2,2'-Bipyridine → 4-{2-[5-(2-Aminomethyl-4-fluorophenoxy)-indazol-1-yl]-ethyl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 909233Notes

Reaction equation

HRID 909233 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]2[C:24]3[C:19](=[CH:20][C:21]([O:25][C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=4[C:33]#[N:34])=[CH:22][CH:23]=3)[CH:18]=[N:17]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1C1C=CC=CN=1.[BH4-].[Na+]>CCO>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([CH2:14][CH2:15][N:16]2[C:24]3[C:19](=[CH:20][C:21]([O:25][C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][C:27]=4[CH2:33][NH2:34])=[CH:22][CH:23]=3)[CH:18]=[N:17]2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 14742,2'-BipyridineHCID 4311764Sodium borohydrideHCID 674105684-{2-[5-(2-Cyano-4-fluorophenoxy)-indazol-1-yl]-ethyl}-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 674116794-{2-[5-(2-Aminomethyl-4-fluorophenoxy)-indazol-1-yl]-ethyl}-piperazine-1-carboxylic acid tert-butyl esterYield 86%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 4-{2-[5-(2-cyano-4-fluorophenoxy)-indazol-1-yl]-ethyl}-piperazine-1-carboxylic acid tert-butyl ester (0.160 g, 0.344 mmol), CoBr2 (0.008 g, 0.034 mmol), [2,2′]bipyridinyl (0.016 g, 0.010 mmol) in EtOH (6 mL) was added NaBH4 (0.039 g, 1.0 mmol). The mixture was stirred for 3 hours at room temperature. The reaction was quenched with MeOH (3 mL) and acetic acid (10 drops). The solution was concentrated under reduced pressure and diluted with ethyl acetate. The mixture was washed with aqueous NaHCO3, brine, dried over MgSO4, and concentrated under reduced pressure. The crude oil was chromatographed eluting with 1% triethylamine in ethyl acetate, MeOH/CH2Cl2/hexanes (1:15:15, 1% triethylamine), then MeOH/CH2Cl2/hexanes (1:10:10, 1% triethylamine). The pure product was obtained in 86% yield.

Workup

  1. customThe reaction was quenched with MeOH (3 mL) and acetic acid (10 drops)
  2. concentrationThe solution was concentrated under reduced pressure
  3. additiondiluted with ethyl acetate
  4. washThe mixture was washed with aqueous NaHCO3, brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude oil was chromatographed
  8. washeluting with 1% triethylamine in ethyl acetate, MeOH/CH2Cl2/hexanes (1:15:15, 1% triethylamine)
  9. customThe pure product was obtained in 86% yield

Sources & evidence

ORD record
ord-3cb983571ee645adb4bfc654d260daa0
Source dataset
uspto-grants-2011_09
Patent number
US08017641B2

Reaction notes

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