Triethylamine → 5-(2-fluorophenyl)-7-methyl-4-(1-methyl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl)imidazo[5,1-f][1,2,4]triazine

HRID 2284437Notes

Reaction equation

HRID 2284437 reaction equation
C(N(CC)CC)C.Br.[CH3:9][N:10]1[C:14]2[CH2:15][NH:16][CH2:17][CH2:18][C:13]=2[CH:12]=[N:11]1.[F:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]1[N:27]=[C:28]([CH3:40])[N:29]2[C:34]=1[C:33](N1C=NC=N1)=[N:32][CH:31]=[N:30]2>ClCCl>[F:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]1[N:27]=[C:28]([CH3:40])[N:29]2[C:34]=1[C:33]([N:16]1[CH2:17][CH2:18][C:13]3[CH:12]=[N:11][N:10]([CH3:9])[C:14]=3[CH2:15]1)=[N:32][CH:31]=[N:30]2

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1176784165-(2-fluorophenyl)-7-methyl-4-(1H-1,2,4-triazol-1-yl)imidazo[5,1-f][1,2,4]triazineHCID 1317323451-methyl-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine, hydrobromide salt

Product 1

HCID 917995295-(2-fluorophenyl)-7-methyl-4-(1-methyl-1,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridin-6-yl)imidazo[5,1-f][1,2,4]triazine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

Triethylamine (0.510 mL, 3.66 mmol) and C9 (0.333 g, 1.58 mmol) were added to a solution of C6 (0.360 g, 1.22 mmol) in dichloromethane (10 mL), and the reaction mixture was heated at 40° C. for 18 hours. The mixture was then washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. Purification was effected first via silica gel chromatography (Gradient: 0% to 100% ethyl acetate in heptane), then by reversed phase HPLC (Column: Phenomenex Gemini C18, 5 μm; Mobile phase A: 0.1% ammonium hydroxide in water; Mobile phase B: 0.1% ammonium hydroxide in methanol; Gradient: 5% to 100% B). The product was obtained as a solid. Yield: 202 mg, 0.556 mmol, 46%. LCMS m/z 364.2 [M+H]+. 1H NMR (400 MHz, CD3OD) δ 7.98 (s, 1H), 7.63 (ddd, J=7.6, 7.5, 1.8 Hz, 1H), 7.52 (dddd, J=8.3, 7.5, 5.2, 1.8 Hz, 1H), 7.35 (ddd, J=7.6, 7.5, 1.1 Hz, 1H), 7.22 (br ddd, J=10.0, 8.3, 1.0 Hz, 1H), 7.16 (br s, 1H), 4.45 (br s, 2H), 3.76-3.84 (m, 2H), 3.43 (s, 3H), 2.67 (s, 3H), 2.35-2.41 (m, 2H).

Workup

  1. washThe mixture was then washed with saturated aqueous sodium chloride solution
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification
  6. customThe product was obtained as a solid

Sources & evidence

ORD record
ord-6d8e127b08294b439c6d6a14a5103181
Source dataset
uspto-grants-2015_09
Patent number
US09145427B2

Reaction notes

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