Lithium Hexamethyldisilazide → HCID 57747371, compound

HRID 386624Notes

Reaction equation

HRID 386624 reaction equation
[Br:1][C:2]1[CH:33]=[C:32]([CH3:34])[C:5]([O:6][C:7]2[C:8]3[NH:31][CH:30]=[CH:29][C:9]=3[N:10]=[C:11]([N:13]([C:21]3[CH:26]=[CH:25][C:24]([C:27]#[N:28])=[CH:23][CH:22]=3)[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[N:12]=2)=[C:4]([CH3:35])[CH:3]=1.[Li+].[CH3:37][Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH3:35])[C:5]([O:6][C:7]2[C:8]3[N:31]([CH3:37])[CH:30]=[CH:29][C:9]=3[N:10]=[C:11]([N:13]([C:21]3[CH:26]=[CH:25][C:24]([C:27]#[N:28])=[CH:23][CH:22]=3)[C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[N:12]=2)=[C:32]([CH3:34])[CH:33]=1

Participants

4

Reactant 2

HCID 2733832Lithium HexamethyldisilazideHCID 57747399HCID 57747399, compound

Product 1

HCID 57747371HCID 57747371, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a cold mixture of tert-butyl 4-(4-bromo-2,6-dimethylphenoxy)-5H-pyrrolo[3,2-d]pyrimidin-2-yl(4-cyanophenyl)carbamate (0.81 g, 1.5 mmol) in THF (5 ml) at −78° C. was added a solution of LiHMDS (1M, 2 ml, 2 mmol). The mixture was warmed to 0° C. over 2 hours and then was cooled to −78° C. Idomethane (0.37 ml, 6 mmol) was added and the mixture was warmed to room temperature over 2 hours and then stirred at this temperature for an additional 2 hours. The mixture was washed with brine, extracted with ethyl acetate (×3). The organic layers were combined dried over MgSO4 and concentrated to dryness. The crude material was purified by chromatography on silica to obtain the title compound (0.782 g, 1.42 mmol, 95%). 1H NMR (CDCl3, 400 MHz) δ 1.32 (s, 9H), 2.07 (s, 6H), 4.18 (s, 3H), 6.65 (d, J=3.8 Hz, 1H), 7.15 (d, J=8.8 Hz, 2H), 7.21 (s, 2H), 7.37 (d, J=3.8 Hz, 1H), 7.49 (d, J=8.8, 2H).

Workup

  1. temperaturewas cooled to −78° C
  2. additionIdomethane (0.37 ml, 6 mmol) was added
  3. temperaturethe mixture was warmed to room temperature over 2 hours
  4. washThe mixture was washed with brine
  5. extractionextracted with ethyl acetate (×3)
  6. dry with materialThe organic layers were combined dried over MgSO4
  7. concentrationconcentrated to dryness
  8. customThe crude material was purified by chromatography on silica

Sources & evidence

ORD record
ord-8f02c6e9664c4a229a53b64e6964bd84
Source dataset
uspto-grants-2013_02
Patent number
US08372852B2

Reaction notes

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