Acetone → [1-(3,5-Dichloro-benzyl)-1H-imidazol-2-ylmethyl]-(3-fluoro-benzyl)-isopropyl-amine

HRID 2101490Notes

Reaction equation

HRID 2101490 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:21]=[C:22]([Cl:24])[CH:23]=1)[CH2:5][N:6]1[CH:10]=[CH:9][N:8]=[C:7]1[CH2:11][NH:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1.[CH3:25][C:26]([CH3:28])=O.[BH3-]C#N.[Na+].O>CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:21]=[C:22]([Cl:24])[CH:23]=1)[CH2:5][N:6]1[CH:10]=[CH:9][N:8]=[C:7]1[CH2:11][N:12]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1)[CH:26]([CH3:28])[CH3:25]

Participants

6

Reactant 4

HCID 180AcetoneHCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 11951591HCID 11951591, compound

Product 1

HCID 11952310[1-(3,5-Dichloro-benzyl)-1H-imidazol-2-ylmethyl]-(3-fluoro-benzyl)-isopropyl-amineYield 26%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of [1-(3,5-dichloro-benzyl)-1H-imidazol-2-ylmethyl]-(3-fluoro-benzyl)-amine, (200 mg, 0.55 mmol), acetone (81 uL, 1.10 mmol) and 3A molecular sieves (300 mg) in MeOH (3 mL) was stirred at ambient temperature under N2. After 5 h, NaBH3CN was added and the mixture stirred for an additional 2 h. Water (2 mL) was added and the reaction mixture concentrated in vacuo. The residue was taken up in 1N NaOH (20 mL) and extracted with CH2Cl2 (3×30 mL). The combined extracts were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by chromatography (silica gel, 100% EtOAc) and the isolated product converted to the di-hydrochloride salt by treatment with excess anhydrous HCl in methanol solution. The volatiles were removed in vacuo to afford the desired product 6a (58 mg, 26%) as an off-white solid: ESI MS m/z 406 [C21H22Cl2FN3+H]+.

Workup

  1. stirringthe mixture stirred for an additional 2 h
  2. concentrationthe reaction mixture concentrated in vacuo
  3. extractionextracted with CH2Cl2 (3×30 mL)
  4. dry with materialThe combined extracts were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by chromatography (silica gel, 100% EtOAc)
  7. customThe volatiles were removed in vacuo

Sources & evidence

ORD record
ord-bca050e6ad224eed817f9827ec960fec
Source dataset
uspto-grants-2009_08
Patent number
US07572921B2

Reaction notes

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