2-Aminobenzimidazole → n-(1h-Benzoimidazol-2-yl)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide

HRID 1018828Notes

Reaction equation

HRID 1018828 reaction equation
F[P-](F)(F)(F)(F)F.[N:8]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[N:10]=N1.C1(C[C@H](N2CC3C(=CC=CC=3)C2=O)C(O)=O)CCCCC1.NC1NC2C=CC=CC=2N=1.[CH:59]1([CH2:65][C@H:66]([N:75]2[CH2:83][C:82]3[C:77](=[CH:78][CH:79]=[CH:80][CH:81]=3)[C:76]2=[O:84])[C:67]([NH:69][C:70]2SC=CN=2)=[O:68])[CH2:64][CH2:63][CH2:62][CH2:61][CH2:60]1>>[NH:10]1[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[N:8]=[C:70]1[NH:69][C:67](=[O:68])[CH:66]([N:75]1[CH2:83][C:82]2[C:77](=[CH:78][CH:79]=[CH:80][CH:81]=2)[C:76]1=[O:84])[CH2:65][CH:59]1[CH2:64][CH2:63][CH2:62][CH2:61][CH2:60]1

Participants

5

Reactant 4

HCID 136242-AminobenzimidazoleHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 1477119(S)-3-Cyclohexyl-2-(1-oxoisoindolin-2-yl)propanoic acidHCID 9947513(S)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide

Product 1

HCID 18402226n-(1h-Benzoimidazol-2-yl)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamideYield 60%

Procedure

This compound was prepared via BOP coupling of (S)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (prepared in Example 1, Step A, 287 mg; 1.0 mmol and 2-amino-benzimidazole (119 mg; 1.0 mmol) in a manner similar to that used for the preparation of (S)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-N-thiazol-2-yl-propionamide (outlined in Example 9, Step B) to provide crude N-(5-Bromo-thiazol-2-yl)-3-cyclohexyl-2-(5,6-dichloro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide. The crude product was purified by reverse-phase HPLC (Rainin Dynamax SD-1 instrument) using a gradient of 10% acetonitrile/water/0.1% trifluoroacetic acid to 100% acetonitrile on a C18 column. The combined fractions containing product were concentrated to remove most of the acetonitrile and then extracted with ethyl acetate. The extracts were dried (sodium sulfate) and concentrated in vacuo to give 240 mg (60%) of N-(1H-Benzoimidazol-2-yl)-3-cyclohexyl-2-(1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide as a white solid: EI-HRMS m/e calcd for C24H26N4O2 (M+) 402.2056, found 402.2056.

Workup

  1. customprepared in Example 1, Step A, 287 mg
  2. customto provide crude N-(5-Bromo-thiazol-2-yl)-3-cyclohexyl-2-(5,6-dichloro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionamide
  3. customThe crude product was purified by reverse-phase HPLC (Rainin Dynamax SD-1 instrument)
  4. additionThe combined fractions containing product
  5. concentrationwere concentrated
  6. customto remove most of the acetonitrile
  7. extractionextracted with ethyl acetate
  8. dry with materialThe extracts were dried (sodium sulfate)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-39d1fcfef04e40f7a4278541100c9a8e
Source dataset
uspto-grants-2002_11
Patent number
US06482951B2

Reaction notes

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