1,2-Dichloroethane → N-{2-[3-(4-Cyano-3-fluoro-benzyl)-2-methyl-3H-imidazol-4-yl]-ethyl}-5-hydroxy-2-iodobenzamide

HRID 278194Notes

Reaction equation

HRID 278194 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)[C:9]([CH3:21])=[N:8][CH:7]=1.[OH:22][C:23]1[CH:24]=[CH:25][C:26]([I:32])=[C:27]([CH:31]=1)[C:28](O)=[O:29].O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.C(Cl)CCl>CN(C=O)C.O>[C:16]([C:15]1[CH:18]=[CH:19][C:12]([CH2:11][N:10]2[C:6]([CH2:5][CH2:4][NH:3][C:28](=[O:29])[C:27]3[CH:31]=[C:23]([OH:22])[CH:24]=[CH:25][C:26]=3[I:32])=[CH:7][N:8]=[C:9]2[CH3:21])=[CH:13][C:14]=1[F:20])#[N:17]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 12380035-Hydroxy-2-iodobenzoic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 226271114-[5-(2-Amino-ethyl)-2-(methyl)-imidazol-1-ylmethyl]-2-fluoro-benzonitrile dihydrochloride

Product 1

HCID 22627100N-{2-[3-(4-Cyano-3-fluoro-benzyl)-2-methyl-3H-imidazol-4-yl]-ethyl}-5-hydroxy-2-iodobenzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A stirred mixture of 4-[5-(2-amino-ethyl)-2-(methyl)-imidazol-1-ylmethyl]-2-fluoro-benzonitrile dihydrochloride as prepared in Example 10, Step A (2.00 g, 6.038 mmol), 5-hydroxy-2-iodobenzoic acid (1.594 g, 6.038 mmol), 1-Hydroxybenzotriazole hydrate (816 mg, 6.038 mmol), and triethylamine (2.52 mL, 18.114 mmol) in dry DMF (12.0 mL) was cooled to 0° C., and EDC (1.158 g, 6.038 mmol) was added. After stirring at 0° C. for 15 minutes, the reaction mixture was stirred at ambient temperature overnight, then poured into water and extracted with EtOAc. The organic layer was dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was preabsorbed onto silica gel and purified by flash chromatography eluting with a gradient of 6-9% MeOH/CH2Cl2 to give the titled product.

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature overnight
  2. extractionextracted with EtOAc
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was preabsorbed onto silica gel
  7. custompurified by flash chromatography
  8. washeluting with a gradient of 6-9% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-daa550378134443d9e8c1621a78b7265
Source dataset
uspto-grants-2002_03
Patent number
US06358985B1

Reaction notes

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