Potassium Carbonate → 1-(3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(1-(4-methoxybenzyl)-1H-benzo[d]imidazol-6-yl)phenoxy)propan-2-ol

HRID 1051454Notes

Reaction equation

HRID 1051454 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[CH:8][N:7]([CH2:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)[C:6]=2[CH:19]=1.[CH2:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][CH2:22][N:21]1[CH2:30][CH:31]([OH:49])[CH2:32][O:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36](B2OC(C)(C)C(C)(C)O2)[CH:35]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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]>[CH2:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][CH2:22][N:21]1[CH2:30][CH:31]([OH:49])[CH2:32][O:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([C:2]2[CH:3]=[CH:4][C:5]3[N:9]=[CH:8][N:7]([CH2:10][C:11]4[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=4)[C:6]=3[CH:19]=2)[CH:35]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 867292361-(3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)propan-2-olHCID 867292426-bromo-1-(4-methoxybenzyl)-1H-benzo[d]imidazole

Product 1

HCID 867292431-(3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(1-(4-methoxybenzyl)-1H-benzo[d]imidazol-6-yl)phenoxy)propan-2-olYield 24.2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-bromo-1-(4-methoxybenzyl)-1H-benzo[d]imidazole (200 mg, 0.63 mmol), 1-(3,4-dihydroisoquinolin-2-(1H)-yl)-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)propan-2-ol (284 mg, 0.69 mmol), K2CO3 (261 mg, 1.89 mmol) and Pd(dppf)Cl2 (50 mg) in dioxane (8 mL) and H2O (2 mL) was stirred at 100° C. for 16 h. The catalyst was filtered and the filtrate concentrated. The residue was then purified by Prep-HPLC to give the title compound (79 mg, 24.2%). 1HNMR(CH3OD, 400 MHz) δ: 8.39 (br, 1H), 8.25 (s, 1H), 7.73-7.68 (m, 1H), 7.64-7.61 (m, 1H), 7.56-7.48 (m, 1H), 7.48-7.42 (m, 1H), 7.28-7.14 (m, 8H), 6.97-6.85 (m, 3H), 5.44 (s, 2H), 4.50-4.45 (m, 1H), 4.35 (s, 2H), 4.10-4.09 (m, 2H), 3.70 (s, 3H), 3.51-3.48 (m, 2H), 3.36-3.31 (m, 2H), 3.19-3.10 (m, 2H). LCMS (m/z): 520.2 [M+H]

Workup

  1. filtrationThe catalyst was filtered
  2. concentrationthe filtrate concentrated
  3. customThe residue was then purified by Prep-HPLC

Sources & evidence

ORD record
ord-ea69f9bfe69e498b889239b7dd6ae52a
Source dataset
uspto-grants-2016_07
Patent number
US09388173B2

Reaction notes

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