Diisopropylethylamine → 4-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(2-methylsulfamoyl-ethyl)-phenyl]-amide

HRID 1508085Notes

Reaction equation

HRID 1508085 reaction equation
[CH3:1][NH:2][S:3]([CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][C:11]([NH2:14])=[C:10]([C:15]2[CH2:20][CH2:19][C:18]([CH3:22])([CH3:21])[CH2:17][CH:16]=2)[CH:9]=1)(=[O:5])=[O:4].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>[CH3:21][C:18]1([CH3:22])[CH2:19][CH2:20][C:15]([C:10]2[CH:9]=[C:8]([CH2:7][CH2:6][S:3](=[O:4])(=[O:5])[NH:2][CH3:1])[CH:13]=[CH:12][C:11]=2[NH:14][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])=[CH:16][CH2:17]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 589943732-[4-Amino-3-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-ethanesulfonic acid methylamideHCID 67188357potassium 4-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxylate

Product 1

HCID 589943914-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(2-methylsulfamoyl-ethyl)-phenyl]-amideYield 83.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 65.0 mg (0.202 mmol) of 2-[4-amino-3-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-ethanesulfonic acid methylamide (as prepared in the previous step) in CH2Cl2 (5 mL) was treated with 141 mg (0.303 mmol) of PyBroP, 67.7 mg (0.222 mmol) of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate potassium salt (as prepared in Example 1, step (d)), and 105 μL (0.605 mmol) of DIEA at RT for 2 h. The mixture was diluted with CH2Cl2 (10 mL) and washed with saturated aqueous NaHCO3 (1×10 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 50% EtOAc-hexane afforded 96.0 mg (83%) of the title compound as a white solid: Mass spectrum (ESI, m/z): Calcd. for C28H41N5O4SSi, 572.3 (M+H). found 572.0.

Workup

  1. washwashed with saturated aqueous NaHCO3 (1×10 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-98e15fb6f8ec48e4b5fca724996e0699
Source dataset
uspto-grants-2015_12
Patent number
US09221797B2

Reaction notes

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