Ethyl Acetate → 1-(3,4-dihydro-1H-isoquinolin-2-yl)-3-[3-(1H-indazol-6-yl)phenoxy]propan-2-ol

HRID 1051449Notes

Reaction equation

Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][CH:3]=1.[CH2:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH2:13][N:12]1[CH2:21][CH:22]([OH:40])[CH2:23][O:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:26]=1.C([O-])([O-])=O.[K+].[K+].CC(=O)OCC>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]>[NH:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([C:27]3[CH:26]=[C:25]([CH:30]=[CH:29][CH:28]=3)[O:24][CH2:23][CH:22]([OH:40])[CH2:21][N:12]3[CH2:13][CH2:14][C:15]4[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=4)[CH2:11]3)[CH:10]=2)[CH:6]=[N:7]1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 6-bromo-1H-indazole (64.2 mg, 0.326 mmol) in dioxane (4 ml) and water (1 mL) was added 1-(3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)propan-2-ol (200 mg, 0.489 mmol), Pd(dppf)Cl2 (24 mg, 0.03257 mmol) and K2CO3 (135 mg, 0.98 mmol) at 16° C. The reaction mixture was stirred for 16 h at 100° C. TLC (PE: EA=1:1) showed that the reaction was completed. The mixture was concentrated to provide a crude product which was purified by HPLC separation to give the title compound (22.0 mg, 11.3%) as a white solid. 1HNMR (CD3OD, 400 MHz) δ: 8.49 (br, 1H), 8.07 (s, 1H), 7.85-7.83 (m, 1H), 7.76-7.71 (m, 1H), 7.44-7.10 (m, 8H), 7.03-6.98 (m, 1H), 4.50-4.42 (m, 1H), 4.30 (s, 2H), 4.15-4.13 (m, 2H), 3.49-3.40 (m, 2H), 3.36-3.31 (m, 2H), 3.19-3.10 (m, 2H). LCMS (m/z): 400.2 [M+H]+

Workup

concentrationThe mixture was concentrated
customto provide a crude product which
customwas purified by HPLC separation

Sources & evidence

ORD record: ord-cf7b9ae0cbb845f19ac7890b05b185be
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09388173B2

Reaction notes

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