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

HRID 1803285Notes

Reaction equation

HRID 1803285 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]=[CH:29][C:28]([N:31]3[CH:35]=[C:34]([Cl:36])[N:33]=[CH:32]3)=[C:27]([O:37][CH3:38])[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>[Cl:36][C:34]1[N:33]=[CH:32][N:31]([C:28]2[CH:29]=[CH:30][C:25]([NH:24][C:21]3[N:20]=[C:19]4[CH:6]([C:7]5[CH:12]=[CH:11][C:10]([O:13][CH2:14][C:15]([F:16])([F:18])[F:17])=[CH:9][CH:8]=5)[CH2:5][CH2:4][CH2:3][CH2:2][N:23]4[N:22]=3)=[CH:26][C:27]=2[O:37][CH3:38])[CH:35]=1

Participants

4

Reactant 2

HCID 5238Sodium IodideHCID 668594105-(5-chloro-1-(4-(2,2,2-trifluoroethoxy)phenyl)pentyl)-N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-1H-1,2,4-triazol-3-amine

Product 1

HCID 58110027N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-9-(4-(2,2,2-trifluoroethoxy)phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-amineYield 15%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of 5-(5-chloro-1-(4-(2,2,2-trifluoroethoxy)phenyl)pentyl)-N-(4-(4-chloro-1H-imidazol-1-yl)-3-methoxyphenyl)-1H-1,2,4-triazol-3-amine (2.02 g, 3.54 mmol), sodium iodide (2.65 g, 17.7 mmol), and diisoproplylethylamine (0.618 mL, 3.54 mmol) in acetone (25 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 281 mg (15% yield) of the titled compound as an off-white solid. LC-MS (M+H)+ 533.2. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.51 (d, J=1.5 Hz, 1H), 7.41 (d, J=2.4 Hz, 1 H), 7.14 (m, J=8.9 Hz, 2 H), 7.09 (d, J=8.5 Hz, 1 H), 7.02 (d, J=1.5 Hz, 1 H), 6.95 (m, J=8.9 Hz, 2 H), 6.84 (dd, J=8.5, 2.1 Hz, 1 H), 6.66 (s, 1 H), 4.36 (q, J=8.1 Hz, 2 H), 4.20-4.27 (m, 3 H), 3.80 (s, 3 H), 2.16-2.29 (m, 1H), 2.05-2.13 (m, 1 H), 1.92-2.03 (m, 2 H), 1.83-1.90 (m, 2 H).

Workup

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

Sources & evidence

ORD record
ord-c58184dc04ec40ef9605eaa16c1a616e
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

Loading…