Methyl iodide → HCID 67329422, compound

HRID 1846160Notes

Reaction equation

HRID 1846160 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([CH3:30])=[CH:11][C:12](N)=[N:13][C:14]=1[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][O:25][CH2:26][O:27][CH3:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N([O-])=O.[Na+].[OH-:35].[Na+].[CH3:37]I>O>[CH2:1]([O:8][C:9]1[C:14]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][O:25][CH2:26][O:27][CH3:28])=[N:13][C:12]([O:35][CH3:37])=[CH:11][C:10]=1[CH3:30])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 23668193Sodium NitriteHCID 67327786HCID 67327786, compound

Product 1

HCID 67329422HCID 67329422, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution at 0° C. containing 65 mg (0.16 mmol) of 5-(benzyloxy)-6-(10-(methoxymethoxy)decyl)-4-methylpyridin-2-amine in 2 mL of water-50% aqueous H3PO2 1:1 were added 17 mg (0.24 mmol) of sodium nitrite. The reaction mixture was stirred at 0° C. for 30 min and then at 23° C. for 16 h. The reaction mixture was neutralized (pH˜7) with aqueous NaOH and stirred for two hours. The reaction mixture was poured into 50 mL of water and extracted with two 40-mL portions of DCM. The combined organic layer was dried (MgSO4) and concentrated under diminished pressure. The residue was dissolved into 5 mL of anhydrous DCM. To the solution were added 100 μL (1.60 mmol) of methyl iodide followed by 66 mg (0.24 mmol) of Ag2CO3. The reaction mixture was stirred overnight at 23° C. and protected from light. The reaction mixture was filtered and the filtrate was concentrated under diminished pressure. The residue was purified by chromatography on a silica gel column (8×1 cm). Elution with 3:1 hexanes-ethyl acetate afforded the expected product as colorless oil: yield 18 mg (26%); silica gel TLC Rf 0.55 (4:1 hexanes-ethyl acetate) 1H NMR (CDCl3) δ 1.24-1.24 (m, 12H), 1.56 (quint, 2H, J=7.6 Hz), 1.70 (quint, 2H, J=7.6 Hz), 2.22 (s, 3H), 2.70 (dd, 2H, J=7.6, 7.6 Hz), 3.34 (s, 3H), 3.49 (t, 2H, J=6.8 Hz), 3.86 (s, 3H), 4.60 (s, 2H), 4.74 (s, 2H), 6.37 (s, 1H) and 7.33-7.44 (m, 5H); 13C NMR (CDCl3) δ 16.36, 26.19, 28.65, 29.42, 29.52, 29.54, 29.58, 29.65, 29.73, 31.77, 53.30, 55.05, 67.86, 75.31, 96.36, 108.75, 127.77, 128.07, 128.07, 128.53, 128.53, 137.29, 143.29, 146.62, 152.34 and 159.44; mass spectrum (APCI+), m/z 430.2965 (M+H) (C16H29N2O2 requires 430.2957).

Workup

  1. waitat 23° C. for 16 h
  2. stirringstirred for two hours
  3. extractionextracted with two 40-mL portions of DCM
  4. dry with materialThe combined organic layer was dried (MgSO4)
  5. concentrationconcentrated under diminished pressure
  6. dissolutionThe residue was dissolved into 5 mL of anhydrous DCM
  7. stirringThe reaction mixture was stirred overnight at 23° C.
  8. filtrationThe reaction mixture was filtered
  9. concentrationthe filtrate was concentrated under diminished pressure
  10. customThe residue was purified by chromatography on a silica gel column (8×1 cm)
  11. washElution with 3:1 hexanes-ethyl acetate

Sources & evidence

ORD record
ord-9d8e21634d2b449e9280099331e612cc
Source dataset
uspto-grants-2015_02
Patent number
US08952025B2

Reaction notes

Loading…