Triethylamine → N-[2-({2-[3-(4-cyano-3-fluoro-benzyl)-3H-imidazol-4-yl]-ethylamino}-methyl)-phenyl]-3-hydroxy-benzamide

HRID 278193Notes

Reaction equation

HRID 278193 reaction equation
Cl.Cl.[NH2:3][CH2:4][CH2:5][C:6]1[N:10]([CH2:11][C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[C:14]([F:20])[CH:13]=2)[CH:9]=[N:8][CH:7]=1.CCN(CC)CC.[CH:28]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[NH:36][C:37](=[O:45])[C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([OH:44])[CH:39]=1)=O.[BH3-]C#N.[Na+]>CO>[C:16]([C:15]1[CH:18]=[CH:19][C:12]([CH2:11][N:10]2[C:6]([CH2:5][CH2:4][NH:3][CH2:28][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[NH:36][C:37](=[O:45])[C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([OH:44])[CH:39]=3)=[CH:7][N:8]=[CH:9]2)=[CH:13][C:14]=1[F:20])#[N:17]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 5003444Sodium cyanoborohydrideHCID 22627093N-(2-formyl-phenyl)-3-hydroxy-benzamideHCID 226271054-[5-(2-Amino-ethyl)-imidazol-1-ylmethyl]-2-fluoro-benzonitrile dihydrochloride

Product 1

HCID 22627116N-[2-({2-[3-(4-cyano-3-fluoro-benzyl)-3H-imidazol-4-yl]-ethylamino}-methyl)-phenyl]-3-hydroxy-benzamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 4-[5-(2-amino-ethyl)-imidazol-1-ylmethyl]-2-fluoro-benzonitrile dihydrochloride (Step F) (0.64 g, 2.03 mmol) in MeOH (15 mL) was added NEt3 dropwise to pH=4.5. To this solution was added N-(2-formyl-phenyl)-3-hydroxy-benzamide (0.64 g, 2.64 mmol) and NaCNBH3 (0.255 g, 4.06 mmol), and the reaction was stirred 18 h at 25° C. The MeOH was removed in vacuo, and the residue was partitioned with EtOAc and saturated NaHCO3. The organic layer was separated and washed 3× with 10% HCl. The acidic layers were combined, made basic with Na2CO3, then extracted 3× with EtOAc. These layers were combined, washed with brine and dried (MgSO4). Filtration and concentration in vacuo gave the crude product which was purified by prep HPLC to obtain the title compound.

Workup

  1. customThe MeOH was removed in vacuo
  2. customthe residue was partitioned with EtOAc and saturated NaHCO3
  3. customThe organic layer was separated
  4. washwashed 3× with 10% HCl
  5. extractionextracted 3× with EtOAc
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationFiltration and concentration in vacuo
  9. customgave the crude product which
  10. customwas purified by prep HPLC

Sources & evidence

ORD record
ord-bc6629a8dce643dcb696410e69f76743
Source dataset
uspto-grants-2002_03
Patent number
US06358985B1

Reaction notes

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