Hydrochloric Acid → HCID 492677, compound

HRID 2182086Notes

Reaction equation

HRID 2182086 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 (4005) (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, 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 (4006) (0.35 g, 78% yield):. M.p. 194-195° C. 1H-NMR (200 MHz, CD2Cl2) δ 7.52 (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-07ad0a481a3e48a08d3f5fa99387a895
Source dataset
uspto-grants-2005_05
Patent number
US06894068B2

Reaction notes

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