Sodium Iodide → N-(3-fluoro-5-methoxy-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 1803327Notes

Reaction equation

HRID 1803327 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]([O:30][CH3:31])[C:27]([N:32]3[CH:36]=[N:35][C:34]([CH3:37])=[N:33]3)=[C:26]([F:38])[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:38][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]([O:30][CH3:31])[C:27]=1[N:32]1[CH:36]=[N:35][C:34]([CH3:37])=[N:33]1

Participants

5

Reactant 3

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 668599225-(5-chloro-1-(4-(trifluoromethoxy)phenyl)pentyl)-N-(3-fluoro-5-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine

Product 1

HCID 58110060N-(3-fluoro-5-methoxy-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 45.6%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of 5-(5-chloro-1-(4-(trifluoromethoxy)phenyl)pentyl)-N-(3-fluoro-5-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine (753 mg, 1.36 mmol), sodium iodide (1.02 g, 6.80 mmol), and diisopropylethylamine (1.19 mL, 6.80 mmol) in acetone (30 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 (50% EtOAc/chloroform) to afford 321 mg (44% yield) of the titled compound as a white solid. LC-MS (M+H)+ 518.3. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.02 (s, 1 H), 7.20 (s, 4 H), 6.90-6.96 (m, 2 H), 6.73 (s, 1 H), 4.17-4.34 (m, 3 H), 3.72 (s, 3 H), 2.47 (s, 3 H), 2.13-2.26 (m, 1 H), 2.05-2.13 (m, 1 H), 1.92-2.04 (m, 2 H), 1.82-1.92 (m, 2 H).

Workup

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

Sources & evidence

ORD record
ord-478f4edb2ac846fcbf2cf2010f6569a6
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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