Ethanol → HCID 178424466, compound

HRID 536974Notes

Reaction equation

HRID 536974 reaction equation
[C:1]([C:3]1([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]3[N:21](COCC[Si](C)(C)C)[CH:22]=[C:23]([C:25]#[N:26])[N:24]=3)=[O:19])=[C:13]([C:35]3[CH2:40][CH2:39][C:38]([CH3:42])([CH3:41])[CH2:37][CH:36]=3)[CH:12]=2)[CH2:8][CH2:7][S:6](=[O:10])(=[O:9])[CH2:5][CH2:4]1)#[N:2].C(O)(C(F)(F)F)=O.CCO>C(Cl)Cl>[C:1]([C:3]1([C:11]2[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]3[NH:21][CH:22]=[C:23]([C:25]#[N:26])[N:24]=3)=[O:19])=[C:13]([C:35]3[CH2:40][CH2:39][C:38]([CH3:42])([CH3:41])[CH2:37][CH:36]=3)[CH:12]=2)[CH2:4][CH2:5][S:6](=[O:9])(=[O:10])[CH2:7][CH2:8]1)#[N:2]

Participants

5

Reactant 3

HCID 702EthanolHCID 6422Trifluoroacetic acidHCID 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]-amide

Product 1

HCID 178424466HCID 178424466, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [4-(4-cyano-1,1-dioxo-hexahydro-1λ6-thiopyran-4-yl)-2-(4,4-dimethyl-cyclohex-1-enyl)-phenyl]-amide (193 mg, 0.318 mmol, as prepared in the previous step) in CH2Cl2 (10 mL) was treated with TFA (2 mL) and stirred at RT for 3 h. EtOH (5 mL) was added, and the mixture was concentrated to dryness. The residue was taken up in CH2Cl2 and carefully washed with satd aq NaHCO3 (1×). The aqueous layer was extracted with CH2Cl2 (1×), and the combined aqueous 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 25-50% EtOAc-hexane afforded the title compound (50.4 mg, 33%) as a white solid. 1H-NMR (CD3OD; 400 MHz): δ 8.39 (d, 1H, J=8.8 Hz), 8.01 (s, 1H), 7.53 (dd, 1H, J=8.8, 2.0 Hz), 7.42 (d, 1H, J=2.0 Hz), 5.85-5.80 (m, 1H), 3.59-3.46 (m, 2H), 2.81-2.69 (m, 2H), 2.62-2.52 (m, 2H), 2.39-2.32 (m, 2H), 2.17-2.10 (m, 2H), 1.68-1.58 (m, 4H), 1.13 (s, 6H). Mass spectrum (ESI, m/z): Calcd. for C25H27N5O3S, 478.2 (M+H). found 478.2.

Workup

  1. concentrationthe mixture was concentrated to dryness
  2. washcarefully washed with satd aq NaHCO3 (1×)
  3. extractionThe aqueous layer was extracted with CH2Cl2 (1×)
  4. dry with materialthe combined aqueous layers were dried over MgSO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cdba110d796c491587c19b2c098673ca
Source dataset
uspto-grants-2014_10
Patent number
US08859602B2

Reaction notes

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