1,2-Dichloroethane → N-(3'-hydroxybiphenyl-2-ylmethyl)-2-[3-(4-cyano-3-fluorobenzyl)-3H-imidazol-4-yl]acetamide

HRID 278176Notes

Reaction equation

HRID 278176 reaction equation
[C:1]([C:3]1[CH:18]=[CH:17][C:6]([CH2:7][N:8]2[C:12]([CH2:13][C:14]([O-:16])=O)=[CH:11][N:10]=[CH:9]2)=[CH:5][C:4]=1[F:19])#[N:2].[Li+].Cl.[NH2:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([OH:36])[CH:31]=1.O.ON1C2C=CC=CC=2N=N1.C(Cl)CCl.C(N(C(C)C)CC)(C)C>>[OH:36][C:32]1[CH:31]=[C:30]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=2[CH2:23][NH:22][C:14](=[O:16])[CH2:13][C:12]2[N:8]([CH2:7][C:6]3[CH:17]=[CH:18][C:3]([C:1]#[N:2])=[C:4]([F:19])[CH:5]=3)[CH:9]=[N:10][CH:11]=2)[CH:35]=[CH:34][CH:33]=1

Participants

6

Reactant 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 226270902-Aminomethyl-3'-hydroxybiphenyl hydrochlorideHCID 23702864Lithium 1-(4-cyano-3-fluorobenzyl)-imidazol-5-ylacetate

Product 1

HCID 22627115N-(3'-hydroxybiphenyl-2-ylmethyl)-2-[3-(4-cyano-3-fluorobenzyl)-3H-imidazol-4-yl]acetamide

Procedure

A solution of lithium 1-(4-cyano-3-fluorobenzyl)imidazol-5-ylacetate from Step D (143 mg, 0.55 mmol), 2-aminomethyl-3′-hydroxybiphenyl hydrochloride from Example 4, Step H (118 mg, 0.50 mmol), 1-hydroxybenzotriazole hydrate (74 mg, 0.55 mmol), EDC (105 mg, 0.55 mmol), and diisopropylethylamine (129 mg, 1.00 mmol) in dry, degassed DMF (2 mL) was stirred at ambient temperature overnight. The solvent was removed under reduced pressure and the residue was partitioned between sat. aq. NaHCO3 (3 mL) and CHCl3 (5 mL). The aqueous layer was extracted further with CHCl3 (2×5 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography, eluting with a gradient of 3-5% MeOH/0.3-0.5% NH4OH in CHCl3 to give the titled product as a white foam.

Workup

  1. customdegassed DMF (2 mL)
  2. customThe solvent was removed under reduced pressure
  3. customthe residue was partitioned between sat. aq. NaHCO3 (3 mL) and CHCl3 (5 mL)
  4. extractionThe aqueous layer was extracted further with CHCl3 (2×5 mL)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash column chromatography
  9. washeluting with a gradient of 3-5% MeOH/0.3-0.5% NH4OH in CHCl3

Sources & evidence

ORD record
ord-a5bcbe1a98764649acf60c44e5930d77
Source dataset
uspto-grants-2002_03
Patent number
US06358985B1

Reaction notes

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