Hydroxylamine → HCID 178513254, compound

HRID 2182101Notes

Reaction equation

HRID 2182101 reaction equation
[F:1][C:2]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:3]=1[CH2:4][N:5]1[C:9]2[CH:10]=[CH:11][CH:12]=[C:13]([C:14]#[N:15])[C:8]=2[N:7]=[C:6]1[C:16]1[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=1[F:23].C(N(CC)CC)C.[NH2:36][OH:37]>C(O)C>[OH:37][NH:36][C:14]([C:13]1[C:8]2[N:7]=[C:6]([C:16]3[C:17]([F:23])=[CH:18][CH:19]=[CH:20][C:21]=3[F:22])[N:5]([CH2:4][C:3]3[C:24]([F:28])=[CH:25][CH:26]=[CH:27][C:2]=3[F:1])[C:9]=2[CH:10]=[CH:11][CH:12]=1)=[NH:15]

Participants

5

Reactant 3

HCID 787HydroxylamineHCID 8471TriethylamineHCID 98647011-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)benzimidazole-4-carbonitrile

Product 1

HCID 178513254HCID 178513254, compoundYield 87.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)benzimidazole-4-carbonitrile (Example 105) (0.60 g, 1.57 mmol) dissolved in ethanol (15 mL) and triethylamine (0.5 mL) was added hydroxylamine (0.14 g, 130 M %). After 24 h at reflux, the reaction was concentrated. The residue was redissolved in CH2Cl2 and washed with NaHSO4(10% soln), 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 4% methanol/CH2Cl2 and recrystallization from methanol, yielding white crystals of N-hydroxy 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)benzimidazole-4-carboxamidine (0.57 g, 1.37 mmol, 87% yield). M.p. 214-216° C. 1H NMR (200 MHz, CD2Cl2): δ 7.84 (dd, J=1.1, 7.7 Hz, 1H, H5), 7.57 (m, 1H, H4′), 7.54 (dd, J=1.1, 8.2 Hz, 1H, H7), 7.30 (dd, J=7.7, 8.2 Hz, 1H, H6), 7.28 (m, 1H, H4″), 7.11 (m, 2H, H3′,5′), 6.83 (m, 2H, H3″,5″), 6.61 (br, 2H, NH2), 5.39 (s, 2H, CH2PhF2).

Workup

  1. temperatureAfter 24 h at reflux
  2. concentrationthe reaction was concentrated
  3. dissolutionThe residue was redissolved in CH2Cl2
  4. washwashed with NaHSO4(10% soln), 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 4% methanol/CH2Cl2 and recrystallization from methanol

Sources & evidence

ORD record
ord-769a2eac0204475089f50df4f5af9def
Source dataset
uspto-grants-2005_05
Patent number
US06894068B2

Reaction notes

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