Methyl 2-(2,6-difluorophenyl)-1-[(2,6-difluorophenyl)methyl]benzimidazole-4-carboxylate → 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)benzimidazole-4-carbonitrile

HRID 841548

反応式

HRID 841548 の反応式
[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]([C:14](OC)=O)[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].[Al]([NH2:34])(C)C>C1(C)C(C)=CC=CC=1>[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]([C:14]#[N:34])[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]

参加物

4

反応物 2

HCID 492679Methyl 2-(2,6-difluorophenyl)-1-[(2,6-difluorophenyl)methyl]benzimidazole-4-carboxylateHCID 16689643Aminodimethyl aluminium

生成物 1

HCID 98647011-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)benzimidazole-4-carbonitrile収率 61%

試薬・触媒・溶媒 1

HCID 7237O-Xylene溶媒

実験手順

To methyl 1-(2,6-difluorobenyl)-2-(2,6-difluorophenyl)benzimidazole-4-carboxylate (Example 102) (1.02 g, 2.46 mmol) suspended in xylene (60 mL) was added freshly prepared 1.0 M AlMe2NH2 (20 mL). After 3 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 2% methanol/CH2Cl2 and recrystallization from diethylether/hexane (3:1), yielding white crystals of 1-(2,6-Difluorobenzyl)-2-(2,6-difluorophenyl)- benzimidazole-4-carbonitrile (1.72 g, 4.51 mmol, 61% yield). M.p. 156-157° C.; 1H NMR (200 MHz, CD2Cl2): δ7.76 (dd, J=1.0, 8.6 Hz, 1H, H5), 7.63 (dd, J=1.0, 7.6 Hz, 1H, H7), 7.58 (m, 1H, H4′), 7.37 (dd, J=7.6, 8.6 Hz, 1H, H6), 7.28 (m, 1H, H4″), 7.11 (m, 2H, H3′,5′), 6.83 (m, 2H, H3″,5″), 5.40 (s, 2H, CH2PhF2).

後処理

  1. temperatureAfter 3 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 2% methanol/CH2Cl2 and recrystallization from diethylether/hexane (3:1)

出典と根拠

ORDレコード
ord-92a8004ae7e6413f9134a4d6524ad6c0
出典データセット
uspto-grants-2002_04
特許番号
US06369235B1

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