Methyl iodide → HCID 58366293, compound

HRID 877417Notes

Reaction equation

HRID 877417 reaction equation
[Si]([O:8][CH:9]([C:22]1[NH:23][C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=2)=[N:25][N:26]=1)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)(C(C)(C)C)(C)C.[H-].[Na+].CI.[N+](CCCC)(CCCC)(CCCC)[CH2:38]CCC.[F-]>CC#N.C1COCC1.CCOC(C)=O>[CH3:38][N:25]1[C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=2)=[N:23][C:22]([CH:9]([OH:8])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:26]1

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 2724141Tetrabutylammonium FluorideHCID 178455210HCID 178455210, compound

Product 1

HCID 58366293HCID 58366293, compoundYield 41%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A sample of 2-(5-(1-(tert-butyldimethylsilyloxy)-7-phenylheptyl)-4H-1,2,4-triazol-3-yl)-pyridine (S64, 6 mg, 0.01 mmol) was dissolved in MeCN (142 μL) and cooled to 0° C. NaH (60%, 0.4 mg, 0.01 mmol) was added as a solid. After 5 min, MeI (1 μL) was added. Upon completion of the reaction (1.5 h), the solvent was removed in vacuo. The residue was purified by preparative thin layer chromatography (SiO2, 50% EtOAc-hexanes) to afford two separate compounds, the N1 and N2 alkylated triazoles (4.5 mg, 68%) as colorless oils. The individual N1 alkylated TBS ether (6.6 mg, 0.014 mmol) was dissolved in THF (178 μl), treated with Bu4NF (1 M in THF, 18 μL) and stirred at room temperature for 16 h under Ar. The reaction mixture was diluted with EtOAc, washed with saturated aqueous NaCl and dried over Na2SO4. Evaporation in vacuo yielded the crude alcohol that was purified by preparative thin layer chromatography (SiO2, 50% EtOAc-hexanes) to afford the title compound (2.0 mg, 41%) as a colorless oil (N1 isomer determined by HMBC): 1H NMR (CDCl3, 600 MHz) δ 8.68 (d, 1H, J=4.7 Hz), 8.19 (d, 1H, J=7.9 Hz). 7.82 (dt, 1H, J=1.8, 7.8 Hz), 7.35 (ddd, 1H, J=1.0, 4.8, 7.5 Hz), 7.26 (m, 2H), 7.15 (m, 3H), 4.82 (br s, 1H), 4.33 (s, 3H), 2.59 (t, 2H, J=7.7 Hz), 1.97 (m, 1H), 1.88 (m, 1H), 1.61 (m, 2H), 1.50 (m, 2H), 1.40 (m, 4H); 13C NMR (CDCl3, 150 MHz) δ 164.9, 152.3, 149.0, 148.1, 143.0, 137.1, 128.5, 128.4, 125.7, 124.2, 124.1, 68.7, 38.9, 37.1, 36.1, 31.6, 29.5, 29.4, 25.3; HRMS-ESI-TOF m/z 351.2179 ([M+H]+, C21H26N4O requires 351.2179).

Workup

  1. customUpon completion of the reaction (1.5 h)
  2. customthe solvent was removed in vacuo
  3. customThe residue was purified by preparative thin layer chromatography (SiO2, 50% EtOAc-hexanes)
  4. customto afford two
  5. customseparate compounds
  6. washwashed with saturated aqueous NaCl
  7. dry with materialdried over Na2SO4
  8. customEvaporation in vacuo
  9. customyielded the crude alcohol that
  10. customwas purified by preparative thin layer chromatography (SiO2, 50% EtOAc-hexanes)

Sources & evidence

ORD record
ord-476742f237a54877a578335459617f33
Source dataset
uspto-grants-2015_03
Patent number
US08987312B2

Reaction notes

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