Trifluoroacetic acid → Trifluoroacetic acid

HRID 872253Notes

Reaction equation

HRID 872253 reaction equation
Br[CH:2]([CH3:11])[C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=O.[CH3:12][C:13]1[N:18]2[N:19]=[C:20]([C:22]3[CH:27]=[CH:26][N:25]=[C:24]([NH2:28])[CH:23]=3)[N:21]=[C:17]2[C:16]([CH3:29])=[N:15][CH:14]=1.C(N(C(C)C)C(C)C)C.[F:39][C:40]([F:45])([F:44])[C:41]([OH:43])=[O:42]>CCO.ClCCl>[CH3:12][C:13]1[N:18]2[N:19]=[C:20]([C:22]3[CH:27]=[CH:26][N:25]4[C:2]([CH3:11])=[C:3]([C:5]5[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=5)[N:28]=[C:24]4[CH:23]=3)[N:21]=[C:17]2[C:16]([CH3:29])=[N:15][CH:14]=1.[C:41]([OH:43])([C:40]([F:45])([F:44])[F:39])=[O:42]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 164522-BromopropiophenoneHCID 81531DiisopropylethylamineHCID 71151950HCID 71151950, compound

Product 2

HCID 6422Trifluoroacetic acidYield 18.5%HCID 71153072HCID 71153072, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

2-bromo-1-phenylpropan-1-one (0.032 ml, 0.208 mmol) was added to a solution of 4-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)pyridin-2-amine (0.025 mg, 0.104 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.056 ml, 0.312 mmol) in EtOH (2.5 mL) and the mixture was heated under standard microwave conditions at 110° C. for 4 hours. LC/MS analysis of the reaction mixture indicates reaction completion. The reaction mixture was concentrated in vacuo. The crude product was purified by flash chromatography (silica gel; 30-100% EtOAc/hexanes) to afford a yellow solid. The purified product was dissolved in 5 mL of a 1:1 solution of dichloromethane and trifluoroacetic acid. This mixture was allowed to stir overnight at room temperature. The volatiles were removed in vacuo to give 5,8-dimethyl-2-(3-methyl-2-phenylimidazo[1,2-a]pyridin-7-yl)-[1,2,4]triazolo[1,5-a]pyrazine, 2 TFA (0.0112 g, 0.019 mmol, 18.5% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.55 (d, J=7.5 Hz, 1H), 8.40 (s, 1H), 8.08 (s, 1H), 7.87 (d, J=7.0 Hz, 2H), 7.78 (dd, J=7.0, 1.8 Hz, 1H), 7.53 (t, J=7.7 Hz, 2H), 7.42 (d, J=7.3 Hz, 1H), 2.87 (s, 3H), 2.78 (s, 3H), 2.74 (s, 3H), LC/MS: (Method 2) Anal. Calcd. for [M+H]+C21H19N6: 355.16. Found: 355.18.

Workup

  1. customreaction completion
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customThe crude product was purified by flash chromatography (silica gel; 30-100% EtOAc/hexanes)
  4. customto afford a yellow solid
  5. customThe volatiles were removed in vacuo

Sources & evidence

ORD record
ord-9273f2debf2b4398a662e98db872cad1
Source dataset
uspto-grants-2015_03
Patent number
US08975276B2

Reaction notes

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