Diisopropylethylamine → 2-Methylsulfanyl-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazole-4-carboxylic acid [2-cyclohex-1-enyl-4-(2-morpholin-4-yl-ethyl)-phenyl]-amide

HRID 1190160Notes

Reaction equation

HRID 1190160 reaction equation
[K+].[CH3:2][S:3][C:4]1[N:8]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[C:7]([C:17]([O-:19])=O)=[CH:6][N:5]=1.[C:20]1([C:26]2[CH:31]=[C:30]([CH2:32][CH2:33][N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[CH:29]=[CH:28][C:27]=2[NH2:40])[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]=1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:20]1([C:26]2[CH:31]=[C:30]([CH2:32][CH2:33][N:34]3[CH2:35][CH2:36][O:37][CH2:38][CH2:39]3)[CH:29]=[CH:28][C:27]=2[NH:40][C:17]([C:7]2[N:8]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:14])([CH3:15])[CH3:16])[C:4]([S:3][CH3:2])=[N:5][CH:6]=2)=[O:19])[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 58994521HCID 58994521, compoundHCID 689480902-Methylsulfanyl-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazole-4-carboxylate potassium salt

Product 1

HCID 589944202-Methylsulfanyl-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazole-4-carboxylic acid [2-cyclohex-1-enyl-4-(2-morpholin-4-yl-ethyl)-phenyl]-amideYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 2-methylsulfanyl-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazole-4-carboxylate potassium salt (90 mg, 0.28 mmol)(as prepared in the previous step), 2-cyclohex-1-enyl-4-(2-morpholin-4-yl-ethyl)-phenylamine (81 mg, 0.28 mmol)(as prepared in Example 33, step (c)), PyBrOP (170 mg, 0.37 mmol), and DIEA (0.10 mL, 0.57 mmol) in 1.5 mL of DCM was stirred for 8 h at RT. The mixture was diluted with 20 mL of DCM and washed with NaHCO3 (2×30 mL) and brine (30 mL) and dried over Na2SO4. Flash chromatography of the residue on Si gel with 100% EtOAc gave the title compound as a white solid (107 mg, 70%). Mass spectrum (ESI, m/z): Calcd. for C29H44N4O3SSi, 557.3 (M+H). found 556.8.

Workup

  1. washwashed with NaHCO3 (2×30 mL) and brine (30 mL)
  2. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-b57fb693234c4eb2b6bcd571d8cbaae1
Source dataset
uspto-grants-2014_03
Patent number
US08674100B2

Reaction notes

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