Tetrabutylammonium Fluoride → 4-[2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-2-fluoro-vinyl]-2-fluoro-N-methyl-benzamide

HRID 1400567Notes

Reaction equation

HRID 1400567 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].Br[C:19]1[CH:28]=[CH:27][C:22]([C:23]([NH:25][CH3:26])=[O:24])=[C:21]([F:29])[CH:20]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-:47]>O>[CH3:17][N:14]1[CH2:15][CH2:16][C:4]2[N:3]([C:1]([F:47])=[CH:2][C:19]3[CH:28]=[CH:27][C:22]([C:23]([NH:25][CH3:26])=[O:24])=[C:21]([F:29])[CH:20]=3)[C:11]3[CH:10]=[CH:9][C:8]([CH3:12])=[CH:7][C:6]=3[C:5]=2[CH2:13]1

Participants

5

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 24694329Benzamide, 4-bromo-2-fluoro-N-methyl-HCID 594550005-Ethynyl-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 673110924-[2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-2-fluoro-vinyl]-2-fluoro-N-methyl-benzamide

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5-ethynyl-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (268 mg, 1.2 mmol), 4-bromo-2-fluoro-N-methyl-benzamide (230 mg, 1.0 mmol), dichlorobistriphenyl phosphinepalladium (II) (21 mg, 0.03 mmol) and TBAF.3H2O (945 mg, 3.0 mmol) were added to a reaction vessel and the contents heated at 80° C. for 5 min in microwave. After completion of reaction (as monitored by TLC & LCMS), the reaction mixture was poured into water (25 mL) and the compound extracted with EtOAc (3×60 mL). The combined organic layers were dried over sodium sulfate, concentrated under vacuum and purified by reverse phase chromatography to obtain 22 mg of 4-[2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-2-fluoro-vinyl]-2-fluoro-N-methyl-benzamide and 63 mg of product. 1H NMR (CD3OD, oxalate salt) δ (ppm): 8.30 (m, 1H), 8.80 (t, 1H), 7.50 (t, 1H), 7.38-7.24 (m, 3H), 7.10 (d, 1H), 6.80 (m, 2H), 4.50 (m, 2H), 3.60 (m, 2H), 3.25 (m, 2H), 3.04 (s, 3H), 2.96 (d, 3H), 2.82 (s, 3H), 2.40 (s, 3H).

Workup

  1. addition3H2O (945 mg, 3.0 mmol) were added to a reaction vessel
  2. customAfter completion of reaction (as monitored by TLC & LCMS)
  3. extractionthe compound extracted with EtOAc (3×60 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. concentrationconcentrated under vacuum
  6. custompurified by reverse phase chromatography

Sources & evidence

ORD record
ord-075c42741de446c28537509bc681b200
Source dataset
uspto-grants-2014_12
Patent number
US08906925B2

Reaction notes

Loading…