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

HRID 1803293Notes

Reaction equation

HRID 1803293 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]([C:19]1[NH:23][N:22]=[C:21]([NH:24][C:25]2[CH:30]=[C:29]([F:31])[C:28]([N:32]3[CH:36]=[N:35][C:34]([CH3:37])=[N:33]3)=[CH:27][CH:26]=2)[N:20]=1)[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][C:15]([F:18])([F:17])[F:16])=[CH:9][CH:8]=1.[I-].[Na+]>CC(C)=O>[F:31][C:29]1[CH:30]=[C:25]([NH:24][C:21]2[N:20]=[C:19]3[CH:6]([C:7]4[CH:12]=[CH:11][C:10]([O:13][CH2:14][C:15]([F:18])([F:17])[F:16])=[CH:9][CH:8]=4)[CH2:5][CH2:4][CH2:3][CH2:2][N:23]3[N:22]=2)[CH:26]=[CH:27][C:28]=1[N:32]1[CH:36]=[N:35][C:34]([CH3:37])=[N:33]1

Participants

4

Reactant 2

HCID 5238Sodium IodideHCID 668609835-(5-chloro-1-(4-(2,2,2-trifluoroethoxy)phenyl)pentyl)-N-(5-fluoro-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine

Product 1

HCID 58110083N-(3-fluoro-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-9-(4-(2,2,2-trifluoroethoxy)phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-amineYield 50.1%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of 5-(5-chloro-1-(4-(2,2,2-trifluoroethoxy)phenyl)pentyl)-N-(5-fluoro-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine (1.03 g, 1.91 mmol), sodium iodide (1.43 g, 9.54 mmol), and diisoproplylethylamine (0.1.67 mL, 9.54 mmol) in acetone (10 mL) was heated in a sealed vessel at 100° C. for 4 h. The reaction was concentrated in vacuo. The crude product was purified using silica gel column chromatography (50% EtOAc/chloroform) to afford 480 mg (48% yield) of the titled compound as an off-white solid. This material was recrystallized from EtOH to afford 225 mg (23% yield) of the titled compound as a crystalline white solid, LC-MS (M+H)+ 502.4. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.39 (d, J=2.1 Hz, 1 H), 7.69 (dd, J=13.7, 2.1 Hz, 1 H), 7.60 (t, J=8.7 Hz, 1 H), 7.13 (d, J=8.2 Hz, 2 H), 7.01 (d, J=8.9 Hz, 1H), 6.95 (d, J=8.5 Hz, 2H), 6.80 (s, 1 H), 4.36 (q, J=8.2 Hz, 2 H), 4.28 (d, J=7.3 Hz, 1 H), 4.21-4.26 (m, 2 H), 2.50 (s, 3 H), 2.17-2.28 (m, 1 H), 2.04-2.14 (m, 1 H), 1.84-2.03 (m, 4 H).

Workup

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

Sources & evidence

ORD record
ord-951aeb78c73244529fb79a362c56bc0c
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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