Diisopropylethylamine → 4-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [4-(4-cyano-1,1-dioxo-hexahydro-1lambda6-thiopyran-4-yl)-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide

HRID 1054292Notes

Reaction equation

HRID 1054292 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:16]#[N:17])[CH2:13][CH2:12][S:11](=[O:15])(=[O:14])[CH2:10][CH2:9]2)=[CH:4][C:3]=1[C:18]1[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[CH2:20][CH:19]=1.[K+].[C:27]([C:29]1[N:30]=[C:31]([C:42]([O-])=[O:43])[N:32]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[CH:33]=1)#[N:28].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:16]([C:8]1([C:5]2[CH:6]=[CH:7][C:2]([NH:1][C:42]([C:31]3[N:32]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[CH:33]=[C:29]([C:27]#[N:28])[N:30]=3)=[O:43])=[C:3]([C:18]3[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[CH2:20][CH:19]=3)[CH:4]=2)[CH2:13][CH2:12][S:11](=[O:15])(=[O:14])[CH2:10][CH2:9]1)#[N:17]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 589950684-[4-Amino-3-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-1,1-dioxo-hexahydro-1lambda6-thiopyran-4-carbonitrileHCID 67188357potassium 4-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxylate

Product 1

HCID 589950484-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [4-(4-cyano-1,1-dioxo-hexahydro-1lambda6-thiopyran-4-yl)-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amideYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 4-[4-amino-3-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-1,1-dioxo-hexahydro-1λ6-thiopyran-4-carbonitrile (119 mg, 0.332 mmol, as prepared in the previous step) and 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylate potassium salt (123 mg, 0.398 mmol, as prepared in Example 1, step (d)) in CH2Cl2 (10 mL) was treated with PyBroP (217 mg, 0.465 mmol) and DIEA (231 μL, 1.33 mmol) at room temperature for 45 min. The mixture was diluted with CH2Cl2 (30 mL) and washed with satd aq NaHCO3 (1×30 mL). The aqueous layer was extracted with CH2Cl2 (1×30 mL), and the combined organic layers were dried over MgSO4 and concentrated in vacuo. Silica gel chromatography of the residue on a 20-g Isolute SPE column (FlashMaster system) with 10-25% EtOAc-hexane afforded the title compound (193 mg, 95%) as an off-white solid. Mass spectrum (ESI, m/z): Calcd. for C31H41N5O4SSi, 608.3 (M+H). found 608.3.

Workup

  1. washwashed with satd aq NaHCO3 (1×30 mL)
  2. extractionThe aqueous layer was extracted with CH2Cl2 (1×30 mL)
  3. dry with materialthe combined organic layers were dried over MgSO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d762aef70d0d4688a10130449fa34114
Source dataset
uspto-grants-2016_07
Patent number
US09394289B2

Reaction notes

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