Potassium Iodide → HCID 46864321, compound

HRID 1803259Notes

Reaction equation

HRID 1803259 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][CH:6]([C:14]1[NH:18][N:17]=[C:16]([NH:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[O:30][N:29]=[C:28]([CH3:31])[CH:27]=3)=[C:22]([O:32][CH3:33])[CH:21]=2)[N:15]=1)[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C=O)C>[F:13][C:10]1[CH:11]=[CH:12][C:7]([CH:6]2[CH2:5][CH2:4][CH2:3][CH2:2][N:18]3[N:17]=[C:16]([NH:19][C:20]4[CH:25]=[CH:24][C:23]([C:26]5[O:30][N:29]=[C:28]([CH3:31])[CH:27]=5)=[C:22]([O:32][CH3:33])[CH:21]=4)[N:15]=[C:14]23)=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 66859793HCID 66859793, compound

Product 1

HCID 46864321HCID 46864321, compoundYield 24.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of 5-(5-chloro-1-(4-fluorophenyl)pentyl)-N-(3-methoxy-4-(3-methylisoxazol-5-yl)phenyl)-1H-1,2,4-triazol-3-amine (580 mg, 1.234 mmol), potassium carbonate (682 mg, 4.94 mmol), and potassium iodide (410 mg, 2.468 mmol) in DMF (8 mL) was heated at 55° C. for 16 hrs. The solvent was removed in vacuo. The crude product was purified using reverse phase preparatory-HPLC (Column: Phenomenex Luna C18 30×100 mm, Solvent A=10 mM Ammonium Acetate in 95:5 water/ACN, Solvent B=10 mM Ammonium Acetate in 5:95 water/ACN. Flow rate: 40 ml/mM, 30-85% B, 25 min) to afford 9-(4-fluorophenyl)-N-(3-methoxy-4-(3-methylisoxazol-5-yl)phenyl)-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepin-2-amine (145 mg, 0.301 mmol, 24% yield). LC-MS (M+H)+ 434.3. 1H NMR (400 MHz, methanol-d4) δ ppm 7.67 (d, J=8.56 Hz, 1 H) 7.49 (d, J=2.01 Hz, 1 H) 7.23 (dd, J=8.56, 5.29 Hz, 2H) 7.09 (t, J=8.69 Hz, 2 H) 6.99 (dd, J=8.56, 2.01 Hz, 1 H) 4.35-4.44 (m, 1H) 4.15-4.35 (m, 2 H) 3.87 (s, 3 H) 2.30 (s, 3 H) 2.19-2.28 (m, 1 H) 2.00-2.10 (m, 1 H) 1.72-1.94 (m, 4 H).

Workup

  1. customThe solvent was removed in vacuo
  2. customThe crude product was purified
  3. customreverse phase preparatory-HPLC (Column: Phenomenex Luna C18 30×100 mm, Solvent A=10 mM Ammonium Acetate in 95:5 water/ACN, Solvent B=10 mM Ammonium Acetate in 5:95 water/ACN. Flow rate: 40 ml/mM, 30-85% B, 25 min)

Sources & evidence

ORD record
ord-4fc52a6af86648e4b4130a4d0d813e84
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

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