1,2-Dichloroethane → (R)-2-{5-[1-(4-cyano-3-fluorophenyl)-1-hydroxyethyl]imidazol-1-yl}-N-(1-(7-hydroxynaphthalen-1-yl)-2-oxopyrrolidin-3-yl)acetamide

HRID 2306218Notes

Reaction equation

HRID 2306218 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].Cl.[NH2:24][C@@H:25]1[CH2:29][CH2:28][N:27]([C:30]2[C:39]3[C:34](=[CH:35][CH:36]=[C:37]([OH:40])[CH:38]=3)[CH:33]=[CH:32][CH:31]=2)[CH2:26]1.O.[OH:42]N1C2C=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:24][C@@H:25]3[CH2:29][CH2:28][N:27]([C:30]4[C:39]5[C:34](=[CH:35][CH:36]=[C:37]([OH:40])[CH:38]=5)[CH:33]=[CH:32][CH:31]=4)[C:26]3=[O:42])=[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 70170706(R)-3-amino-1-[7-hydroxynaphthalen-1-yl]pyrrolidine hydrochloride

Product 1

HCID 70170714(R)-2-{5-[1-(4-cyano-3-fluorophenyl)-1-hydroxyethyl]imidazol-1-yl}-N-(1-(7-hydroxynaphthalen-1-yl)-2-oxopyrrolidin-3-yl)acetamide

Procedure

A solution of {5-[1-(4-cyano-3-fluorophenyl)-1-hydroxyethyl]imidazol-1-yl}acetic acid, lithium salt, as described above in Step E, (40 mg, 0.136 mmol), (R)-3-amino-1-[7-hydroxynaphthalen-1-yl]pyrrolidine hydrochloride, as described in Example 29, Step J, (42 mg, 0.151 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 hours. The solvent was removed under reduced pressure and the residue was partitioned between saturated aqueous 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 a gradient of CH2Cl2—6% MeOH—0.6% NH4OH to give the titled product.

Workup

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

Sources & evidence

ORD record
ord-435a70b7e24f4c3ea5b03692325b75d8
Source dataset
uspto-grants-2002_08
Patent number
US06441017B1

Reaction notes

Loading…