Methyl iodide → HCID 86689835, compound

HRID 2409022Notes

Reaction equation

HRID 2409022 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[N:15]=[C:14]2[CH:16]=[CH:17][N:18]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:13]2=[CH:12][CH:11]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].IC.[CH3:28][Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[C:1]([O:5][C:6]([N:8]([CH2:9][C:10]1[N:15]=[C:14]2[CH:16]=[CH:17][N:18]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[C:13]2=[CH:12][CH:11]=1)[CH3:28])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 86689836HCID 86689836, compound

Product 1

HCID 86689835HCID 86689835, compoundYield 37.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of tert-butyl 5-[(tert-butoxycarbonylamino)methyl]-pyrrolo-[3,2-b]pyridine-1-carboxylate (360.0 mg, 1.036 mmol) and iodomethane (0.065 mL, 1.036 mmol) in anhydrous THF (6.3 mL) cooled to −40° C. was added dropwise lithium bis(trimethylsilyl)amide in THF (1.24 mL, 1.24 mmol, 1M). The reaction mixture was warmed to 0° C. and stirred at 0° C. for 1 h. The reaction was quenched with water and then diluted with EtOAc. The organic layer was washed with water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The crude material was purified by SiO2 chromatography eluting with a mixture of EtOAc containing 1% TEA and heptane to afford 130.0 mg (37.3%) of tert-butyl 5-((tert-butoxycarbonyl(methyl)amino)methyl)-1H-pyrrolo[3,2-b]pyridine-1-carboxylate as a foam: 1H NMR (400 MHz, CDCl3) δ 8.33 (d, J=7.6 Hz, 1H), 7.82 (d, J=3.5 Hz, 1H), 7.27-7.10 (m, 1H), 6.73 (d, J=3.7 Hz, 1H), 4.64 (s, 2H), 3.02-2.82 (m, 3H), 1.68 (s, 9H), 1.56-1.41 (m, 9H); MS (ESI) m/z: 362.3 [M+1]+

Workup

  1. customThe reaction was quenched with water
  2. additiondiluted with EtOAc
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by SiO2 chromatography
  8. washeluting with a mixture of EtOAc containing 1% TEA and heptane

Sources & evidence

ORD record
ord-75c24ae0f4d544ca958862cca4a79539
Source dataset
uspto-grants-2014_08
Patent number
US08815877B2

Reaction notes

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