Hydroxylamine → HCID 178513254, 화합물

HRID 841549노트

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HRID 841549 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(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]

참가 물질

5

반응물 3

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

생성물 1

HCID 178513254HCID 178513254, 화합물수율 87.3%

시약·촉매·용매 1

HCID 702Ethanol용매

실험 절차

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): δ7.84 (dd, J=1.1, 7.7 Hz, 1H, H5), 7.57 (m, 1H, H4′), 7.54 (dd, J=1.1, 8.2 Hz, 11H, 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).

후처리

  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

출처 및 근거

ORD 기록
ord-c695c4d6d2f44380811948dd466e9f78
출처 데이터셋
uspto-grants-2002_04
특허 번호
US06369235B1

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