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

HRID 1399817Notes

Reaction equation

HRID 1399817 reaction equation
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

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-bc9b85261d634b5ea755cee4fa6454c3
Source dataset
uspto-grants-2014_12
Patent number
US08906900B2

Reaction notes

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