Potassium Carbonate → 1-[4-methoxy-7-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-1H-pyrrolo[2,3-c]pyridin-3-yl]-2-[5-(2-pyridyl)-3,4-dihydro-1H-isoquinolin-2-yl]ethane-1,2-dione

HRID 885050Notes

Reaction equation

HRID 885050 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([O:31][CH3:32])=[C:6]2[C:10]([C:11](=[O:30])[C:12]([N:14]3[CH2:23][CH2:22][C:21]4[C:16](=[CH:17][CH:18]=[CH:19][C:20]=4[C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=4)[CH2:15]3)=[O:13])=[CH:9][NH:8][C:7]=12.[F:33][C:34]([F:41])([F:40])[C:35]1[N:39]=[CH:38][NH:37][N:36]=1.CN[C@@H]1CCCC[C@@H]1NC.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.[Cu]I>[CH3:32][O:31][C:5]1[CH:4]=[N:3][C:2]([N:37]2[CH:38]=[N:39][C:35]([C:34]([F:41])([F:40])[F:33])=[N:36]2)=[C:7]2[NH:8][CH:9]=[C:10]([C:11](=[O:30])[C:12]([N:14]3[CH2:23][CH2:22][C:21]4[C:16](=[CH:17][CH:18]=[CH:19][C:20]=4[C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=4)[CH2:15]3)=[O:13])[C:6]=12

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 7020757rac-(1R,2S)-N1,N2-dimethylcyclohexane-1,2-diamineHCID 580260391-(7-bromo-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(5-(pyridin-2-yl)-3,4-dihydroisoquinolin-2(1H)-yl)ethane-1,2-dioneHCID 178506277HCID 178506277, compound

Product 1

HCID 445556011-[4-methoxy-7-[3-(trifluoromethyl)-1,2,4-triazol-1-yl]-1H-pyrrolo[2,3-c]pyridin-3-yl]-2-[5-(2-pyridyl)-3,4-dihydro-1H-isoquinolin-2-yl]ethane-1,2-dione

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1-(7-bromo-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(5-(pyridin-2-yl)-3,4-dihydroisoquinolin-2(1H)-yl)ethane-1,2-dione (100 mg, 0.204 mmol), 3-(trifluoromethyl)-1H-1,2,4-triazole (55.8 mg, 0.407 mmol), (1R,2S)—N1,N2-dimethylcyclohexane-1,2-diamine (5.79 mg, 0.041 mmol), copper (I) iodide (19.38 mg, 0.102 mmol) and potassium carbonate (84 mg, 0.611 mmol) in dioxane (1 mL) was heated at 100° C. for 4 hours. LCMS indicated that the desired product was generated. The reaction mixture was filtered and the clear solution was purified by prep. HPLC to give 1-(4-methoxy-7-(3-(trifluoromethyl)-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(5-(pyridin-2-yl)-3,4-dihydroisoquinolin-2(1H)-yl)ethane-1,2-dione as white solid (35 mg, 30%). LCMS: m/e 548.18 (M+H)+, 2.50 min (method 10). 1H NMR (500 MHz, MeOD) δ ppm 2.85-3.08 (m, 2H) 3.74-4.04 (m, 5H) 4.81-5.09 (m, 2H) 7.37-7.71 (m, 3H) 7.88-7.96 (m, 1H) 7.97-8.18 (m, 2H) 8.33-8.43 (m, 1H) 8.52-8.70 (m, 1H) 8.82-8.96 (m, 1H) 9.51 (s, 1H).

Sources & evidence

ORD record
ord-d42c9cb9bd21416391eff060e0512707
Source dataset
uspto-grants-2012_08
Patent number
US08242124B2

Reaction notes

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