Bicarbonate Ion → (E)-5-(2-fluoro-1,2-di(pyridin-4-yl)vinyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1400569Notes

Reaction equation

HRID 1400569 reaction equation
[C:1]([N:3]1[C:11]2[CH:10]=[CH:9][C:8]([CH3:12])=[CH:7][C:6]=2[C:5]2[CH2:13][N:14]([CH3:17])[CH2:15][CH2:16][C:4]1=2)#[CH:2].Cl.Br[C:20]1[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=1.CCCC[N+:30]([CH2:39][CH2:40][CH2:41][CH3:42])([CH2:35]CCC)CCCC.[F-:43].C(=O)(O)[O-]>O>[F:43]/[C:2](/[C:41]1[CH:42]=[CH:35][N:30]=[CH:39][CH:40]=1)=[C:1](/[N:3]1[C:11]2[CH:10]=[CH:9][C:8]([CH3:12])=[CH:7][C:6]=2[C:5]2[CH2:13][N:14]([CH3:17])[CH2:15][CH2:16][C:4]1=2)\[C:20]1[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 769Bicarbonate IonHCID 881004-Bromopyridinium chlorideHCID 2724141Tetrabutylammonium FluorideHCID 594550005-Ethynyl-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 59455002(E)-5-(2-fluoro-1,2-di(pyridin-4-yl)vinyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 5-ethynyl-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (138 mg, 0.6 mmol), 4-bromopyridinehydrochloride (100 mg, 0.51 mmol), dichlorobistriphenyl phosphine palladium (II) (10 mg, 0.015 mmol) and TBAF.3H2O (481 mg, 1.5 mmol) were added to a reaction vessel and the contents heated at 80° C. (exothermicity observed; temperature 140° C.) for 5 min in microwave. After completion of the reaction (as monitored by TLC & LCMS) reaction mixture was poured into water (20 mL) and saturated bicarbonate solution was added. The desired compound was extracted with EtOAc (3×20 mL). The organic layer was washed with water (2×20 mL), dried over sodium sulfate and concentrated under vacuum to obtain crude product which was purified by reverse phase HPLC. 1H NMR (CDCl3, TFA salt) δ (ppm): 8.60 (d, 2H), 8.22 (d, 2H), 7.35 (d, 2H), 7.06 (s, 1H), 6.90 (d, 2H), 6.70 (d, 2H), 4.30 (m, 2H), 3.60 (m, 1H), 3.46 (m, 2H), 3.10 (m, 1H), 2.90 (s, 3H), 2.30 (s, 3H).

Workup

  1. addition3H2O (481 mg, 1.5 mmol) were added to a reaction vessel
  2. customAfter completion of the reaction (as monitored by TLC & LCMS) reaction mixture
  3. additionwas added
  4. extractionThe desired compound was extracted with EtOAc (3×20 mL)
  5. washThe organic layer was washed with water (2×20 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customto obtain crude product which
  9. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-edcaf8219bc249f7a671973ff4cd5c68
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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