1,2-Dichloroethane → 2-{5-[1-(4-cyano-3-fluorophenyl)-1-hydroxyethyl]imidazol-1-yl}-N-[2-(3'-hydroxybiphenyl-2-yl)ethyl]acetamide

HRID 278186Notes

Reaction equation

HRID 278186 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:12]2[N:16]([CH2:17][C:18]([OH:20])=O)[CH:15]=[N:14][CH:13]=2)([OH:11])[CH3:10])=[CH:5][C:4]=1[F:21])#[N:2].[Li].[NH2:23][CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([OH:38])[CH:33]=1.O.ON1C2C=CC=CC=2N=N1.C(Cl)CCl.C(N(CC)C(C)C)(C)C>>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:12]2[N:16]([CH2:17][C:18]([NH:23][CH2:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([OH:38])[CH:33]=3)=[O:20])[CH:15]=[N:14][CH:13]=2)([OH:11])[CH3:10])=[CH:5][C:4]=1[F:21])#[N:2]

Participants

7

Reactant 6

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 3028194LithiumHCID 18433492{5-[1-(4-Cyano-3-fluorophenyl)-1-hydroxyethyl]imidazol-1-yl}acetic acidHCID 226270861-Amino-2-(3'-hydroxybiphenyl-2-yl)ethane

Product 1

HCID 226270892-{5-[1-(4-cyano-3-fluorophenyl)-1-hydroxyethyl]imidazol-1-yl}-N-[2-(3'-hydroxybiphenyl-2-yl)ethyl]acetamide

Procedure

A solution of {5-[1-(4-cyano-3-fluorophenyl)-1-hydroxyethyl]imidazol-1-yl}acetic acid, lithium salt from Step H (40 mg, 0.145 mmol), 1-amino-2-(3′-hydroxybiphenyl-2-yl)ethane from Example 6, Step C (33 mg, 0.155 mmol), 1-hydroxybenzotriazole hydrate (23 mg, 0.17 mmol), EDC (33 mg, 0.17 mmol), and N,N-diisopropylethylamine (40 mg, 0.31 mmol) in dry, degassed DMF (1 mL) was stirred at ambient temperature for 18 hrs. The solvent was removed under reduced pressure and the residue was partitioned between sat. aq. NaHCO3 (1 mL) and CHCl3 (3 mL). The aqueous layer was extracted further with CHCl3 (2×2 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified by preparative thin layer chromatography, eluting with 6% MeOH/0.6% NH4OH in CH2Cl2 to give the titled product as a white solid.

Workup

  1. customdegassed DMF (1 mL)
  2. customThe solvent was removed under reduced pressure
  3. customthe residue was partitioned between sat. aq. NaHCO3 (1 mL) and CHCl3 (3 mL)
  4. extractionThe aqueous layer was extracted further with CHCl3 (2×2 mL)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by preparative thin layer chromatography
  9. washeluting with 6% MeOH/0.6% NH4OH in CH2Cl2

Sources & evidence

ORD record
ord-b800d3e8c43f40e8aa95bdd84415451c
Source dataset
uspto-grants-2002_03
Patent number
US06358985B1

Reaction notes

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