Piperidine → HCID 66599464, compound

HRID 2410854Notes

Reaction equation

HRID 2410854 reaction equation
[CH2:1]([N:8]1[C:16]2[CH:15]=[C:14]([O:17][CH3:18])[CH:13]=[CH:12][C:11]=2[C:10]2[N:19]=[C:20](Br)[CH:21]=[C:22]([C:23]([O:25][CH3:26])=[O:24])[C:9]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.C([O-])([O-])=O.[Cs+].[Cs+].[NH:76]1[CH2:81][CH2:80][CH2:79][CH2:78][CH2:77]1>CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd].O1CCOCC1>[CH2:1]([N:8]1[C:16]2[CH:15]=[C:14]([O:17][CH3:18])[CH:13]=[CH:12][C:11]=2[C:10]2[N:19]=[C:20]([N:76]3[CH2:81][CH2:80][CH2:79][CH2:78][CH2:77]3)[CH:21]=[C:22]([C:23]([O:25][CH3:26])=[O:24])[C:9]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 8082PiperidineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86663064HCID 86663064, compound

Product 1

HCID 66599464HCID 66599464, compoundYield 57.1%

Reagents, catalysts & solvents 3

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A vial containing a mixture of methyl 5-benzyl-2-bromo-7-methoxy-5H-pyrido[3,2-b]indole-4-carboxylate (90 mg, 0.21 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (18 mg, 0.032 mmol), tris(dibenzylideneacetone)dipalladium-chloroform adduct (11 mg, 11 μmol), Cs2CO3 (56 mg, 0.53 mmol) was flushed with nitrogen. Dioxane (1 mL) and piperidine (0.042 mL, 0.42 mmol) was added and the vial was sealed and heated at 100° C. overnight. This was then diluted with EtOAc, washed with water and brine, and dried over Na2SO4. Removal of the solvent followed by radial silica gel chromatography (step gradient elution with DCM containing 0 to 2% MeOH) afforded methyl 5-benzyl-7-methoxy-2-(piperidin-1-yl)-5H-pyrido[3,2-b]indole-4-carboxylate (51 mg, 0.12 mmol, 56% yield) as a solid. MS (ESI) m/z 430.2 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 8.15 (1H, d, J=8.55 Hz), 7.25 (1H, s), 7.15-7.21 (2H, m), 6.89-6.94 (3H, m), 6.87 (1H, dd, J=8.55, 2.14 Hz), 6.78 (1H, d, J=2.14 Hz), 5.59 (2H, s), 3.84 (3H, s), 3.66 (3H, s), 3.53-3.61 (4H, m), 1.68-1.76 (4H, m), 1.61-1.68 (2H, m).

Workup

  1. additionA vial containing
  2. customwas flushed with nitrogen
  3. customthe vial was sealed
  4. washwashed with water and brine
  5. dry with materialdried over Na2SO4
  6. customRemoval of the solvent
  7. washfollowed by radial silica gel chromatography (step gradient elution with DCM containing 0 to 2% MeOH)

Sources & evidence

ORD record
ord-84ba0ce988d445808cd58e3a796afc08
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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