Water → 2,8-dimethyl-5-(3-(1-methyl-1H-indol-5-yl)phenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 715180Notes

Reaction equation

HRID 715180 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:8]2[C:16]3[CH:15]=[CH:14][C:13]([CH3:17])=[CH:12][C:11]=3[C:10]3[CH2:18][N:19]([CH3:22])[CH2:20][CH2:21][C:9]2=3)[CH:5]=[CH:6][CH:7]=1.[CH3:23][N:24]1[C:32]2[C:27](=[CH:28][C:29](B3OC(C)(C)C(C)(C)O3)=[CH:30][CH:31]=2)[CH:26]=[CH:25]1.C([O-])([O-])=O.[K+].[K+].O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:22][N:19]1[CH2:20][CH2:21][C:9]2[N:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([C:29]4[CH:28]=[C:27]5[C:32](=[CH:31][CH:30]=4)[N:24]([CH3:23])[CH:25]=[CH:26]5)[CH:3]=3)[C:16]3[CH:15]=[CH:14][C:13]([CH3:17])=[CH:12][C:11]=3[C:10]=2[CH2:18]1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 162177781-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indoleHCID 673785245-(3-bromophenyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 673787012,8-dimethyl-5-(3-(1-methyl-1H-indol-5-yl)phenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a de-aerated solution of 5-(3-bromophenyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (100 mg, 0.281 mmol), 1-methylindole-5-boronic acid pinacol ester (144 mg, 0.560 mmol) and K2CO3 (116 mg, 0.845 mmol) in DME (4 mL)-water (2 mL) was added Pd(PPh3)4 (16 mg, 0.013 mmol). The reaction mixture was stirred at 90° C. for 45 min. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in EtOAc (50 mL) and washed with water (20 mL). The organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure to obtain crude, which was purified by reverse phase HPLC to yield 2,8-dimethyl-5-(3-(1-methyl-1H-indol-5-yl)phenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole. 1H NMR (TFA salt, CD3OD) d (ppm): 7.82 (s, 1H), 7.8 (d, 1H), 7.62 (dd, 2H), 7.46 (dd, 2H), 7.35 (m, 2H), 7.2 (m, 2H), 7.04 (d, 1H), 6.5 (d, 1H), 4.6 (m, 2H), 3.8 (s, 3H), 3.7 (m, 2H), 3.11 (m, 5H), 2.41 (s, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in EtOAc (50 mL)
  3. washwashed with water (20 mL)
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto obtain crude, which
  7. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-1ca65d6d03ac4e5482778c340437690c
Source dataset
uspto-grants-2015_11
Patent number
US09187471B2

Reaction notes

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