. customThe organic layer was separated
  11. washwashed with water (25 mL), brine (25 mL)
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated

出典と根拠

ORDレコード
ord-d5aaa45e075346249a8b06225adec923
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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