Imidazole → HCID 86695094, compound

HRID 1503915Notes

Reaction equation

HRID 1503915 reaction equation
[C:1]([CH:3]([OH:33])[CH2:4][C@H:5]1[CH2:16][CH2:15][C:14]2[S:13][C:12]3[N:11]=[CH:10][N:9]=[C:8]([O:17][CH:18]4[CH2:23][CH2:22][CH:21]([N:24]([CH3:32])[C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:20][CH2:19]4)[C:7]=3[C:6]1=2)#[N:2].N1C=CN=C1.[C:39]([Si:43](Cl)([CH3:45])[CH3:44])([CH3:42])([CH3:41])[CH3:40]>CN(C=O)C>[Si:43]([O:33][CH:3]([C:1]#[N:2])[CH2:4][C@H:5]1[CH2:16][CH2:15][C:14]2[S:13][C:12]3[N:11]=[CH:10][N:9]=[C:8]([O:17][CH:18]4[CH2:19][CH2:20][CH:21]([N:24]([CH3:32])[C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:28])[CH3:29])[CH2:22][CH2:23]4)[C:7]=3[C:6]1=2)([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:45])[CH3:44]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 86695095HCID 86695095, compound

Product 1

HCID 86695094HCID 86695094, compoundYield 93.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

Reference: For the preparation of the starting material compound 48.1, please refer to the experimental procedure for the synthesis of compound I-57. Into a 50-mL round-bottom flask, a solution of tert-butyl N-(4-[[(3R)-3-(2-cyano-2-hydroxyethyl)-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2(6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate (1.9 g, 4.02 mmol, 1.00 equiv) in 10 mL of distilled DMF was added imidazole (544 mg, 8.00 mmol, 2.0 equiv) and tert-butyl(chloro)dimethylsilane (905 mg, 6.00 mmol, 1.49 equiv) at 0° C. under nitrogen. The resulting solution was stirred for 2 h at 20° C. After completion, the reaction was then quenched by the addition of 20 mL of water and extracted with 3×80 mL of ethyl acetate. The combined organic layers were washed with brine (three times), dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by column chromatography on silica gel with EtOAc/petroleum ether (1:20 to 1:5) to give 2.2 g (93%) of the desired tert-butyl N-(4-[[(3R)-3-[2-[(tert-butyldimethylsilyl)oxy]-2-cyanoethyl]-7-thia-9,11-diazatricyclo[6.4.0.0[2,6]]dodeca-1(8),2 (6),9,11-tetraen-12-yl]oxy]cyclohexyl)-N-methylcarbamate as a yellow oil. MS: m/z 587 (M+H)+.

Workup

  1. customplease refer to the experimental procedure for the synthesis of compound I-57
  2. customAfter completion, the reaction was then quenched by the addition of 20 mL of water
  3. extractionextracted with 3×80 mL of ethyl acetate
  4. washThe combined organic layers were washed with brine (three times)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by column chromatography on silica gel with EtOAc/petroleum ether (1:20 to 1:5)

Sources & evidence

ORD record
ord-967bd9de7f4b430282d38a03514a17eb
Source dataset
uspto-grants-2015_12
Patent number
US09212190B2

Reaction notes

Loading…