Tetrahydrofuran → N-(4-Chloro-2-cyanophenyl)-2-(5-morpholin-4ylbenzimidazol-2-yl)acetamide

HRID 1169999

反応式

HRID 1169999 の反応式
[Li+].C[Si]([N-:6][Si](C)(C)C)(C)C.N1(CCO[C:20]2[CH:34]=[CH:33][C:23]3[N:24]=[C:25]([CH2:27][C:28]([O:30]CC)=O)[NH:26][C:22]=3[CH:21]=2)CCOCC1.[NH2:35][C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][C:37]=1[C:43]#[N:44].[CH2:45]1[CH2:49][O:48][CH2:47][CH2:46]1>>[Cl:42][C:39]1[CH:40]=[CH:41][C:36]([NH:35][C:28](=[O:30])[CH2:27][C:25]2[NH:26][C:22]3[CH:21]=[C:20]([N:6]4[CH2:45][CH2:49][O:48][CH2:47][CH2:46]4)[CH:34]=[CH:33][C:23]=3[N:24]=2)=[C:37]([C:43]#[N:44])[CH:38]=1

参加物

5

反応物 4

HCID 8028Tetrahydrofuran2 回HCID 800192-Amino-5-chlorobenzonitrileHCID 2733832Lithium HexamethyldisilazideHCID 12988786Ethyl 2-[5-(2-morpholin-4-ylethoxy)benzimidazol-2-yl]acetate

生成物 1

HCID 22664809N-(4-Chloro-2-cyanophenyl)-2-(5-morpholin-4ylbenzimidazol-2-yl)acetamide

反応条件

温度
23 °C

実験手順

LiHMDS (2.5 equivalents) was added to ethyl 2-[5-(2-morpholin-4-ylethoxy)benzimidazol-2-yl]acetate (1.0 equivalent) in THF at −78° C. After 1 hour, 2-amino-5-chlorobenzenecarbonitrile (0.82 equivalents) in THF was added. The reaction was allowed to warm to 23° C. and stirred overnight. The resulting mixture was quenched with NH4Cl (aqueous saturated solution) and extracted with EtOAc. The combined organic layers were washed with H2O and brine, dried over Na2SO4, filtered and concentrated in vacuo to yield a brown solid. The crude material was purified by silica gel chromatography (5:1 EtOAc:hexane) to give the desired product. LC/MS m/z 396.1 (MH+), Rt 1.79 minutes. N-(4-chloro-2-cyanophenyl)-2-(5-morpholin-4-ylbenzimidazol-2-yl)acetamide (1.0 equivalent) was heated in NaOMe (0.5 M in MeOH, 18 equivalents) at 70° C. for 2 hours. The resulting mixture was cooled, and the resulting solid was filtered and washed with water to give the desired product. LC/MS m/z 396.4 (MH+), Rt 2.13 minutes.

後処理

  1. customThe resulting mixture was quenched with NH4Cl (aqueous saturated solution)
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with H2O and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto yield a brown solid
  8. customThe crude material was purified by silica gel chromatography (5:1 EtOAc:hexane)

出典と根拠

ORDレコード
ord-3ab56f3367944826ac2cdc21c82ac10a
出典データセット
uspto-grants-2010_11
特許番号
US07825132B2

関連ノート

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