Diisopropylethylamine → 4-(4-{[4-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbonyl]-amino}-3-cyclohex-1-enyl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1043281Notes

Reaction equation

HRID 1043281 reaction equation
[K+].[C:2]([C:4]1[N:5]=[C:6]([C:17]([O-:19])=O)[N:7]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[CH:8]=1)#[N:3].CCN(C(C)C)C(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[C:53]([O:57][C:58]([N:60]1[CH2:65][CH2:64][CH:63]([C:66]2[CH:71]=[CH:70][C:69]([NH2:72])=[C:68]([C:73]3[CH2:78][CH2:77][CH2:76][CH2:75][CH:74]=3)[CH:67]=2)[CH2:62][CH2:61]1)=[O:59])([CH3:56])([CH3:55])[CH3:54]>C(Cl)Cl.CCOC(C)=O>[C:53]([O:57][C:58]([N:60]1[CH2:65][CH2:64][CH:63]([C:66]2[CH:71]=[CH:70][C:69]([NH:72][C:17]([C:6]3[N:7]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:14])([CH3:15])[CH3:16])[CH:8]=[C:4]([C:2]#[N:3])[N:5]=3)=[O:19])=[C:68]([C:73]3[CH2:78][CH2:77][CH2:76][CH2:75][CH:74]=3)[CH:67]=2)[CH2:62][CH2:61]1)=[O:59])([CH3:56])([CH3:54])[CH3:55]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 568348504-(4-Amino-3-cyclohex-1-enyl-phenyl)-piperidine-1-carboxylic acid tert-butyl esterHCID 67188357potassium 4-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxylate

Product 1

HCID 568348514-(4-{[4-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbonyl]-amino}-3-cyclohex-1-enyl-phenyl)-piperidine-1-carboxylic acid tert-butyl esterYield 85%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate potassium salt (3.34 g, 10.9 mmol) (as prepared in Example 3, step (d)) in 20 mL DCM was added DIEA (3.8 mL, 21.8 mmol) and PyBroP (5.6 g, 12.0 mmol), and the reaction stirred at 25° C. for 15 min. A solution of 4-(4-amino-3-cyclohex-1-enyl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (3.9 g, 10.9 mmol) (as prepared in Example 13, step (d)) in 10 mL DCM was added and the reaction stirred for 8 h at 25° C. The reaction was diluted EtOAc (60 mL) and washed with NaHCO3 (2×60 mL) and brine (100 mL) and the organic layer was dried over Na2SO4 and then concentrated. The title compound was purified by flash chromatography (silica gel, 2% EtOAc/DCM) to give 5.5 g (85%) of the title compound as a yellow oil. Mass spectrum (ESI, m/z): Calcd. for C33H47N5O4Si, 606.2 (M+H). found 606.2.

Workup

  1. stirringthe reaction stirred for 8 h at 25° C
  2. washwashed with NaHCO3 (2×60 mL) and brine (100 mL)
  3. dry with materialthe organic layer was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe title compound was purified by flash chromatography (silica gel, 2% EtOAc/DCM)

Sources & evidence

ORD record
ord-71074b89028a4216b4d5f5e0ba6a6a9e
Source dataset
uspto-grants-2013_10
Patent number
US08557847B2

Reaction notes

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