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 447995Notes

Reaction equation

HRID 447995 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 chromagography 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-79f1506cc6414890a19e1c7ea3e6554d
Source dataset
uspto-grants-2013_07
Patent number
US08481564B2

Reaction notes

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