4-Bromothiazole → 5-(2-Fluoro-2-thiazol-4-yl-vinyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indole

HRID 1401649Notes

Reaction equation

HRID 1401649 reaction equation
Br[C:2]1[N:3]=[CH:4][S:5][CH:6]=1.[C:7]([N:9]1[C:17]2[CH:16]=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=2[C:11]2[CH2:19][N:20]([CH3:23])[CH2:21][CH2:22][C:10]1=2)#[CH:8].O.O.O.[F-:27].C([N+](CCCC)(CCCC)CCCC)CCC>O>[F:27][C:8]([C:2]1[N:3]=[CH:4][S:5][CH:6]=1)=[CH:7][N:9]1[C:17]2[CH:16]=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=2[C:11]2[CH2:19][N:20]([CH3:23])[CH2:21][CH2:22][C:10]1=2

Participants

5

Reactant 3

HCID 27632184-BromothiazoleHCID 11726816Tetrabutylammonium Fluoride TrihydrateHCID 594550005-Ethynyl-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 673101855-(2-Fluoro-2-thiazol-4-yl-vinyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indoleYield 3.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

4-Bromothiazole (100 mg, 0.609 mmol), 5-ethynyl-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 163 mg, 0.731 mmol), dichlorobistrifluorophosphine palladium (12 mg, 0.01 mmol) and tetrabutylammonium fluoride trihydrate (575 mg, 1.827 mmol) were charged in a microwave vial and heated to 85° C. for 5 min in microwave oven. On completion of reaction (as observed by LCMS), the reaction mixture was poured into 20 mL water and compound extracted with EtOAc (3×50 mL). The combined organic layers were washed with water (2×50 mL) and dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (190 mg) obtained was purified by reverse phase chromatography to afford 7 mg of 5-(2-Fluoro-2-thiazol-4-yl-vinyl)-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole. 1H NMR (CDCl3, free base) δ (ppm): 8.80 (s, 1H), 7.60 (s, 1H), 7.38 (d, 1H), 7.18 (s, 1H), 7.05 (d, 1H), 6.22 (d, 1H), 3.80 (m, 2H), 3.0 (m, 4H), 3.62 (s, 3H), 2.40 (s, 3H).

Workup

  1. customOn completion of reaction (as observed by LCMS)
  2. extractionextracted with EtOAc (3×50 mL)
  3. washThe combined organic layers were washed with water (2×50 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe crude product (190 mg) obtained
  7. customwas purified by reverse phase chromatography

Sources & evidence

ORD record
ord-3e6f0213bc55472bac304b9cc0edff10
Source dataset
uspto-grants-2014_12
Patent number
US08907097B2

Reaction notes

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