Hydrogen Peroxide → 2-(2,6-Difluorophenyl)-1-[(2,6-difluorophenyl)methyl]benzimidazole-4-carboxamide

HRID 2182102노트

반응식

HRID 2182102 반응식
[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([O-])([O-])=[O:30].[Na+].[Na+].OO>C(O)C>[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]([NH2:15])=[O:30])[C:8]=2[N:7]=[C:6]1[C:16]1[C:17]([F:23])=[CH:18][CH:19]=[CH:20][C:21]=1[F:22]

참가 물질

5

반응물 3

HCID 784Hydrogen PeroxideHCID 10340Sodium CarbonateHCID 98647011-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)benzimidazole-4-carbonitrile

생성물 1

HCID 4926802-(2,6-Difluorophenyl)-1-[(2,6-difluorophenyl)methyl]benzimidazole-4-carboxamide수율 72%

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

To 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)benzimidazole-4-carbonitrile (Example 105) (1.10 g, 2.88 mmol) dissolved in ethanol (100 mL) and 3 M Na2CO3 (10 mL) was added 30% hydrogen peroxide (10 mL). After stirring overnight at room temperature, the reaction was concentrated. The residue was then redissolved in EtOAc, 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 2% methanol/CH2Cl2 and recrystallization from methanol, yielding white crystals of 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)benzimidazole-4-carboxylic acid amide (0.83 g, 2.08 mmol, 72% yield). M.p. 260-261° C. 1H-NMR (200 MHz, CD2Cl2): δ 8.10 (dd, J=1.1, 7.7 Hz, 1H, H5), 7.71 (br d, J=8.1 Hz, 1H, H7), 7.59 (m, 1H, H4′), 7.43 (dd, J=7.7, 8.1 Hz, 1H, H6), 7.28 (m, 1H, H4″), 7.13 (m, 2H, H3′,5′), 6.84 (m, 2H, H3″,5″), 5.43 (s, 2H, CH2PhF2), 1.92 (s, 2H, NH2).

후처리

  1. concentrationthe reaction was concentrated
  2. dissolutionThe residue was then redissolved in EtOAc
  3. washwashed with NaHSO4(10% soln), NaHCO3 (sat. aq) 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/CH2Cl2 and recrystallization from methanol

출처 및 근거

ORD 기록
ord-69fbb2a635e044e780fc57d45001b0f2
출처 데이터셋
uspto-grants-2005_05
특허 번호
US06894068B2

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