1,2-Dichloroethane → (+/-)-6-[4-(2-Phenyl-pyrrolidin-1-ylmethyl)-phenoxy]-nicotinamide hydrochloride

HRID 130765

Reaction equation

HRID 130765 reaction equation
[CH:1]([C:3]1[CH:18]=[CH:17][C:6]([O:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=2)=[CH:5][CH:4]=1)=O.[C:19]1([CH:25]2[CH2:29][CH2:28][CH2:27][NH:26]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C.[Cl:48]CCCl>>[ClH:48].[C:19]1([CH:25]2[CH2:29][CH2:28][CH2:27][N:26]2[CH2:1][C:3]2[CH:18]=[CH:17][C:6]([O:7][C:8]3[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[CH:10][N:9]=3)=[CH:5][CH:4]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

6

Reactant 5

HCID 111,2-DichloroethaneHCID 176Acetic AcidHCID 2618922-PhenylpyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 568514226-(4-Formylphenoxy)pyridine-3-carboxamide2×

Product 1

HCID 68745155(+/-)-6-[4-(2-Phenyl-pyrrolidin-1-ylmethyl)-phenoxy]-nicotinamide hydrochlorideYield 3.9%

Procedure

Combine 6-(4-formyl-phenoxy)-nicotinamide (compound of example 332, step 1) (0.150 g, 0.619 mmol), 2-phenyl-pyrrolidine (0.095 g, 0.64 mmol), sodium triacetoxyborohydride (0.194 g, 0.915 mmol), and acetic acid (0.051 mL, 0.891 mmol) in 1,2-dichloroethane (9.0 mL). After about 24 hours, purify the reaction mixture by ion exchange chromatography (SCX resin, methanol→2 M ammonia/methanol) and concentrate. Dissolve the residue in 1,4-dioxane and treated with 4 N hydrochloric acid in dioxane. Isolate the white precipitate by vacuum filtration. The solid became a yellowish syrup after approximately 3 min. on vacuum. Dissolve the residue in 1,4-dioxane and concentrate to provide 0.0100 g (3.9%) of the title compound as a white/yellow foam: high resolution mass spectrum (electrospray): m/z calc for C23H24N3O2 374.1869, found 374.1877; 1H NMR (methanol-d4): 8.63 (s, 1H), 8.35 (dd, 1H, J=1.5, 7.8 Hz), 7.64-7.44 (m, 7H), 7.24 (d, 2H, J=8.8 Hz), 7.11 (d, 1H, J=8.8 Hz), 4.69-4.60 (m, 1H), 4.28 (s, 2H), 3.75-3.66 (m, 1H), 3.58-3.47 (m, 1H), 2.71-2.60 (m, 1H), 2.45-2.22 (m, 3H).

Workup

  1. custompurify the reaction mixture by ion exchange chromatography (SCX resin, methanol→2 M ammonia/methanol)
  2. concentrationconcentrate
  3. dissolutionDissolve the residue in 1,4-dioxane
  4. additiontreated with 4 N hydrochloric acid in dioxane
  5. customIsolate the white precipitate
  6. filtrationby vacuum filtration
  7. customafter approximately 3 min.
  8. dissolutionDissolve the residue in 1,4-dioxane
  9. concentrationconcentrate

Sources & evidence

ORD record
ord-1a6845bd96a04a59891896411b343194
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Linked notes

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