Methyl iodide → HCID 492673, compound

HRID 841543Notes

Reaction equation

HRID 841543 reaction equation
[F:1][C:2]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([NH:14][C:15](=[O:17])[CH3:16])[C:8]=2[N:7]=[C:6]1[C:18]1[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:19]=1[F:25].[CH3:31]I.[H-].[Na+]>C1COCC1>[F:1][C:2]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([N:14]([CH3:31])[C:15](=[O:17])[CH3:16])[C:8]=2[N:7]=[C:6]1[C:18]1[C:19]([F:25])=[CH:20][CH:21]=[CH:22][C:23]=1[F:24]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 492676HCID 492676, compound

Product 1

HCID 492673HCID 492673, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-acetamidobenzimidazole (Example 88) (2.44 g, 5.90 mmol) and methyl iodide (0.60 mL, 9.69 mmol) dissolved in THF (30 mL) was added excess NaH. After stirring overnight, the solution was concentrated to dryness, diluted with CH2Cl2, and washed with water, NaHSO4(10% soln) and NaCl (sat. aq). The combined washings were dried (Na2SO4), filtered, and concentrated. The crude product was purified by flash chromatography eluting with 2% methanol in CH2Cl2, yielding 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)-4-(N-methylacetamido)-benzimidazole (0.89 g, 2.08 mmol, 63% yield). M.p. 155-156° C. 1H NMR (200 MHz, CD2Cl2): δ7.55 (m, 1H, H4′), 7.48 (br d, J=7.4 Hz, 1H, H5), 7.31 (dd, J=7.4, 7.7 Hz, 1H, H6), 7.27 (m, 1H, H4″), 7.14 (dd, J=1.1, 7.7 Hz, 1H, H7), 7.09 (m, 2H, H3′,5′), 6.84 (m, 2H, H3″,5″), 5.38 (s, 2H, CH2), 3.34 (s, 3H, NCH3), 1.83 (s, 3H, NAc).

Workup

  1. concentrationthe solution was concentrated to dryness
  2. additiondiluted with CH2Cl2
  3. washwashed with water, NaHSO4(10% soln) and NaCl (sat. aq)
  4. dry with materialThe combined washings were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography
  8. washeluting with 2% methanol in CH2Cl2

Sources & evidence

ORD record
ord-96a7664b8cba4f8f9b6bb2a9662e8b78
Source dataset
uspto-grants-2002_04
Patent number
US06369235B1

Reaction notes

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