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

HRID 1803280Notes

Reaction equation

HRID 1803280 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[C:30]([CH3:31])=[N:29][CH:28]=[N:27]3)=[C:22]([F:32])[CH:21]=2)[N:15]=1)[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1.[I-].[Na+]>CC(C)=O>[F:32][C:22]1[CH:21]=[C:20]([NH:19][C:16]2[N:15]=[C:14]3[CH:6]([C:7]4[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=4)[CH2:5][CH2:4][CH2:3][CH2:2][N:18]3[N:17]=2)[CH:25]=[CH:24][C:23]=1[N:26]1[C:30]([CH3:31])=[N:29][CH:28]=[N:27]1

Participants

4

Reactant 2

HCID 5238Sodium IodideHCID 668588295-(5-chloro-1-(4-fluorophenyl)pentyl)-N-(3-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine

Product 1

HCID 58110121N-(3-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)phenyl)-9-(4-fluorophenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-amineYield 31.7%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of 5-(5-chloro-1-(4-fluorophenyl)pentyl)-N-(3-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine (230 mg, 0.502 mmol), sodium iodide (376 mg, 2.51 mmol), and diisoproplylethylamine (0.088 mL, 0.50 mmol) in acetone (10 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 (10-80% EtOAc/chloroform, linear gradient) to afford 67 mg (30% yield) of the titled compound as a pink solid. LC-MS (M+H)+ 422.3. 1H NMR (500 MHz, chloroform-d) δ ppm 7.93 (s, 1H) 7.65 (dd, J=12.51, 2.44 Hz, 1H) 721-7.24 (m, 1H) 7.09-7.16 (m, 2H) 6.99-7.08 (m, 3H) 6.90 (s, 1H) 4.21-4.31 (m, 3H) 2.37 (s, 3H) 2.15-2.26 (m, 1H) 2.03-2.12 (m, 1H) 1.81-2.01 (m, 4H).

Workup

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

Sources & evidence

ORD record
ord-f471c3088dc24226831ee5fa743da9a3
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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