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

HRID 2377835

Reaction equation

HRID 2377835 reaction equation
[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

Participants

5

Reactant 4

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

Product 1

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

Conditions

Temperature
23 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-b70296c9cad54b4f8e4823cbaf0162c1
Source dataset
uspto-grants-2008_12
Patent number
US07470709B2

Linked notes

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