6-(2-amino-5-bromopyridin-3-yl)-3,4-dihydroisoquinolin-1(2H)-one → 6'-amino-N-ethyl-N-methyl-5'-(1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)-[2,3'-bipyridine]-5-sulfonamide

HRID 2091560Notes

Reaction equation

HRID 2091560 reaction equation
[CH2:1]([N:3]([CH3:17])[S:4]([C:7]1[CH:8]=[N:9][C:10]([Sn](C)(C)C)=[CH:11][CH:12]=1)(=[O:6])=[O:5])[CH3:2].[NH2:18][C:19]1[C:24]([C:25]2[CH:26]=[C:27]3[C:32](=[CH:33][CH:34]=2)[C:31](=[O:35])[NH:30][CH2:29][CH2:28]3)=[CH:23][C:22](Br)=[CH:21][N:20]=1>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:18][C:19]1[N:20]=[CH:21][C:22]([C:10]2[CH:11]=[CH:12][C:7]([S:4]([N:3]([CH2:1][CH3:2])[CH3:17])(=[O:6])=[O:5])=[CH:8][N:9]=2)=[CH:23][C:24]=1[C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][CH:34]=1)[C:31](=[O:35])[NH:30][CH2:29][CH2:28]2

Participants

5

Reactant 2

HCID 682933526-(2-amino-5-bromopyridin-3-yl)-3,4-dihydroisoquinolin-1(2H)-oneHCID 70655349N-ethyl-N-methyl-6-(trimethylstannyl)pyridine-3-sulfonamide

Product 1

HCID 706547986'-amino-N-ethyl-N-methyl-5'-(1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)-[2,3'-bipyridine]-5-sulfonamideYield 51%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of N-ethyl-N-methyl-6-(trimethylstannyl)pyridine-3-sulfonamide (225 mg, 0.6 mmol) and 6-(2-amino-5-bromopyridin-3-yl)-3,4-dihydroisoquinolin-1(2H)-one (190 mg, 0.6 mmol) and Pd(PPh3)4 (34 mg, 0.03 mmol) in dioxane (3 mL) was degassed and heated to 90° C. At completion, the reaction was cooled to room temperature and concentrated. The residue was purified by flash chromatography over silica gel to provide 6′-amino-N-ethyl-N-methyl-5′-(1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)-[2,3′-bipyridine]-5-sulfonamide as a yellow solid (134 mg, 50% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.88 (dd, J=17.9, 2.1 Hz, 2H), 8.17-8.22 (m, 1H), 8.10-8.16 (m, 2H), 7.94 (d, J=7.8 Hz, 2H), 7.43-7.51 (m, 2H), 3.41 (s, 2H), 3.30 (s, 3H), 2.97 (t, J=6.4 Hz, 2H), 0.86 (t, J=7.3 Hz, 3H); MS (EI) m/z=438.5 [M+1]+.

Workup

  1. customwas degassed
  2. temperatureAt completion, the reaction was cooled to room temperature
  3. concentrationconcentrated
  4. customThe residue was purified by flash chromatography over silica gel

Sources & evidence

ORD record
ord-8b4a1cb971ea44468a05552512d118b0
Source dataset
uspto-grants-2013_05
Patent number
US08440652B2

Reaction notes

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