Diisopropylethylamine → 4-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [2-cyclohex-1-enyl-4-(1-methyl-2,6-dioxo-piperidin-4-yl)-phenyl]-amide

HRID 2219638Notes

Reaction equation

HRID 2219638 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][C:12](=[O:14])[N:11]([CH3:15])[C:10](=[O:16])[CH2:9]2)=[CH:4][C:3]=1[C:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH:18]=1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[K+].[C:48]([C:50]1[N:51]=[C:52]([C:63]([O-])=[O:64])[N:53]([CH2:55][O:56][CH2:57][CH2:58][Si:59]([CH3:62])([CH3:61])[CH3:60])[CH:54]=1)#[N:49].CCN(C(C)C)C(C)C>C(Cl)Cl>[C:17]1([C:3]2[CH:4]=[C:5]([CH:8]3[CH2:9][C:10](=[O:16])[N:11]([CH3:15])[C:12](=[O:14])[CH2:13]3)[CH:6]=[CH:7][C:2]=2[NH:1][C:63]([C:52]2[N:53]([CH2:55][O:56][CH2:57][CH2:58][Si:59]([CH3:62])([CH3:61])[CH3:60])[CH:54]=[C:50]([C:48]#[N:49])[N:51]=2)=[O:64])[CH2:22][CH2:21][CH2:20][CH2:19][CH:18]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 597712664-(4-Amino-3-cyclohex-1-enyl-phenyl)-1-methyl-piperidine-2,6-dioneHCID 67188357potassium 4-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxylate

Product 1

HCID 597712494-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [2-cyclohex-1-enyl-4-(1-methyl-2,6-dioxo-piperidin-4-yl)-phenyl]-amideYield 27%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 266 mg (0.891 mmol) of 4-(4-amino-3-cyclohex-1-enyl-phenyl)-1-methyl-piperidine-2,6-dione (as prepared in the previous step) in CH2Cl2 (10 mL) was treated with 623 mg (1.34 mmol) of PyBroP, 300 mg (0.981 mmol) of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate potassium salt (as prepared in Example 1, step (d)), and 466 μL (2.67 mmol) of DIEA at RT for 16 h. The mixture was diluted with CH2Cl2 (30 mL) and washed with saturated aqueous NaHCO3 (1×30 mL). The organic layer was dried (MgSO4) and concentrated in vacuo. Silica gel chromatography of the residue on a 50-g Varian MegaBond Elut SPE column with 25% EtOAc-hexane afforded 130 mg (27%) of the title compound as an off-white solid: Mass spectrum (ESI, m/z): Calcd. for C29H37N5O4Si, 548.3 (M+H). found 547.9.

Workup

  1. washwashed with saturated aqueous NaHCO3 (1×30 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ccbebfb00ec748a1b2bd36aeceba465a
Source dataset
uspto-grants-2008_08
Patent number
US07414050B2

Reaction notes

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