Acetonitrile → 6-(2-amino-5-(4-(ethylsulfonyl)phenyl)pyridin-3-yl)-3,4-dihydroisoquinolin-1(2H)-one

HRID 2091556Notes

Reaction equation

Br[C:2]1[C:3]([NH2:19])=[N:4][CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH2:17][CH3:18])(=[O:16])=[O:15])=[CH:10][CH:9]=2)[CH:7]=1.[O:20]=[C:21]1[C:30]2[C:25](=[CH:26][C:27](B(O)O)=[CH:28][CH:29]=2)[CH2:24][CH2:23][NH:22]1.C([O-])([O-])=O.[Na+].[Na+].CC#N>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH2:19][C:3]1[C:2]([C:27]2[CH:26]=[C:25]3[C:30](=[CH:29][CH:28]=2)[C:21](=[O:20])[NH:22][CH2:23][CH2:24]3)=[CH:7][C:6]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH2:17][CH3:18])(=[O:16])=[O:15])=[CH:10][CH:9]=2)=[CH:5][N:4]=1

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of the 3-bromo-5-(4-(ethylsulfonyl)phenyl)pyridin-2-amine (100 mg, 0.29 mmol), 1-oxo-1,2,3,4-tetrahydroisoquinolin-6-ylboronic acid (75 mg, 0.29 mmol), PdCl2(PPh3)2 (7.0 mg, 0.01 mmol) and Na2CO3 in 3:1 MeCN:H2O was microwave heated at 150° C. for 3 min. At completion, the reaction mixture was filtered, then purified by preparatory HPLC to provide 6-(2-amino-5-(4-(ethylsulfonyl)phenyl)pyridin-3-yl)-3,4-dihydroisoquinolin-1(2H)-one as a pale yellow solid (48 mg, 41% yield) after reverse phase preparatory HPLC purification. 1H NMR (400 MHz, MeOD) δ ppm 8.37 (d, J=2.5 Hz, 1H), 8.06 (d, J=8.0 Hz, 1H), 7.94 (d, J=8.5 Hz, 2H), 7.89 (d, J=8.5 Hz, 2H), 7.81 (d, J=2.5 Hz, 1H), 7.53 (d, J=7.8 Hz, 1H), 7.49 (s, 1H), 3.56 (t, J=6.7 Hz, 2H), 3.19-3.27 (m, 2H), 3.07 (q, J=6.5 Hz, 2H), 1.25 (t, J=7.3 Hz, 3 H); MS (EI) m/z: 408 [M+H]+.

Workup

filtrationAt completion, the reaction mixture was filtered
custompurified by preparatory HPLC

Sources & evidence

ORD record: ord-95d6bf7f042446f1b66c94822008dcc1
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08440652B2

Reaction notes

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