Diisopropylethylamine → 4-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid (2-cyclohex-1-enyl-pyridin-3-yl)-amide

HRID 1711276Notes

Reaction equation

HRID 1711276 reaction equation
[C:1]1([C:7]2[C:12]([NH2:13])=[CH:11][CH:10]=[CH:9][N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[K+].[C:39]([C:41]1[N:42]=[C:43]([C:54]([O-])=[O:55])[N:44]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:53])([CH3:52])[CH3:51])[CH:45]=1)#[N:40].CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]1([C:7]2[C:12]([NH:13][C:54]([C:43]3[N:44]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:53])([CH3:52])[CH3:51])[CH:45]=[C:41]([C:39]#[N:40])[N:42]=3)=[O:55])=[CH:11][CH:10]=[CH:9][N:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 587548302-Cyclohex-1-enyl-pyridin-3-ylamineHCID 67188357potassium 4-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxylate

Product 1

HCID 587548614-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid (2-cyclohex-1-enyl-pyridin-3-yl)-amideYield 69.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 365 mg (2.10 mmol) of 2-cyclohex-1-enyl-pyridin-3-ylamine (as prepared in the previous step) in CH2Cl2 (10 mL) was treated with 1.46 g (3.14 mmol) of PyBroP, 704 mg (2.30 mmol) of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate potassium salt (as prepared in Example 11, step (d)), and 1.09 mL (6.28 mmol) of DIEA at RT for 3 h. The mixture was diluted with CH2Cl2 (20 mL) and washed with saturated aqueous NaHCO3 (1×15 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 1% MeOH—CH2Cl2 afforded 615 mg (69%) of the title compound as a white solid: 1H-NMR (CDCl3; 400 MHz): δ 9.86 (br s, 1H), 8.69 (dd, 1H, J=8.0, 1.6 Hz), 8.37-8.34 (m, 1H), 7.78 (s, 1H), 7.22-7.17 (m, 1H), 6.05 (sept, 1H, J=1.6 Hz), 5.93 (s, 2H), 3.68-3.63 (m, 2H), 2.45-2.39 (m, 2H), 2.37-2.30 (m, 2H), 1.91-1.77 (m, 4H), 1.00-0.95 (m, 2H), 0.00 (s, 9H).

Workup

  1. washwashed with saturated aqueous NaHCO3 (1×15 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d9ec9da7aa8a4c2cb6c327dafaee8318
Source dataset
uspto-grants-2010_09
Patent number
US07790724B2

Reaction notes

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