Sodium Iodide → N-(3-fluoro-4-(5-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 1803291Notes

Reaction equation

HRID 1803291 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[C:35]([CH3:36])=[N:34][CH:33]=[N:32]3)=[C:27]([F:37])[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:37][C:27]1[CH:26]=[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:30]=[CH:29][C:28]=1[N:31]1[C:35]([CH3:36])=[N:34][CH:33]=[N:32]1

Participants

4

Reactant 2

HCID 5238Sodium IodideHCID 668594305-(5-chloro-1-(4-(2,2,2-trifluoroethoxy)phenyl)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 46864358N-(3-fluoro-4-(5-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 39.2%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of 5-(5-chloro-1-(4-(2,2,2-trifluoroethoxy)phenyl)pentyl)-N-(3-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine (2.11 g, 3.92 mmol), sodium iodide (2.94 g, 19.6 mmol), and diisoproplylethylamine (0.685 mL, 3.92 mmol) in acetone (30 mL) was heated in a sealed vessel at 100° C. for 12 h. The reaction was concentrated in vacuo. The crude product was purified using silica gel column chromatography (50% EtOAc/chloroform) to afford 770 mg (38% yield) of the titled compound as an off-white solid. This material was recrystallized from EtOH (20 mL) to afford 424 mg (22% yield) of the titled compound as a crystalline white solid. LC-MS (M+H)+ 502.5. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.96 (s, 1 H), 7.67 (dd, J=12.8, 2.4 Hz, 1H), 7.24 (t, J=8.5 Hz, 1 H), 7.13 (d, J=8.9 Hz, 2 H), 7.02 (dd, J=9.2, 2.1 Hz, 1 H), 7.00 (s, 1 H), 6.93-6.98 (m, 2H), 4.36 (q, J=8.2 Hz, 2 H), 4.29 (dd, J=8.5, 2.1 Hz, 1 H), 4.22-4.27 (m, 2 H), 2.40 (s, 3 H), 2.17-2.30 (m, 1 H), 2.04-2.13 (m, 1 H), 1.82-2.02 (m, 4 H).

Workup

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

Sources & evidence

ORD record
ord-e927b466774743dcb473038bc3e1193e
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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