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

HRID 1803256Notes

Reaction equation

HRID 1803256 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]([C:14]1[NH:18][N:17]=[C:16]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([N:26]3[CH:30]=[C:29]([Cl:31])[N:28]=[CH:27]3)=[C:22]([O:32][CH3:33])[CH:21]=2)[N:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[F:13].[I-].[Na+]>CC(C)=O>[Cl:31][C:29]1[N:28]=[CH:27][N:26]([C:23]2[CH:24]=[CH:25][C:20]([NH:19][C:16]3[N:15]=[C:14]4[CH:6]([C:7]5[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=5[F:13])[CH2:5][CH2:4][CH2:3][CH2:2][N:18]4[N:17]=3)=[CH:21][C:22]=2[O:32][CH3:33])[CH:30]=1

Participants

4

Reactant 2

HCID 5238Sodium IodideHCID 668589545-(5-chloro-1-(2-fluorophenyl)pentyl)-N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-1H-1,2,4-triazol-3-amine

Product 1

HCID 46864955N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-9-(2-fluorophenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-amineYield 10.2%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of 5-(5-chloro-1-(2-fluorophenyl)pentyl)-N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-1H-1,2,4-triazol-3-amine (2.47 g, 5.05 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 (0-35% EtOAc/chloroform, linear gradient) to afford 234 mg (10% 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)+ 453.3. 1H NMR (500 MHz, chloroform-d) δ ppm 7.50 (d, J=1.53 Hz, 1 H) 7.44 (d, J=2.14 Hz, 1 H) 7.27-7.34 (m, 1 H) 7.21-7.26 (m, 1 H) 7.16 (t, J=7.17 Hz, 1 H) 7.04-7.13 (m, 2 H) 7.01 (d, J=1.53 Hz, 1 H) 6.76 (dd, J=8.39, 2.29 Hz, 1 H) 6.60 (s, 1 H) 4.38-4.48 (m, 2 H) 4.22 (dd, J=14.50, 9.92 Hz, 1 H) 3.74 (s, 3H) 2.00-2.27 (m, 4H) 1.79-1.94 (m, 2 H).

Workup

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

Sources & evidence

ORD record
ord-806b252200e645669663279c137d857e
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

Loading…