Tetrahydrofuran → HCID 58790056, compound

HRID 418614Notes

Reaction equation

HRID 418614 reaction equation
Br[C:2]1[S:10][C:9]2[C:4](=[N:5][CH:6]=[CH:7][C:8]=2[O:11][C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=2[F:21])[CH:3]=1.[CH2:22]([N:24]([CH2:27][CH3:28])[CH2:25]C)C.[CH2:29]1COCC1>[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:21][C:13]1[CH:14]=[C:15]([N+:18]([O-:20])=[O:19])[CH:16]=[CH:17][C:12]=1[O:11][C:8]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:3]=[C:2]([C:29]#[C:28][CH2:27][N:24]([CH3:25])[CH3:22])[S:10][C:9]=12

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 594245212-Bromo-7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridine

Product 1

HCID 58790056HCID 58790056, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst

Procedure

To a solution of bromide 50 (3.0 g, 8.13 mmol) in THF (40 ml) was added 4-(prop-2-ynyl)dimethylamine (2.70 g, 32.5 mmol) [H-W. Tsou, et. al. J. Med. Chem., 2001, 44, 2719-2734], triethylamine (2.05 g, 2.5 eq, 20.3 mmol), CuI (154 mg, 0.1 eq, 0.813 mmol) and Pd(PPh3)2Cl2 (319 mg, 0.056 eq, 0.046 mmol). The reaction mixture was degassed with nitrogen and refluxed for 2 hrs, cooled to room temperature and adsorbed onto silica. Purification by column chromatography (eluent EtOAc to 20% MeOH in EtOAc) afforded 69 as a yellow solid (2.5 g, 83% yield). 1H NMR (DMSO-d6) δ (ppm): 8.65 (m, 1H), 8.48 (dd, J=2.74 and 10.56 Hz, 1H), 8.22 (m, 1H), 7.85 (s, 1H), 7.75 (m, 1H), 6.98 (d, J=5.28 Hz, 1H), 3.59 (s, 2H), 2.26 (s, 6H).

Workup

  1. customThe reaction mixture was degassed with nitrogen
  2. temperaturerefluxed for 2 hrs
  3. customPurification by column chromatography (eluent EtOAc to 20% MeOH in EtOAc)

Sources & evidence

ORD record
ord-63f01627509c46408fedbd53b79ffd4a
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Reaction notes

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