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

반응식

HRID 841548 반응식
[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]

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 7237O-Xylene용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-92a8004ae7e6413f9134a4d6524ad6c0
출처 데이터셋
uspto-grants-2002_04
특허 번호
US06369235B1

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