8-Hydroxyquinoline → tert-Butyl 6-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-9-methyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate

HRID 930663Notes

Reaction equation

HRID 930663 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:20][CH2:19][C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15](Br)[CH:16]=3)[N:11]([CH3:22])[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:23]([O:30][C:31]1[CH:36]=[CH:35][NH:34][C:33](=[O:37])[CH:32]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[K+].[K+].[NH4+].[OH-]>CS(C)=O.C(Cl)Cl.[Cu]I.CO>[CH2:23]([O:30][C:31]1[CH:36]=[CH:35][N:34]([C:15]2[CH:16]=[C:17]3[C:12](=[CH:13][CH:14]=2)[N:11]([CH3:22])[C:10]2[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:20][CH2:19][C:18]3=2)[C:33](=[O:37])[CH:32]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

10

Reactant 5

HCID 19238-HydroxyquinolineHCID 11430Potassium CarbonateHCID 14923Ammonium HydroxideHCID 36077244-Benzyloxy-2(1H)-pyridoneHCID 57950425HCID 57950425, compound

Product 1

HCID 57950451tert-Butyl 6-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-9-methyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylateYield 34.5%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
130 °C

Procedure

A solution of tert-Butyl-6-bromo-9-methyl-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate (750 mg, 2.03 mmol) in DMSO (10 mL) was stirred under nitrogen and treated sequentially with 4-(benzyloxy)pyridin-2(1H)-one (448 mg, 2.23 mmol), 8-hydroxyquinoline (44 mg, 0.305 mmol), CuI (58 mg, 0.305 mmol) and K2CO3 (308 mg, 2.23 mmol). After stirring overnight at 130° C., the mixture was allowed to cool to room temperature and a mixture of MeOH and NH4OH (10:1, 10 mL) was added. After stirring for 15 min, the mixture was diluted with CH2Cl2, washed with brine, dried over Na2SO4, filtered and concentrated to dryness. Purification by flash column chromatography (40 g ISCO column eluting with a 1:1 ethylacetate/hexanes and a methanol/ammonia mixture (10:1); gradient 100% 1:1 ethylacetate/hexanes to 90% 1:1 ethylacetate/hexanes/10% methanol/ammonia mixture (10:1) over 30 min at 25 mL/min) provided the title compound (340 mg, 33%) as a yellow solid; 1H NMR (500 MHz, CDCl3) δ 7.50-7.36 (m, 8H), 7.13 (d, J=7.8, Hz, 1H), 6.09 (d, J=2.6 Hz, 1H), 6.03 (dd, J=7.5, 2.7 Hz, 1H), 5.05 (s, 2H), 4.65 (br s, 2H), 3.73 (br s, 2H), 3.66 (s, 3H), 2.77 (br s, 2H), 1.51 (s, 9H).

Workup

  1. temperatureto cool to room temperature
  2. additionwas added
  3. stirringAfter stirring for 15 min
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customPurification by flash column chromatography (40 g ISCO column
  9. washeluting with a 1:1 ethylacetate/hexanes

Sources & evidence

ORD record
ord-cf9a2ae593b046edbfdfdf074f7a0443
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Reaction notes

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