Sodium Iodide → N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-9-(3,4,5-trifluorophenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-amine

HRID 1803253Notes

Reaction equation

HRID 1803253 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]([C:16]1[NH:20][N:19]=[C:18]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([N:28]3[CH:32]=[C:31]([Cl:33])[N:30]=[CH:29]3)=[C:24]([O:34][CH3:35])[CH:23]=2)[N:17]=1)[C:7]1[CH:12]=[C:11]([F:13])[C:10]([F:14])=[C:9]([F:15])[CH:8]=1.[I-].[Na+]>CC(C)=O>[Cl:33][C:31]1[N:30]=[CH:29][N:28]([C:25]2[CH:26]=[CH:27][C:22]([NH:21][C:18]3[N:17]=[C:16]4[CH:6]([C:7]5[CH:12]=[C:11]([F:13])[C:10]([F:14])=[C:9]([F:15])[CH:8]=5)[CH2:5][CH2:4][CH2:3][CH2:2][N:20]4[N:19]=3)=[CH:23][C:24]=2[O:34][CH3:35])[CH:32]=1

Participants

4

Reactant 2

HCID 5238Sodium IodideHCID 668590005-(5-chloro-1-(3,4,5-trifluorophenyl)pentyl)-N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-1H-1,2,4-triazol-3-amine

Product 1

HCID 58110127N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-9-(3,4,5-trifluorophenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-amineYield 17%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of 5-(5-chloro-1-(3,4,5-trifluorophenyl)pentyl)-N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-1H-1,2,4-triazol-3-amine (2.66 g, 5.06 mmol), sodium iodide (3.79 g, 25.3 mmol), and diisoproplylethylamine (1.77 mL, 10.1 mmol) in acetone (40 mL) was heated in a sealed vessel at 100° C. for 2 h. The reaction was concentrated in vacuo. The crude product was purified using silica gel column chromatography (35-50% EtOAc/chloroform, linear gradient) to afford 420 mg (17% yield) of the titled compound as a pale yellow solid. The solid was recrystallized from EtOH to afford an analytical sample. LC-MS (M+H)+ 489.2. 1H NMR (500 MHz, chloroform-d) δ ppm 7.52 (d, J=1.53 Hz, 1 H) 7.39 (d, J=2.14 Hz, 1H) 7.11 (d, J=8.55 Hz, 1 H) 7.03 (d, J=1.22 Hz, 1H) 6.79-6.92 (m, 3 H) 6.59 (s, 1 H) 4.24-4.35 (m, 1 H) 4.10-4.24 (m, 2 H) 3.82 (s, 3H) 1.94-2.20 (m, 4 H) 1.78-1.94 (m, 2 H).

Workup

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

Sources & evidence

ORD record
ord-fbd950d44cf94480a582a738d123b735
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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