1,2-Dichloroethane → HCID 178436403、化合物

HRID 1875103ノート

反応式

HRID 1875103 の反応式
[NH2:1][CH2:2][C:3]1[C:4]([F:21])=[C:5]([O:11][C:12]2[CH:13]=[C:14]([CH:17]=[C:18]([Cl:20])[CH:19]=2)[C:15]#[N:16])[C:6]([CH2:9][CH3:10])=[CH:7][CH:8]=1.[N:22]([C:25]1[NH:26][C:27]([C:31](O)=[O:32])=[C:28]([Cl:30])[N:29]=1)=[N+]=[N-].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C([O-])(O)=O.[Na+]>CN(C=O)C.[Pd].CC([O-])=O.CC([O-])=O.[Pb+2].C(OCC)(=O)C>[NH2:22][C:25]1[NH:26][C:27]([C:31]([NH:1][CH2:2][C:3]2[CH:8]=[CH:7][C:6]([CH2:9][CH3:10])=[C:5]([O:11][C:12]3[CH:13]=[C:14]([C:15]#[N:16])[CH:17]=[C:18]([Cl:20])[CH:19]=3)[C:4]=2[F:21])=[O:32])=[C:28]([Cl:30])[N:29]=1

参加物

9

反応物 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 68487595HCID 68487595、化合物HCID 1785145302-azido-4-chloro-1H-imidazole-5-carboxylic acid

生成物 1

HCID 178436403HCID 178436403、化合物収率 53.5%

試薬・触媒・溶媒 3

HCID 131709914Lindlars catalyst触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒2 回

実験手順

A solution of 3-{[3-(aminomethyl)-6-ethyl-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.075 g, 0.246 mmol), 2-azido-4-chloro-1H-imidazole-5-carboxylic acid (0.051 g, 0.271 mmol), EDC (0.052 g, 0.271 mmol) and HOBT (0.041 g, 0.271 mmol) in DMF (4 ml) was stirred at RT under an atmosphere of nitrogen for 16 h then ethyl acetate (100 mL) and saturated aqueous NaHCO3 solution (100 mL) were added. The organic layer was separated, washed with saturated aqueous NaHCO3 solution (100 mL), water (100 mL), dried over MgSO4, filtered and concentrated. Ethyl acetate (20 mL) and Lindlar Catalyst (0.026 g, 0.247 mmol) were added and the mixture was stirred at RT under an atmosphere of hydrogen (55 psig) for 19 h. The vessel was carefully vented and the mixture was filtered thru Celite, concentrated purified by Reverse Phase HPLC (MeCN/water+0.1% TFA) to give the title compound (0.059 g, 51%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.93 (s, 1H), 7.77 (t, 1H), 7.70 (t, 1H), 7.39 (s, 1H), 7.33 (t, 1H), 7.18-7.29 (m, 2H), 5.81 (s, 2H), 4.47 (d, 2H), 2.47-2.54 (m, 2H), 1.08 (t, 3H). LCMS m/z 450.1 (M+H).

後処理

  1. customThe organic layer was separated
  2. washwashed with saturated aqueous NaHCO3 solution (100 mL), water (100 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. filtrationthe mixture was filtered thru Celite
  7. concentrationconcentrated
  8. custompurified by Reverse Phase HPLC (MeCN/water+0.1% TFA)

出典と根拠

ORDレコード
ord-8fffd20813c0484385012115ad9f9977
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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