Sodium Iodide → [8-(2-ethoxy-5-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[3-(2-methanesulfonyl-ethyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)-amine

HRID 1890045Notes

Reaction equation

HRID 1890045 reaction equation
[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:5]=1[C:14]1[C:15]2[N:16]([N:20]=[C:21]([NH:23][C:24]3[CH:34]=[CH:33][C:27]4[CH2:28][CH2:29][NH:30][CH2:31][CH2:32][C:26]=4[CH:25]=3)[N:22]=2)[CH:17]=[CH:18][CH:19]=1)[CH3:2].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:42][CH2:43][S:44]([CH3:47])(=[O:46])=[O:45].[I-].[Na+]>CN(C)C=O.C(OCC)(=O)C>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]([F:12])([F:11])[F:13])=[CH:6][C:5]=1[C:14]1[C:15]2[N:16]([N:20]=[C:21]([NH:23][C:24]3[CH:34]=[CH:33][C:27]4[CH2:28][CH2:29][N:30]([CH2:42][CH2:43][S:44]([CH3:47])(=[O:46])=[O:45])[CH2:31][CH2:32][C:26]=4[CH:25]=3)[N:22]=2)[CH:17]=[CH:18][CH:19]=1)[CH3:2]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 3035331-Chloro-2-methanesulfonylethaneHCID 59612549[8-(2-ethoxy-5-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridine-2-yl]-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)-amine

Product 1

HCID 59612422[8-(2-ethoxy-5-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[3-(2-methanesulfonyl-ethyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)-amineYield 57%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To 2-chloroethyl methyl sulfide (0.891 mL, 9.04 mmol) in methanol (10 mL) was added oxone (11.12 g, 18.08 mmol) in water (5 mL) and the reaction was stirred at room temperature overnight and concentrated. The reaction was partitioned between dichloromethane/1N sodium carbonate, washed with water/brine, dried over sodium sulfate, and concentrated to give 1-chloro-2-methanesulfonyl-ethane (1.17 g, 91%). 320b) To [8-(2-ethoxy-5-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridine-2-yl]-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)-amine (0.200 g, 0.428 mmol) in N,N-dimethylformamide (5 mL) was added potassium carbonate (0.177 g, 1.28 mmol), 1-chloro-2-methanesulfonyl-ethane (0.122 g, 0.856 mmol), followed by sodium iodide (0.0641 g, 0.428 mmol) and was heated at 80° C. overnight and cooled at r.t. The reaction was diluted with ethyl acetate, washed with water several times, dried over sodium sulfate, and concentrated. The product was purified using Prep TLC plates (5% methanol in dichloromethane) and concentrated to give [8-(2-ethoxy-5-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-[3-(2-methanesulfonyl-ethyl)-2,3,4,5-tetrahydro-1H-3-benzazepin-7yl)-amine (0.140 g, 57%). MP=105-109° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 9.51 (s, 1H), 8.78 (d, 1H), 7.98 (s, 1H), 7.78 (d, 1H), 7.68 (d, 1H), 7.40 (m, 3H), 7.08 (t, 1H), 6.95 (d, 1H), 4.15 (q, 2H), 3.28 (m, 2H), 3.05 (s, 3H), 2.85 (m, 2H), 2.75 (m, 4H), 2.55 (m, 4H), 1.22 (t, 3H): MS=574 (MH)+.

Workup

  1. temperaturecooled at r.t
  2. washwashed with water several times
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe product was purified
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-bb7dd6c3f02e4e4296fba326c993cb19
Source dataset
uspto-grants-2013_08
Patent number
US08501936B2

Reaction notes

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