Methanol → HCID 59612443, compound

HRID 1890040Notes

Reaction equation

HRID 1890040 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:10]2[N:11]([N:15]=[C:16]([NH:18][C:19]3[CH:33]=[CH:32][C:22]4[CH2:23][CH2:24][N:25]([CH2:28][CH2:29]SC)[CH2:26][CH2:27][C:21]=4[CH:20]=3)[N:17]=2)[CH:12]=[CH:13][CH:14]=1.O[O:35][S:36]([O-:38])=O.[K+].[CH3:40]O>O>[CH3:40][S:36]([CH2:29][CH2:28][N:25]1[CH2:24][CH2:23][C:22]2[CH:32]=[CH:33][C:19]([NH:18][C:16]3[N:17]=[C:10]4[C:9]([C:4]5[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=5[O:2][CH3:1])=[CH:14][CH:13]=[CH:12][N:11]4[N:15]=3)=[CH:20][C:21]=2[CH2:27][CH2:26]1)(=[O:38])=[O:35]

Participants

5

Reactant 3

HCID 887MethanolHCID 23707502Potassium hydroxy sulfiteHCID 67481488HCID 67481488, compound

Product 1

HCID 59612443HCID 59612443, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To [8-(2-methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)-amine (0.256 g, 0.664 mmol) in N,N-dimethylformamide (10 mL) under an atmosphere of nitrogen was added potassium carbonate (0.275 g, 1.99 mmol), 2-chloroethyl methyl sulfide (0.0982 mL, 0.996 mmol), followed by sodium iodide (0.0996 g, 0.664 mmol) was heated at 70° C. overnight and cooled to room temperature. The reaction was diluted with ethyl acetate, washed with water several times, washed with brine, dried over sodium sulfate, and concentrated. The product was purified using Prep TLC plates (5% methanol in dichloromethane) and concentrated to give [8-(2-methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridine-2-yl]-[3-(2-methylsulfanyl-ethyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]-amine (0.173 g, 57%). MS=460 (MH)+. 314b) To [8-(2-methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridine-2-yl]-[3-(2-methylsulfanyl-ethyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]-amine (0.173 g, 0.376 mmol) in methanol (5 mL) was added oxone (0.694 g, 1.13 mmol) in water (2.5 mL) and was stirred at room temperature for 2 hours and concentrated. The reaction was partitioned between dichloromethane/1N sodium carbonate, washed with water/brine, dried over sodium sulfate, and concentrated. The product was purified using Prep TLC plates (5% methanol in dichloromethane) and concentrated to give [3-(2-methanesulfonyl-ethyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl]-[8-(2-methoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridine-2-yl]-amine (0.025 g, 14%). MP=91-94° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.52 (s, 1H), 8.75 (d, 1H), 7.55 (m, 2H), 7.40 (m, 2H), 7.32 (s, 1H), 7.18 (d, 1H), 7.05 (m, 3H), 3.75 (s, 3H), 3.28 (m, 2H), 3.18 (s, 3H), 2.85 (m, 2H), 2.75 (m, 4H), 2.58 (m, 4H): MS=492 (MH)+.

Workup

  1. concentrationconcentrated
  2. customThe reaction was partitioned between dichloromethane/1N sodium carbonate
  3. washwashed with water/brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe product was purified
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-cf18ee8c9d3741da99a6895f4dc7dd4d
Source dataset
uspto-grants-2013_08
Patent number
US08501936B2

Reaction notes

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