Cesium carbonate → 1-(3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(1-methyl-1H-benzo[d]imidazol-6-yl)phenoxy)propan-2-ol

HRID 1399817ノート

反応式

HRID 1399817 の反応式
Br[C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[O:5][CH2:6][CH:7]([OH:19])[CH2:8][N:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10]1.[CH3:23][N:24]1[C:28]2[CH:29]=[C:30](B3OC(C)(C)C(C)(C)O3)[CH:31]=[CH:32][C:27]=2[N:26]=[CH:25]1.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1.O>[CH2:10]1[C:11]2[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:17][CH2:18][N:9]1[CH2:8][CH:7]([OH:19])[CH2:6][O:5][C:4]1[CH:20]=[CH:21][CH:22]=[C:2]([C:30]2[CH:31]=[CH:32][C:27]3[N:26]=[CH:25][N:24]([CH3:23])[C:28]=3[CH:29]=2)[CH:3]=1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 429098461-(3-bromophenoxy)-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-olHCID 594746911-Methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-benzo[D]imidazole

生成物 1

HCID 867292341-(3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(1-methyl-1H-benzo[d]imidazol-6-yl)phenoxy)propan-2-ol収率 26.4%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 218864351,4-Dioxane--water (1/1)溶媒

反応条件

温度
120 °C

実験手順

To a solution of 1-(3-bromophenoxy)-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol (200 mg, 0.55 mmol) in a mixed solution (Dioxane/H2O=4/1 mL) were added 1-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazole (214 mg, 0.83 mmol), Pd(dppf)Cl2 (40 mg, 0.06 mmol) and Cs2CO3 (360 mg, 1.10 mmol). The reaction mixture was heated at 120° C. under microwave condition for 40 min. The solvent was removed by concentration and the residue was dissolved in ethyl acetate, washed with water. The separated organic layer was concentrated and the crude product was purified by preparative HPLC separation to give the title compound (60 mg, yield 26%) MS (ESI+) e/z: 414.1 [M+1]+. 1H NMR (MeOD, 400 MHz), δ ppm: 9.45 (s, 1H), 8.21 (s, 1H), 8.00-7.93 (m, 2H), 7.50-7.24 (m, 7H), 7.10-7.07 (m, 1H), 4.76-4.70 (m, 1H), 4.62-4.49 (m, 2H), 4.24 (s, 3H), 4.22-4.19 (m, 2H), 3.98-3.94 (m, 1H), 3.60-3.51 (m, 3H), 3.41-3.21 (m, 2H).

後処理

  1. customThe solvent was removed by concentration
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washwashed with water
  4. concentrationThe separated organic layer was concentrated
  5. customthe crude product was purified by preparative HPLC separation

出典と根拠

ORDレコード
ord-bc9b85261d634b5ea755cee4fa6454c3
出典データセット
uspto-grants-2014_12
特許番号
US08906900B2

反応ノート

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