Potassium Phosphate, Tribasic → 2,8-dimethyl-5-thiazol-4-yl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 715167Notes

Reaction equation

HRID 715167 reaction equation
[CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.Br[C:17]1[N:18]=[CH:19][S:20][CH:21]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].N1CCC[C@H]1C(O)=O>CN(C=O)C.O.[Cu]I>[CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[N:6]([C:17]3[N:18]=[CH:19][S:20][CH:21]=3)[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 2092911H-Pyrido[4,3-b]indole, 2,3,4,5-tetrahydro-2,8-dimethyl-HCID 27632184-Bromothiazole

Product 1

HCID 673792532,8-dimethyl-5-thiazol-4-yl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoleYield 20.8%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (0.2 g, 1 mmol), 4-bromo-thiazole (0.246 g, 1.5 mmol), K3PO4 (0.636 g, 3 mmol), CuI (19 mg, 0.1 mmol) and L-Proline (23 mg, 0.2 mmol) in dry DMF (5 mL) was stirred at 150° C. for 16 h. The reaction mixture was diluted with water and extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford crude material, which was purified by reverse phase HPLC to yield 2,8-dimethyl-5-thiazol-4-yl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (59 mg). 1H NMR (TFA salt, CD3OD) d (ppm): 9.10 (s, 1H), 7.62 (s, 1H), 7.38 (d, 1H), 7.30 (s, 1H), 7.10 (d, 1H), 4.70 (d, 1H), 4.30 (d, 1H), 3.80 (m, 1H), 3.50 (m, 1H), 3.26 (m, 1H), 3.18 (s, 3H), 3.16 (m, 1H), 2.42 (s, 3H).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto afford crude material, which
  5. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-2095b581a745404aaadf64825cdec63c
Source dataset
uspto-grants-2015_11
Patent number
US09187471B2

Reaction notes

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