Hydroquinone → 9-methyl-6-{2-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole

HRID 2176137노트

반응식

HRID 2176137 반응식
[Na].[CH3:2][C:3]1[CH:11]=[CH:10][C:9]2[NH:8][C:7]3[CH:12]4[CH2:18][CH2:17][N:15]([CH2:16][C:6]=3[C:5]=2[CH:4]=1)[CH2:14][CH2:13]4.[F:19][C:20]([F:30])([F:29])[C:21]1[CH:26]=[CH:25][C:24]([CH:27]=[CH2:28])=[CH:23][N:22]=1.C1(C=CC(O)=CC=1)O>CS(C)=O>[CH3:2][C:3]1[CH:11]=[CH:10][C:9]2[N:8]([CH2:28][CH2:27][C:24]3[CH:23]=[N:22][C:21]([C:20]([F:30])([F:19])[F:29])=[CH:26][CH:25]=3)[C:7]3[CH:12]4[CH2:13][CH2:14][N:15]([CH2:16][C:6]=3[C:5]=2[CH:4]=1)[CH2:17][CH2:18]4

참가 물질

6

반응물 4

HCID 785HydroquinoneHCID 5360545SodiumHCID 574168485-Ethenyl-2-(trifluoromethyl)pyridineHCID 67544841HCID 67544841, 화합물

생성물 1

HCID 453806669-methyl-6-{2-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매2회

반응 조건

온도
115 °C

실험 절차

Sodium dispersion in paraffin (30%, 46 mg, 0.60 mmol; Aldrich) was combined with 9-methyl-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole (100 mg, 0.442 mmol; Example 2B) in a 20 mL vial with stir bar and septum cap. Dimethyl sulfoxide (2.5 mL) was added, and the vial was evacuated and purged with nitrogen (10 cycles). The mixture was stirred at room temperature for 10 minutes, and a solution of the product of Example 143A (115 mg, 0.663 mmol) and hydroquinone (12 mg, 0.110 mmol) in dimethyl sulfoxide (0.5 mL) was added. The vial was evacuated and purged with nitrogen (5 cycles) and the mixture was stirred with heating at 115° C. for 39 hours. The dark brown mixture was cooled to room temperature, applied directly to a column of silica gel and eluted with chloroform, followed by CHCl3—CH3OH-14.8 M aqueous NH4OH (90:10:1). The product-containing fractions were combined and concentrated under vacuum, and the residue was purified by HPLC [Waters XBridge C18 5 μm OBD column, 30×100 mm, flow rate 40 mL/minute, 20-90% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide) over 20 minutes] to provide the title compound: 1H NMR (300 MHz, methanol-d4) δ 1.46-1.64 (m, 2H), 1.79-1.98 (m, 2H), 2.38 (s, 3H), 2.84-3.01 (m, 3H), 3.05-3.22 (m, 4H), 4.16 (s, 2H), 4.42 (t, J=6.27 Hz, 2H), 6.89 (dd, J=8.48, 1.02 Hz, 1H), 7.09 (d, J=7.80 Hz, 1H), 7.10 (d, J=0.68 Hz, 1H), 7.54 (dd, J=8.10, 1.70 Hz, 1H), 7.59 (d, J=8.10 Hz, 1H), 8.12 ppm (s, 1H); MS (ESI) m/z 400 (MH)+.

후처리

  1. customseptum cap
  2. customthe vial was evacuated
  3. custompurged with nitrogen (10 cycles)
  4. stirringThe mixture was stirred at room temperature for 10 minutes
  5. customThe vial was evacuated
  6. custompurged with nitrogen (5 cycles)
  7. stirringthe mixture was stirred
  8. temperatureThe dark brown mixture was cooled to room temperature
  9. washeluted with chloroform
  10. concentrationconcentrated under vacuum
  11. customthe residue was purified by HPLC [Waters XBridge C18 5 μm OBD column, 30×100 mm, flow rate 40 mL/minute, 20-90% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide) over 20 minutes]

출처 및 근거

ORD 기록
ord-eaf9018a155446039fb294dea3b614bd
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09063126B2

반응 노트

불러오는 중…