Potassium Carbonate → 5-[3-[3-(3,4-dihydro-1H-isoquinolin-2-yl)-2-hydroxypropoxy]phenyl]-1,3-dihydrobenzimidazol-2-one

HRID 1051470Notes

Reaction equation

Br[C:2]1[CH:11]=[CH:10][C:5]2[NH:6][C:7](=[O:9])[NH:8][C:4]=2[CH:3]=1.[CH2:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14][N:13]1[CH2:22][CH:23]([OH:41])[CH2:24][O:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=1.C([O-])([O-])=O.[K+].[K+]>O.O1CCOCC1.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]>[CH2:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][CH2:14][N:13]1[CH2:22][CH:23]([OH:41])[CH2:24][O:25][C:26]1[CH:27]=[C:28]([C:2]2[CH:11]=[CH:10][C:5]3[NH:6][C:7](=[O:9])[NH:8][C:4]=3[CH:3]=2)[CH:29]=[CH:30][CH:31]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 5-bromo-1H-benzo[d]imidazol-2(3H)-one (200 mg, 0.489 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 (100 mg), Pd(dppf)Cl2 (36 mg, 0.049 mmol), K2CO3 (202 mg, 1.47 mmol) in H2O-dioxane (1 mL/3 mL) was stirred and heated in am microwave reactor to 100° C. for 15 min. Once cooled, the solvent was removed by concentration and the crude product purified by HPLC separation to give the title compound (74 mg, 36.5%). 1HNMR (CH3OD, 400 MHz) δ: 7.49-7.10 (m, 10H), 6.98-6.92 (m, 1H), 4.76-4.42 (m, 3H), 4.20-4.09 (m, 2H), 3.98-3.89 (m, 1H), 3.62-3.48 (m, 3H), 3.36-3.14 (m, 2H). LCMS (m/z): 416.2 [M+H]+

Workup

temperatureOnce cooled
customthe solvent was removed by concentration
customthe crude product purified by HPLC separation

Sources & evidence

ORD record: ord-4129063689784e91ad8e8ad154f29648
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09388173B2

Reaction notes

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