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

HRID 1803331Notes

Reaction equation

HRID 1803331 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]=[C:28]([O:30][CH3:31])[C:27]([N:32]3[CH:36]=[N:35][C:34]([CH3:37])=[N:33]3)=[CH:26][C:25]=2[F:38])[N:19]=1)[C:7]1[CH:12]=[CH:11][C:10]([O:13][C:14]([F:17])([F:16])[F:15])=[CH:9][CH:8]=1.[I-].[Na+]>CC(C)=O>[F:38][C:25]1[CH:26]=[C:27]([N:32]2[CH:36]=[N:35][C:34]([CH3:37])=[N:33]2)[C:28]([O:30][CH3:31])=[CH:29][C:24]=1[NH:23][C:20]1[N:19]=[C:18]2[CH:6]([C:7]3[CH:12]=[CH:11][C:10]([O:13][C:14]([F:17])([F:16])[F:15])=[CH:9][CH:8]=3)[CH2:5][CH2:4][CH2:3][CH2:2][N:22]2[N:21]=1

Participants

4

Reactant 2

HCID 5238Sodium IodideHCID 668588375-(5-chloro-1-(4-(trifluoromethoxy)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 58110088N-(2-fluoro-5-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-9-(4-(trifluoromethoxy)phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-amineYield 54.8%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of 5-(5-chloro-1-(4-(trifluoromethoxy)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 (820 mg, 1.480 mmol), sodium iodide (1.11 g, 7.40 mmol), and diisoproplylethylamine (0.256 mL, 1.48 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 420 mg (52% yield) of the titled compound as an off-white solid. LC-MS (M+H)+ 518.3. 1H NMR (500 MHz, CHLOROFORM-4) δ ppm 8.55 (s, 1 H), 8.09 (d, J=7.6 Hz, 1 H), 7.48 (d, J=11.6 Hz, 1 H), 7.19-7.26 (m, 4 H), 6.83 (d, J=3.4 Hz, 1 H), 4.18-4.35 (m, 3 H), 3.81 (s, 3 H), 2.47 (s, 3 H), 2.16-2.24 (m, 1 H), 1.96-2.15 (m, 3 H), 1.80-1.95 (m, 2 H).

Workup

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

Sources & evidence

ORD record
ord-ed0b3b4d3082473881d0415bd17a3e44
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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