Potassium Carbonate → 1-(3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(1,3-dimethyl-1H-indol-6-yl)phenoxy)propan-2-ol

HRID 1399864Notes

Reaction equation

Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH3:12])=[CH:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.[CH2:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16][CH2:15][N:14]1[CH2:23][CH:24]([OH:42])[CH2:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=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]>[CH2:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16][CH2:15][N:14]1[CH2:23][CH:24]([OH:42])[CH2:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([C:2]2[CH:10]=[C:9]3[C:5]([C:6]([CH3:12])=[CH:7][N:8]3[CH3:11])=[CH:4][CH:3]=2)[CH:28]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 6-bromo-1,3-dimethyl-1H-indole (200 mg, 0.89 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 (401 mg, 0.98 mmol), K2CO3 (369 mg, 2.67 mmol) and Pd(dppf)Cl2 (50 mg) in dioxane (8 mL) and H2O (2 mL) was stirred at 100° C. for 16 h under N2. The catalyst was filtered and the filtrate was concentrated. The residue was purified by prep-HPLC to afford the title compound (38 mg, Yield 10%). 1H NMR (400 MHz, MeOD): δ 8.42 (s, 1H), 7.52-7.50 (m, 2H), 7.37-7.25 (m, 7H), 7.16-7.14 (m, 1H), 6.93-6.89 (m, 2H), 4.48-4.45 (m, 1H), 4.34 (s, 2H), 4.11-4.09 (m, 2H), 3.76 (s, 3H), 3.50-3.47 (m, 2H), 3.36-3.31 (m, 2H), 3.31-3.14 (m, 2H), 2.30 (s, 3H) ppm; ESI-MS (m/z): 427.3 [M+1]+.

Workup

filtrationThe catalyst was filtered
concentrationthe filtrate was concentrated
customThe residue was purified by prep-HPLC

Sources & evidence

ORD record: ord-428963c6bb8b48cb9d84bacf423e31a9
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08906900B2

Reaction notes

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