Diisopropylethylamine → 4-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [2-cyclohex-1-enyl-4-(cis-3,5-dimethyl-piperazine-1-sulfonylmethyl)-phenyl]-amide

HRID 1190121Notes

Reaction equation

HRID 1190121 reaction equation
[C:1]1([C:7]2[CH:12]=[C:11]([CH2:13][S:14]([N:17]3[CH2:22][C@H:21]([CH3:23])[NH:20][C@H:19]([CH3:24])[CH2:18]3)(=[O:16])=[O:15])[CH:10]=[CH:9][C:8]=2[NH2:25])[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:51]([C:53]1[N:54]=[C:55]([C:66]([O-])=[O:67])[N:56]([CH2:58][O:59][CH2:60][CH2:61][Si:62]([CH3:65])([CH3:64])[CH3:63])[CH:57]=1)#[N:52].CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]1([C:7]2[CH:12]=[C:11]([CH2:13][S:14]([N:17]3[CH2:22][C@H:21]([CH3:23])[NH:20][C@H:19]([CH3:24])[CH2:18]3)(=[O:16])=[O:15])[CH:10]=[CH:9][C:8]=2[NH:25][C:66]([C:55]2[N:56]([CH2:58][O:59][CH2:60][CH2:61][Si:62]([CH3:65])([CH3:64])[CH3:63])[CH:57]=[C:53]([C:51]#[N:52])[N:54]=2)=[O:67])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 589943402-Cyclohex-1-enyl-4-(cis-3,5-dimethyl-piperazine-1-sulfonylmethyl)-phenylamineHCID 67188357potassium 4-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxylate

Product 1

HCID 589944124-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [2-cyclohex-1-enyl-4-(cis-3,5-dimethyl-piperazine-1-sulfonylmethyl)-phenyl]-amideYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 153 mg (0.422 mmol) of 2-cyclohex-1-enyl-4-(cis-3,5-dimethyl-piperazine-1-sulfonylmethyl)-phenylamine (as prepared in the previous step) in CH2Cl2 (10 mL) was treated with 295 mg (0.633 mmol) of PyBroP and 142 mg (0.464 mmol) of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate potassium salt (as prepared in Example 1, step (d)) to form a slurry, which was cooled to 0° C., treated with 184 μL (1.06 mmol) of DIEA, and warmed to RT for 6.5 h. The mixture was diluted with CH2Cl2 (15 mL) and washed with saturated aqueous NaHCO3 (1×15 mL) and brine (1×15 mL). The organic layer was dried (MgSO4) and concentrated in vacuo to afford 163 mg (63%) of the title compound as a white solid: Mass spectrum (ESI, m/z): Calcd. for C30H44N6O4SSi, 613.3 (M+H). found 612.9.

Workup

  1. customto form a slurry, which
  2. temperaturewarmed to RT for 6.5 h
  3. washwashed with saturated aqueous NaHCO3 (1×15 mL) and brine (1×15 mL)
  4. dry with materialThe organic layer was dried (MgSO4)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a13d1d9406dc467cb2488de2d2aaaeac
Source dataset
uspto-grants-2014_03
Patent number
US08674100B2

Reaction notes

Loading…