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

HRID 1711272Notes

Reaction equation

HRID 1711272 reaction equation
[CH3:1][C:2]1([CH3:15])[CH2:7][CH2:6][C:5]([C:8]2[C:13]([NH2:14])=[CH:12][CH:11]=[CH:10][N:9]=2)=[CH:4][CH2:3]1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[K+].[C:41]([C:43]1[N:44]=[C:45]([C:56]([O-])=[O:57])[N:46]([CH2:48][O:49][CH2:50][CH2:51][Si:52]([CH3:55])([CH3:54])[CH3:53])[CH:47]=1)#[N:42].CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:1][C:2]1([CH3:15])[CH2:7][CH2:6][C:5]([C:8]2[C:13]([NH:14][C:56]([C:45]3[N:46]([CH2:48][O:49][CH2:50][CH2:51][Si:52]([CH3:55])([CH3:54])[CH3:53])[CH:47]=[C:43]([C:41]#[N:42])[N:44]=3)=[O:57])=[CH:12][CH:11]=[CH:10][N:9]=2)=[CH:4][CH2:3]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 587548632-(4,4-Dimethyl-cyclohex-1-enyl)-pyridin-3-ylamineHCID 67188357potassium 4-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxylate

Product 1

HCID 587548574-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-pyridin-3-yl]-amideYield 53.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 80.0 mg (0.395 mmol) of 2-(4,4-dimethyl-cyclohex-1-enyl)-pyridin-3-ylamine (as prepared in the previous step) in CH2Cl2 (10 mL) was treated with 277 mg (0.593 mmol) of PyBroP, 133 mg (0.435 mmol) of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate potassium salt (as prepared in Example 11, step (d)), and 207 μL (1.19 mmol) of DIEA. The mixture was stirred at RT for 17 h, diluted with CH2Cl2 (20 mL) and washed with water (1×10 mL). The aqueous layer was extracted with CH2Cl2 (1×10 mL), and the combined organic layers were dried (MgSO4) and concentrated in vacuo. Silica gel chromatography of the residue on a 10-g Isolute SPE column with 25% EtOAc-hexane afforded 95 mg (53%) of the title compound as a white solid: 1H-NMR (CDCl3; 400 MHz): δ 9.92 (br s, 1H), 8.72 (dd, 1H, J=8.0, 1.6 Hz), 8.37 (dd, 1H, J=4.4, 1.6 Hz), 7.77 (s, 1H), 7.23-7.18 (m, 1H), 6.00-5.94 (m, 1H), 5.93 (s, 2H), 3.70-3.63 (m, 2H), 2.51-2.43 (m, 2H), 2.18-2.11 (m, 2H), 1.61 (t, 2H, J=6.4 Hz), 1.12 (s, 6H), 1.00-0.94 (m, 2H), 0.00 (s, 9H).

Workup

  1. washwashed with water (1×10 mL)
  2. extractionThe aqueous layer was extracted with CH2Cl2 (1×10 mL)
  3. dry with materialthe combined organic layers were dried (MgSO4)
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cc6de4fbb795438a90e71f01cd85112a
Source dataset
uspto-grants-2010_09
Patent number
US07790724B2

Reaction notes

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