Potassium Carbonate → 5-(3-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)phenyl)-N-methylpicolinamide

HRID 715197

Reaction equation

HRID 715197 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][NH:24][C:25](=[O:41])[C:26]1[CH:31]=[CH:30][C:29](B2OC(C)(C)C(C)(C)O2)=[CH:28][N:27]=1.C([O-])([O-])=O.[K+].[K+]>COCCOC.O.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]=[C:6]([C:29]4[CH:30]=[CH:31][C:26]([C:25]([NH:24][CH3:23])=[O:41])=[N:27][CH:28]=4)[CH:7]=[CH:2][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

6

Reactant 3

HCID 11430Potassium CarbonateHCID 44119560N-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinamideHCID 673785245-(3-bromophenyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 533734205-(3-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)phenyl)-N-methylpicolinamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a degassed solution of 5-(3-bromophenyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (101 mg, 0.286 mmol), N-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinamide (150 mg, 0.57 mmol) and K2CO3 (236 mg, 1.71 mmol) in DME-water (2:1) was added Pd(PPh3)4 (33 mg, 0.028 mmol). The reaction mixture was stirred at 90° C. for 45 min. The reaction mixture concentrated under reduced pressure. The residue was dissolved in EtOAc (50 mL) and washed with water (20 mL). The organic layer dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford crude material, which was purified by reverse phase HPLC to yield 5-(3-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)phenyl)-N-methylpicolinamide. 1H NMR (TFA salt, CD3OD) d (ppm): 8.97 (s, 1H), 8.23 (d, 1H), 8.12 (d, 1H), 7.85 (d, 1H), 7.78 (m, 2H), 7.5 (d, 1H), 7.37 (s, 1H), 7.21 (d, 1H), 7.04 (d, 1H), 4.76 (m, 1H), 4.4 (m, 1H), 3.8 (m, 1H), 3.6 (m, 1H), 3.08-3.21 (m, 5H), 3.0 (s, 3H), 2.4 (s, 3H).

Workup

  1. concentrationThe reaction mixture 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 dried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto afford crude material, which
  7. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-d33c44ae89784581affdc6e75d6b0d14
Source dataset
uspto-grants-2015_11
Patent number
US09187471B2

Linked notes

Loading…