Ethyl 2-chloroethanecarboximidate hydrochloride → HCID 22380063、化合物

HRID 895512ノート

反応式

HRID 895512 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[NH:10][CH2:11][CH2:12][CH3:13])[C:5]#[N:6].Cl.[Cl:15][CH2:16][C:17](=N)OCC>C(O)C>[ClH:15].[CH2:11]([N:10]1[C:9]2[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[CH:3][C:2]=2[N:1]=[C:17]1[CH2:16][Cl:15])[CH2:12][CH3:13]

参加物

4

反応物 2

HCID 12470659Ethyl 2-chloroethanecarboximidate hydrochlorideHCID 223802993-Amino-4-(propylamino)benzonitrile

生成物 1

HCID 22380063HCID 22380063、化合物

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

A solution of 3-amino-4-n-propylaminobenzonitrile (7.38 g, 42.1 mmol) and ethyl chloroacetimidate hydrochloride (9.92 g, 63.2 mmol) in ethanol (100 mL) is heated at reflux for 17 h, then cooled and concentrated to give 1-n-Propyl-2-chloromethyl-5-cyanobenzimidazole hydrochloride. Prior to use in the next step, this material is converted to free base by adding aqueous bicarbonate and extracting with dichloromethane, drying (Na2SO4), and concentrating. ii) Alternatively, chloroacetylchloride rather than ethyl chloroacetimidate can by used: To a solution of 3-amino-4-n-propylaminobenzonitrile (5.15 g, 29.4 mmol) and triethylamine (4.51 mL) in ethyl acetate (52 mL) at room temperature, chloroacetyl chloride (2.57 mL) is added slowly. After stirring the reaction mixture for 30 minutes at room temperature, acetic acid (5 mL) is added and the reaction mixture heated to reflux. After heating for 20 h, the reaction mixture is cooled to room temperature and diluted with water (50 mL). The organic solution is washed twice with 1.0 M sodium hydroxide (2×50 mL), then washed with an aqueous solution of 0.25 M KH2PO4 (50 mL), followed by brine (50 mL). The organic layer is dried (sodium sulfate), concentrated in vacuo, and the solid recrystallized by heating in ethyl acetate (20 mL), adding hexane (40 mL) and cooling to room temperature with stirring to afford 1-n-Propyl-2-chloromethyl-5-cyanobenzimidazole as brown crystals. 1H NMR (CDCl3): δ 8.08 (d, J=0.8 Hz, 1H), 7.57 (dd, J=1.65, 8.52 Hz, 1H), 7.45 (d, J=8.24 Hz, 1H), 7.26 (s, 1H), 4.84 (s, 2H), 4.24 (t, J=7.6 Hz, 2H), 1.94 (pentet, J=7.4. 7.6 Hz, 2H), 1.03 (t, J=7.4 Hz, 3H). (B) Preparation of 1-Propyl-2-{([2-(2-fluoropyrid-6-yl)-1H-imidazol-1-yl]methyl}-5-cyano-1H-benzimidazole

後処理

  1. temperatureat reflux for 17 h
  2. temperaturecooled
  3. concentrationconcentrated

出典と根拠

ORDレコード
ord-8d5311780ec94faf846ceaba557a9d73
出典データセット
uspto-grants-2005_07
特許番号
US06916819B2

反応ノート

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