Sodium Iodide → N-(2-fluoro-5-methoxy-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 1803295Notes

Reaction equation

HRID 1803295 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]([O:31][CH3:32])[C:28]([N:33]3[CH:37]=[N:36][C:35]([CH3:38])=[N:34]3)=[CH:27][C:26]=2[F:39])[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:39][C:26]1[CH:27]=[C:28]([N:33]2[CH:37]=[N:36][C:35]([CH3:38])=[N:34]2)[C:29]([O:31][CH3:32])=[CH:30][C:25]=1[NH:24][C:21]1[N:20]=[C:19]2[CH:6]([C:7]3[CH:12]=[CH:11][C:10]([O:13][CH2:14][C:15]([F:18])([F:17])[F:16])=[CH:9][CH:8]=3)[CH2:5][CH2:4][CH2:3][CH2:2][N:23]2[N:22]=1

Participants

4

Reactant 2

HCID 5238Sodium IodideHCID 668583335-(5-chloro-1-(4-(2,2,2-trifluoroethoxy)phenyl)pentyl)-N-(2-fluoro-5-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine

Product 1

HCID 58110130N-(2-fluoro-5-methoxy-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 25.2%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of 5-(5-chloro-1-(4-(2,2,2-trifluoroethoxy)phenyl)pentyl)-N-(2-fluoro-5-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine (2.01 g, 3.54 mmol), sodium iodide (2.65 g, 17.7 mmol), and diisoproplylethylamine (1.55 mL, 8.85 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 474 mg (25% yield) of the titled compound as an off-white solid. LC-MS (M+H)+ 532.5. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 8.55 (s, 1 H), 8.11 (d, J=7.6 Hz, 1 H), 7.47 (d, J=11.6 Hz, 1 H), 7.16 (d, J=8.5 Hz, 2 H), 6.95 (d, J=8.5 Hz, 2 H), 6.86 (d, J=3.4 Hz, 1 H), 4.36 (q, J=8.2 Hz, 2 H), 4.17-4.26 (m, 3 H), 3.83 (s, 3 H), 2.47 (s, 3 H), 2.15-2.28 (m, 1 H), 1.93-2.13 (m, 3 H), 1.80-1.93 (m, 2 H).

Workup

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

Sources & evidence

ORD record
ord-faa6e45cf62040668f44357aa23b6ebd
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

Loading…