Hydrochloric Acid → HCID 492677, compound

HRID 841544Notes

Reaction equation

HRID 841544 reaction equation
[F:1][C:2]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([N:14](C)[C:15](=O)C)[C:8]=2[N:7]=[C:6]1[C:19]1[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=1[F:26].Cl>O>[F:1][C:2]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([NH:14][CH3:15])[C:8]=2[N:7]=[C:6]1[C:19]1[C:20]([F:26])=[CH:21][CH:22]=[CH:23][C:24]=1[F:25]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 492673HCID 492673, compound

Product 1

HCID 492677HCID 492677, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-(N-methylacetamido)-benzimidazole (Example 96) (0.50 g, 1.17 mmol) suspended in water (9.0 mL) was added HCl (1.0 mL). After 3 h at reflux, the solution was concentrated to dryness, diluted with ethylacetate, and washed with NaHCO3 (sat. aq) 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-methylamino)-benzimidazole (0.35 g, 78% yield). M.p. 194-195° C. 1H NMR (200 MHz, CD2Cl2): δ7.52 (m, 1H, H4′), 7.23 (m, 1H, H4″), 7.13 (dd, J=8.3, 8.0 Hz, 1H, H6), 7.07 (m, 2H, H3′,5′), 6.80 (m, 2H, H3″,5″), 6.76 (d, J=8.3 Hz, 1H, H5), 6.36 (d, J=8.0 Hz, 1H, H7), 5.29 (s, 2H, CH2PhF2), 2.96 (s, 3H, NCH3).

Workup

  1. temperatureAfter 3 h at reflux
  2. concentrationthe solution was concentrated to dryness
  3. additiondiluted with ethylacetate
  4. washwashed with NaHCO3 (sat. aq) and NaCl (sat. aq)
  5. dry with materialThe combined washings were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography
  9. washeluting with 2% methanol in CH2Cl2

Sources & evidence

ORD record
ord-88d07d5f107949299a687e196c51e832
Source dataset
uspto-grants-2002_04
Patent number
US06369235B1

Reaction notes

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