tert-Butyl piperazine-1-carboxylate → 4-{2-[5-(2-Cyano-4-fluorophenoxy)-indazol-1-yl]-ethyl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 1897514Notes

Reaction equation

HRID 1897514 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[N:16]([CH2:20][CH:21]=O)[N:15]=[CH:14]3)=[C:6]([CH:9]=1)[C:7]#[N:8].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[C:36]([O:40][C:41]([N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1)=[O:42])([CH3:39])([CH3:38])[CH3:37]>ClC(Cl)C>[C:36]([O:40][C:41]([N:43]1[CH2:48][CH2:47][N:46]([CH2:21][CH2:20][N:16]2[C:17]3[C:13](=[CH:12][C:11]([O:10][C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:9][C:6]=4[C:7]#[N:8])=[CH:19][CH:18]=3)[CH:14]=[N:15]2)[CH2:45][CH2:44]1)=[O:42])([CH3:39])([CH3:37])[CH3:38]

Participants

5

Reactant 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 2724942TriacetoxyborohydrideHCID 574187725-Fluoro-2-[1-(2-oxoethyl)-1H-indazol-5-yloxy]-benzonitrile

Product 1

HCID 674105684-{2-[5-(2-Cyano-4-fluorophenoxy)-indazol-1-yl]-ethyl}-piperazine-1-carboxylic acid tert-butyl esterYield 60%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 5-fluoro-2-[1-(2-oxo-ethyl)-1H-indazol-5-yloxy]-benzonitrile (0.307 g, 1.04 mmol) and triacetoxyborohydride (0.66 g, 3.1 mmol) in dichloroethane (10 mL) was added piperazine-1-carboxylic acid tert-butyl ester (0.65 g, 3.49 mmol). The mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched with MeOH (2 mL) and diluted with ethyl acetate (100 mL). The solution was washed with aqueous NaHCO3, brine, dried over MgSO4, and concentrated under reduced pressure. The residue was chromatographed eluting with ethyl acetate/hexanes (2:3, with 1% triethylamine) to afford 0.29 g of product (60% yield).

Workup

  1. customThe reaction mixture was quenched with MeOH (2 mL)
  2. additiondiluted with ethyl acetate (100 mL)
  3. washThe solution was washed with aqueous NaHCO3, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was chromatographed
  7. washeluting with ethyl acetate/hexanes (2:3, with 1% triethylamine)

Sources & evidence

ORD record
ord-88fab86bc22b4fb18d03e3f1dc46815c
Source dataset
uspto-grants-2013_08
Patent number
US08518983B2

Reaction notes

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