8-Hydroxyquinoline → tert-Butyl 8-(2-oxo-4-(6-(trifluoromethyl)pyridazin-3-yl)pyridin-1(2H)-yl)-6-tosyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate

HRID 474894Notes

Reaction equation

HRID 474894 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[N:8]=[N:7][C:6]([C:9]2[CH:14]=[CH:13][NH:12][C:11](=[O:15])[CH:10]=2)=[CH:5][CH:4]=1.Br[C:19]1[CH:20]=[CH:21][C:22]2[C:23]3[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38][C:24]=3[N:25]([S:28]([C:31]3[CH:37]=[CH:36][C:34]([CH3:35])=[CH:33][CH:32]=3)(=[O:30])=[O:29])[C:26]=2[CH:27]=1.OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[Cs+].[Cs+]>CS(C)=O.[Cu]I>[O:15]=[C:11]1[CH:10]=[C:9]([C:6]2[N:7]=[N:8][C:3]([C:2]([F:1])([F:16])[F:17])=[CH:4][CH:5]=2)[CH:14]=[CH:13][N:12]1[C:19]1[CH:20]=[CH:21][C:22]2[C:23]3[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38][C:24]=3[N:25]([S:28]([C:31]3[CH:32]=[CH:33][C:34]([CH3:35])=[CH:36][CH:37]=3)(=[O:30])=[O:29])[C:26]=2[CH:27]=1

Participants

7

Reactant 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 579502624-(6-(Trifluoromethyl)pyridazin-3-yl)pyridin-2(1H)-oneHCID 58093448tert-butyl 8-bromo-6-tosyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate

Product 1

HCID 66874789tert-Butyl 8-(2-oxo-4-(6-(trifluoromethyl)pyridazin-3-yl)pyridin-1(2H)-yl)-6-tosyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylateYield 44%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
135 °C

Procedure

A suspension of 4-(6-(trifluoromethyl)pyridazin-3-yl)pyridin-2(1H)-one (78 mg, 0.32 mmol), tert-butyl 8-bromo-6-tosyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (183 mg, 0.353 mmol), CuI (73 mg, 0.39 mmol), 8-hydroxyquinoline (9 mg, 0.06 mmol) and Cs2CO3 (115 mg, 0.353 mmol) in DMSO (10 mL) was degassed under reduced pressure for 45 min. The suspension was put under N2 and stirred at 135° C. overnight. The suspension was cooled, 9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added, and the resulting suspension was stirred at 25° C. for 30 min. The suspension was passed through a plug of silica gel, and the filtrate was washed with brine. The resulting solution was dried over Na2SO4 and concentrated under reduced pressure. Flash chromatography (silica gel, (1:1 EtOAc/hexanes)/(9:0.9:0.1 CH2Cl2/MeOH/NH4OH), 100:0 to 0:100) afforded the title compound (95 mg, 44%) as a yellow viscous oil: 1H NMR (300 MHz, CDCl3) δ 8.35 (br s, 1H), 8.12 (d, J=8.9 Hz, 1H), 7.99 (d, J=8.9 Hz, 1H), 7.71-7.63 (m, 4H), 7.54-7.47 (m, 1H), 7.39-7.22 (m, 4H), 3.73-3.58 (m, 4H), 3.44-3.31 (m, 2H), 2.95-2.86 (m, 2H), 2.37 (s, 3H), 1.47 (s, 9H).

Workup

  1. customwas degassed under reduced pressure for 45 min
  2. temperatureThe suspension was cooled
  3. addition9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added
  4. stirringthe resulting suspension was stirred at 25° C. for 30 min
  5. washthe filtrate was washed with brine
  6. dry with materialThe resulting solution was dried over Na2SO4
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f50faea0524e4c7bb97b32e2603547ff
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

Loading…