Trimethylsilyl isocyanate → HCID 58303674, compound

HRID 876412Notes

Reaction equation

HRID 876412 reaction equation
[N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([O:20][CH:21]4[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]4)[CH:14]=[CH:15][CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.CCN(C(C)C)C(C)C.[Si]([N:40]=[C:41]=[O:42])(C)(C)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([O:20][CH:21]4[CH2:26][CH2:25][N:24]([C:41]([NH2:40])=[O:42])[CH2:23][CH2:22]4)[CH:14]=[CH:15][CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12

Participants

6

Reactant 3

HCID 70696Trimethylsilyl isocyanateHCID 81531DiisopropylethylamineHCID 58303695HCID 58303695, compound

Product 1

HCID 58303674HCID 58303674, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-8-(piperidin-4-yloxy)quinoline (prepared as described in Example 9, 46 mg, 0.133 mmol) in CH2Cl2 (5 mL) were added DIEA (116 μL, 0.67 mmol), DMAP (2 mg, 0.01 mmol), and TMS-isocyanate (104 μL, 0.67 mmol). The reaction mixture was stirred at ambient temperature for 16 hours then partitioned between saturated NaHCO3 and CH2Cl2. The aqueous layer was extracted with CH2Cl2 and the combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography with gradient elution (CH2Cl2 to 1% MeOH/CH2Cl2 to 3% MeOH/CH2Cl2) to afford desired product (33 mg, 64%) as a colorless glass. MS ESI (+) m/z 411.2 (M+Na+) detected.

Workup

  1. customthen partitioned between saturated NaHCO3 and CH2Cl2
  2. extractionThe aqueous layer was extracted with CH2Cl2
  3. washthe combined organic phases were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography with gradient elution (CH2Cl2 to 1% MeOH/CH2Cl2 to 3% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-b66a84bac29145198ff5f581f1be4dd1
Source dataset
uspto-grants-2015_03
Patent number
US08987251B2

Reaction notes

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