Sodium Iodide → N-(3,5-difluoro-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-9-(4-(trifluoromethoxy)phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-amine

HRID 1803287Notes

Reaction equation

HRID 1803287 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]([C:18]1[NH:22][N:21]=[C:20]([NH:23][C:24]2[CH:29]=[C:28]([F:30])[C:27]([N:31]3[CH:35]=[N:34][C:33]([CH3:36])=[N:32]3)=[C:26]([F:37])[CH:25]=2)[N:19]=1)[C:7]1[CH:12]=[CH:11][C:10]([O:13][C:14]([F:17])([F:16])[F:15])=[CH:9][CH:8]=1.[I-].[Na+].C(N(C(C)C)CC)(C)C>CC(C)=O>[F:37][C:26]1[CH:25]=[C:24]([NH:23][C:20]2[N:19]=[C:18]3[CH:6]([C:7]4[CH:12]=[CH:11][C:10]([O:13][C:14]([F:17])([F:16])[F:15])=[CH:9][CH:8]=4)[CH2:5][CH2:4][CH2:3][CH2:2][N:22]3[N:21]=2)[CH:29]=[C:28]([F:30])[C:27]=1[N:31]1[CH:35]=[N:34][C:33]([CH3:36])=[N:32]1

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 866499315-(5-chloro-1-(4-(trifluoromethoxy)phenyl)pentyl)-N-(3,5-difluoro-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine

Product 1

HCID 58110013N-(3,5-difluoro-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-9-(4-(trifluoromethoxy)phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-amineYield 34.4%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of 5-(5-chloro-1-(4-(trifluoromethoxy)phenyl)pentyl)-N-(3,5-difluoro-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine (1.24 g, 2.30 mmol), sodium iodide (1.72 g, 11.5 mmol), and diisopropylethylamine (2.00 mL, 11.5 mmol) in acetone (50 mL) was heated in a sealed vessel at 100° C. for 6 h. The reaction was concentrated in vacuo. The crude product was purified using silica gel column chromatography (70% EtOAc/chloroform) to afford 400 mg of the titled compound. The solid was recrystallized from EtOAc/Hex to afford 230 mg (19% yield) of the titled compound as a crystalline white solid. LC-MS (M+H)+ 506.1. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.11 (1H, s), 7.13-7.23 (6H, m), 6.92 (1 H, s), 4.22-4.33 (3 H, m), 2.49 (3 H, s), 2.15-2.27 (1 H, m), 2.05-2.13 (1H, m), 1.92-2.01 (2 H, m, J=14.8, 9.8, 7.2, 7.2 Hz), 1.82-1.90 (2 H, m).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customThe crude product was purified

Sources & evidence

ORD record
ord-af929638759f4039b53ea2814e08efe7
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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