Ammonium Chloride → HCID 46183761, compound

HRID 2070904Notes

Reaction equation

HRID 2070904 reaction equation
C[O:2][C:3]1[CH:8]=[C:7]([C:9]([C:12]2[N:17]3[N:18]=[C:19]([NH:21][C:22]4[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=4)[N:20]=[C:16]3[CH:15]=[CH:14][CH:13]=2)(O)[CH3:10])[CH:6]=[CH:5][N:4]=1.C[Mg]Br.[Cl-].[NH4+]>O1CCCC1.O.C(OCC)(=O)C>[F:30][C:28]([F:29])([F:31])[C:25]1[CH:26]=[CH:27][C:22]([NH:21][C:19]2[N:20]=[C:16]3[CH:15]=[CH:14][CH:13]=[C:12]([CH:9]([C:7]4[CH:6]=[CH:5][NH:4][C:3](=[O:2])[CH:8]=4)[CH3:10])[N:17]3[N:18]=2)=[CH:23][CH:24]=1

Participants

7

Reactant 3

HCID 25517Ammonium ChlorideHCID 68588981HCID 68588981, compoundHCID 178418573HCID 178418573, compound2×

Product 1

HCID 46183761HCID 46183761, compoundYield 93%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

1-(2-Methoxypyridin-4-yl)-1-(2-(4-(trifluoromethyl)phenylamino)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)ethanol. Methylmagnesium bromide (1.390 mL, 4.17 mmol, 3 M solution in diethyl ether) was added dropwise to a stirred solution of (2-methoxypyridin-4-yl)(2-(4-(trifluoromethyl)phenylamino)-[1,2,4]triazolo[1,5-c]pyridin-5-yl)methanone (0.431 g, 1.043 mmol) in tetrahydrofuran (20 mL) at 0° C. under nitrogen. The reaction instantly became red-colored upon addition of the methylmagnesium bromide but then became more yellow-colored. The resulting mixture was stirred at 0° C. under nitrogen for 50 min. Saturated aqueous ammonium chloride (2 mL) was added to quench the reaction. The resulting mixture was diluted with water and ethyl acetate and shaken in a separatory funnel. The layers were separated. The organics were washed with brine, dried over magnesium sulfate, filtered, and concentrated on a rotary evaporator. The residue was dissolved in dichloromethane and purified using flash chromatography (Biotage) (20-90% ethyl acetate in hexane) to give the desired product (0.417 g, 0.971 mmol, 93% yield) as a yellow foam-solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 10.01 (s, 1H), 8.06 (d, J=5.47 Hz, 1H), 7.74 (dd, J=7.42, 8.59 Hz, 1H), 7.61 (dd, J=1.17, 8.98 Hz, 1H), 7.50-7.59 (m, 4H), 7.47 (dd, J=1.17, 7.42 Hz, 1H), 6.94 (d, J=0.78 Hz, 1H), 6.86 (dd, J=1.56, 5.47 Hz, 1H), 6.44 (s, 1H), 3.82 (s, 3H), 2.03 (s, 3H); 19F NMR (376 MHz, DMSO-d6) δ (ppm)-60.20 (s, 3F); MS (ESI) m/z 430.3 [M+H]+.

Workup

  1. customThe reaction
  2. customto quench
  3. customthe reaction
  4. stirringshaken in a separatory funnel
  5. customThe layers were separated
  6. washThe organics were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated on a rotary evaporator
  10. dissolutionThe residue was dissolved in dichloromethane
  11. custompurified

Sources & evidence

ORD record
ord-688295252e3844a7ba7bd33a449baa5e
Source dataset
uspto-grants-2012_10
Patent number
US08299056B2

Reaction notes

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