Potassium Carbonate → HCID 44555792, compound

HRID 885051Notes

Reaction equation

HRID 885051 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]([C:37]1[N:41]=[CH:40][NH:39][N:38]=1)([F:36])[CH3:35].CN[C@@H]1CCCC[C@@H]1NC.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.[Cu]I>[F:33][C:34]([C:37]1[N:41]=[CH:40][N:39]([C:2]2[N:3]=[CH:4][C:5]([O:31][CH3:32])=[C:6]3[C:10]([C:11](=[O:30])[C:12]([N:14]4[CH2:23][CH2:22][C:21]5[C:16](=[CH:17][CH:18]=[CH:19][C:20]=5[C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=5)[CH2:15]4)=[O:13])=[CH:9][NH:8][C:7]=23)[N:38]=1)([F:36])[CH3:35]

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 178461133HCID 178461133, compound

Product 1

HCID 44555792HCID 44555792, compound

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-(1,1-difluoroethyl)-1H-1,2,4-triazole (54.2 mg, 0.407 mmol), (1R,2S)-N1,N2-dimethylcyclohexane-1,2-diamine (5.79 mg, 0.041 mmol), K2CO3 (84 mg, 0.611 mmol) and copper (I) iodide (19.38 mg, 0.102 mmol) in dioxane (1 mL) was heated at 100° C. for 8 hours. LCMS indicated the formation of desired product. The reaction mixture was filtered and the clear solution purified by prep. HPLC to give 1-(7-(3-(1,1-difluoroethyl)-1H-1,2,4-triazol-1-yl)-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 as white solid (53.4 mg, 47%). LCMS: m/e 543.97 (M+H)+, 1.56 min (method 2). 1H NMR (500 MHz, MeOD) δ ppm 2.13-2.33 (m, 3H) 2.85-3.09 (m, 2H) 3.72-4.04 (m, 5H) 4.93-5.11 (m, 2H) 7.30-7.67 (m, 3H) 7.82-8.08 (m, 3H) 8.33-8.57 (m, 2H) 8.75-8.93 (m, 1H) 9.43 (s, 1H).

Sources & evidence

ORD record
ord-5d20c163d9fd4e409ff077b7137da7cc
Source dataset
uspto-grants-2012_08
Patent number
US08242124B2

Reaction notes

Loading…