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

HRID 1803324Notes

Reaction equation

HRID 1803324 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]=[CH:28][C:27]([N:30]3[CH:34]=[C:33]([Cl:35])[N:32]=[CH:31]3)=[C:26]([O:36][CH3:37])[CH:25]=2)[N:19]=1)[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH:15]([F:17])[F:16])=[CH:9][CH:8]=1.[I-].[Na+]>CC(C)=O>[Cl:35][C:33]1[N:32]=[CH:31][N:30]([C:27]2[CH:28]=[CH:29][C:24]([NH:23][C:20]3[N:19]=[C:18]4[CH:6]([C:7]5[CH:12]=[CH:11][C:10]([O:13][CH2:14][CH:15]([F:17])[F:16])=[CH:9][CH:8]=5)[CH2:5][CH2:4][CH2:3][CH2:2][N:22]4[N:21]=3)=[CH:25][C:26]=2[O:36][CH3:37])[CH:34]=1

Participants

4

Reactant 2

HCID 5238Sodium IodideHCID 866499405-(5-chloro-1-(4-(2,2-difluoroethoxy)phenyl)pentyl)-N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-1H-1,2,4-triazol-3-amine

Product 1

HCID 58110154N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-9-(4-(2,2-difluoroethoxy)phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-amineYield 20%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of 5-(5-chloro-1-(4-(2,2-difluoroethoxy)phenyl)pentyl)-N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-1H-1,2,4-triazol-3-amine (1.44 g, 2.61 mmol, sodium iodide (1.96 g, 13.1 mmol), and diisoproplylethylamine (2.28 mL, 13.1 mmol) in acetone (30 mL) was heated in a sealed vessel at 100° C. for 16 h. The reaction was concentrated in vacuo. The crude product was purified using silica gel column chromatography (50% EtOAc/chloroform). The purified product was recrystallized from EtOAc/hexane to afford 279 mg (20% yield) of the titled compound as an off-white crystalline white solid. LC-MS (M+H)+ 515.3. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.51 (d, J=1.5 Hz, 1 H), 7.42 (d, J=2.4 Hz, 1 H), 7.12 (d, J=8.9 Hz, 2 H), 7.09 (d, J=8.5 Hz, 1 H), 7.02 (d, J=1.5 Hz, 1 H), 6.92 (d, J=8.5 Hz, 2 H), 6.84 (dd, J=8.4, 2.3 Hz, 1 H), 6.67 (s, 1 H), 6.10 (tt, J=55.1, 4.1 Hz, 1 H), 4.26 (d, J=8.5 Hz, 1 H), 4.15-4.25 (m, 4 H), 3.80 (s, 3 H), 2.16-2.30 (m, 1 H), 2.05-2.13 (m, 1 H), 1.83-2.02 (m, 4 H).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customThe crude product was purified
  3. customThe purified product was recrystallized from EtOAc/hexane

Sources & evidence

ORD record
ord-d9b577390451445a92623af20dc57800
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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