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

HRID 1400570Notes

Reaction equation

HRID 1400570 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+](CCCC)(CCCC)CCCC.[F-:43].C(=O)(O)[O-]>O>[F:43]/[C:2](/[C:20]1[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=1)=[CH: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

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 59455145(Z)-5-(2-fluoro-2-(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), dichlorobistriphenylphosphine palladium (II) (10 mg, 0.015 mmol) and TBAF.3H2O (481 mg, 1.5 mmol) was added and heated at 80° C. (exothermicity observed; temperature 140° C.) for 5 min in microwave. After completion of 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) and the organic layer washed with water (2×20 mL), dried over sodium sulfate and concentrated under vacuum to obtain crude product that was purified by reverse phase HPLC. 1H NMR (CD3OD, TFA salt) δ (ppm): 8.78 (d, 2H), 8.18 (d, 2H), 7.62 (d, 1H), 7.40 (s, 1H), 7.28 (d, 1H), 6.42 (d, 1H), 4.75 (m, 1H), 4.40 (m, 1H), 3.90 (m, 1H), 3.60 (m, 1H), 3.40 (m, 2H), 3.18 (s, 3H), 2.44 (s, 3H).

Workup

  1. addition3H2O (481 mg, 1.5 mmol) was added
  2. customAfter completion of 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 washed with water (2×20 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customto obtain crude product that
  9. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-910a65e2591e4fa0870a886f1a7f3ca5
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

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