Potassium Carbonate → 2-(3,4-Dimethoxy-benzyl)-4-[8-(1-phenyl-ethyl)-3,8-diaza-bicyclo[3.2.1]oct-3-yl]-isoindole-1,3-dione

HRID 42324

반응식

HRID 42324 반응식
[CH2:1]([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH2:10][N:11]([C:16]1[CH:24]=[CH:23][CH:22]=[C:21]3[C:17]=1[C:18](=[O:37])[N:19]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[C:29]([O:35][CH3:36])[CH:28]=1)[C:20]3=[O:25])[CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH:39](C1C=CC=CC=1)C.C([O-])([O-])=O.[K+].[K+]>CCOC(C)=O.[Pd]>[CH3:36][O:35][C:29]1[CH:28]=[C:27]([CH:32]=[CH:31][C:30]=1[O:33][CH3:34])[CH2:26][N:19]1[C:18](=[O:37])[C:17]2[C:21](=[CH:22][CH:23]=[CH:24][C:16]=2[N:11]2[CH2:10][CH:9]3[N:8]([CH:1]([C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH3:39])[CH:13]([CH2:14][CH2:15]3)[CH2:12]2)[C:20]1=[O:25]

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 11454(1-Bromoethyl)benzeneHCID 236274934-(8-Benzyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione

생성물 1

HCID 582958642-(3,4-Dimethoxy-benzyl)-4-[8-(1-phenyl-ethyl)-3,8-diaza-bicyclo[3.2.1]oct-3-yl]-isoindole-1,3-dione수율 38.5%

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 8857Ethyl Acetate용매

반응 조건

온도
50 °C

실험 절차

Compound 7 (50 mg, 0.10 mmol) was hydrogenated (50 psi H2) with 10% Pd/C (5 mg) in EtOAc (1.0 mL) for 5 h. The mixture was filtered through Celite®, and concentrated in vacuo. The crude oil was dissolved in THF (0.4 mL). A portion of 1-bromoethylbenzene (0.03 mL, 0.22 mmol) and K2CO3 (36 mg, 0.26 mmol) were added. The mixture was heated to 50° C. for 4 h. The mixture was cooled to room temperature, filtered through Celite®, and concentrated in vacuo. The crude oil was purified on a Gilson HPLC with a reversed phase Kromasil column (10μ, 100 Å C18, column length 250×50 mm, gradient 90:10-0:100 H2O:MeCN) to give the 19.7 mg (38%) of the title Compound 32 as a yellow solid. 1H NMR (300 MHz, CDCl3) δ 7.71 (ovdd, J=7.6 Hz, 1 H), 7.49-7.60 (m, 6 H), 7.30 (d, J=8.2 Hz, 1 H), 6.94-7.00 (m, 1 H), 6.86-6.91 (m, 2 H), 4.73 (s, 2 H), 4.00-4.11 (m, 1 H), 3.81 (s, 3 H), 3.80 (s, 3 H), 3.43-3.60 (m, 4 H), 2.67-2.75 (m, 2 H), 2.43-2.51 (m, 2 H), 2.17-2.25 (m, 2 H), and 1.82 (d, J=6.7 Hz, 3 H); MS (ES+) 512.

후처리

  1. customfor 5 h
  2. filtrationThe mixture was filtered through Celite®
  3. concentrationconcentrated in vacuo
  4. dissolutionThe crude oil was dissolved in THF (0.4 mL)
  5. temperatureThe mixture was cooled to room temperature
  6. filtrationfiltered through Celite®
  7. concentrationconcentrated in vacuo
  8. customThe crude oil was purified on a Gilson HPLC with a reversed phase Kromasil column (10μ, 100 Å C18, column length 250×50 mm, gradient 90:10-0:100 H2O:MeCN)

출처 및 근거

ORD 기록
ord-925986818537439eb18a22eee1996541
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536174B2

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