Methanol → HCID 178481494, compound

HRID 447996Notes

Reaction equation

HRID 447996 reaction equation
[C:1]1([C:7]2[CH:12]=[C:11]([CH:13]3[CH2:18][C:17](=[O:19])[N:16]([CH3:20])[C:15](=[O:21])[CH2:14]3)[CH:10]=[CH:9][C:8]=2[NH:22][C:23]([C:25]2[N:26](COCC[Si](C)(C)C)[CH:27]=[C:28]([C:30]#[N:31])[N:29]=2)=[O:24])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.CO.C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:1]1([C:7]2[CH:12]=[C:11]([CH:13]3[CH2:18][C:17](=[O:19])[N:16]([CH3:20])[C:15](=[O:21])[CH2:14]3)[CH:10]=[CH:9][C:8]=2[NH:22][C:23]([C:25]2[NH:26][CH:27]=[C:28]([C:30]#[N:31])[N:29]=2)=[O:24])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1

Participants

5

Reactant 3

HCID 887Methanol2×HCID 6422Trifluoroacetic acidHCID 597712494-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [2-cyclohex-1-enyl-4-(1-methyl-2,6-dioxo-piperidin-4-yl)-phenyl]-amide

Product 1

HCID 178481494HCID 178481494, compoundYield 8.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 130 mg (0.237 mmol) of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid[2-cyclohex-1-enyl-4-(1-methyl-2,6-dioxo-piperidin-4-yl)-phenyl]-amide (as prepared in the previous step) in CH2Cl2 (10 mL) was treated with MeOH (200 μL) and TFA (3 mL) at RT for 1.25 h. MeOH (30 mL) was added, the mixture was concentrated to half volume, MeOH (20 mL) was added, and the solvents were removed completely in vacuo at <35° C. Silica gel chromatography of the residue on a 50-g Varian MegaBond Elut SPE column with 25-50% EtOAc-hexane and by RP-HPLC (C18) with 10-80% CH3CN in 0.1% TFA/H2O over 30 min afforded 8.0 mg (8%) of the title compound as a white solid: 1H-NMR (CD3OD; 400 MHz): δ 8.19 (d, 1H, J=8.4 Hz), 8.03 (s, 1H), 7.24 (dd, 1H, J=8.4, 2.4 Hz), 7.16 (d, 1H, J=2.4 Hz), 5.87-5.82 (m, 1H), 3.47-3.37 (m, 1H), 3.16 (s, 3H), 2.96-2.91 (m, 4H), 2.33-2.25 (m, 4H), 1.92-1.77 (m, 4H). Mass spectrum (ESI, m/z): Calcd. for C23H23N5O3, 418.2 (M+H), found 418.1.

Workup

  1. concentrationthe mixture was concentrated to half volume, MeOH (20 mL)
  2. additionwas added
  3. customthe solvents were removed completely in vacuo at <35° C

Sources & evidence

ORD record
ord-ccfd1d2575e449bda44270a138c6a95f
Source dataset
uspto-grants-2013_07
Patent number
US08481564B2

Reaction notes

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