Trifluoroacetic acid → 1-Methyl-3-[4-[8-(morpholin-4-yl)-2-[2-(quinolin-2-yl)ethyl]imidazo[1,2-a]pyrazin-5-yl]phenyl]-4,5-dihydro-1H-1,2,4-triazol-5-one

HRID 1772609Notes

Reaction equation

HRID 1772609 reaction equation
[CH3:1][N:2]1[C:6](=[O:7])[N:5](COCC[Si](C)(C)C)[C:4]([C:16]2[CH:21]=[CH:20][C:19]([C:22]3[N:27]4[CH:28]=[C:29]([CH2:31][CH2:32][C:33]5[CH:42]=[CH:41][C:40]6[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=6)[N:34]=5)[N:30]=[C:26]4[C:25]([N:43]4[CH2:48][CH2:47][O:46][CH2:45][CH2:44]4)=[N:24][CH:23]=3)=[CH:18][CH:17]=2)=[N:3]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:1][N:2]1[C:6](=[O:7])[NH:5][C:4]([C:16]2[CH:17]=[CH:18][C:19]([C:22]3[N:27]4[CH:28]=[C:29]([CH2:31][CH2:32][C:33]5[CH:42]=[CH:41][C:40]6[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=6)[N:34]=5)[N:30]=[C:26]4[C:25]([N:43]4[CH2:44][CH2:45][O:46][CH2:47][CH2:48]4)=[N:24][CH:23]=3)=[CH:20][CH:21]=2)=[N:3]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 1231892491-Methyl-3-[4-[8-(morpholin-4-yl)-2-[2-(quinolin-2-yl)ethyl]imidazo[1,2-a]pyrazin-5-yl]phenyl]-4-[[2-(trimethylsilyl)ethoxy]methyl]-4,5-dihydro-1H-1,2,4-triazol-5-one

Product 1

HCID 1363106411-Methyl-3-[4-[8-(morpholin-4-yl)-2-[2-(quinolin-2-yl)ethyl]imidazo[1,2-a]pyrazin-5-yl]phenyl]-4,5-dihydro-1H-1,2,4-triazol-5-oneYield 25.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of compound 10e (200 mg, 0.290 mmol) in DCM (6 mL) was added TFA (2 mL) dropwise with stirring at 0° C. The resulting solution was stirred at rt overnight. The reaction was quenched with MeOH (10 mL). The resulting solids were collected by filtration and washed with Et2O, and then suspended in MeOH (10 mL) and DIPEA (0.5 mL). The mixture was stirred at 70° C. for 30 min. After cooling to rt, the solids were collected by filtration and washed with Et2O to obtain the title compound 33 as a light yellow solid (39.4 mg, 24% yield). 1H-NMR (300 MHz, DMSO-d6) δ (ppm): 12.36 (s, 1H), 8.28 (d, J=8.4 Hz, 1H), 7.95-7.88 (m, 4H), 7.75-7.68 (m, 4H), 7.58-7.49 (m, 2H), 7.41 (s, 1H), 4.20-4.08 (m, 4H), 3.75-3.65 (m, 4H), 3.41 (s, 3H), 3.40-3.25 (m, 4H). Mass Spectrum (LCMS, ESI pos.): Calcd. for C30H28N8O2: 533.2 (M+H). Found 533.2.

Workup

  1. stirringThe resulting solution was stirred at rt overnight
  2. customThe reaction was quenched with MeOH (10 mL)
  3. filtrationThe resulting solids were collected by filtration
  4. washwashed with Et2O
  5. stirringThe mixture was stirred at 70° C. for 30 min
  6. temperatureAfter cooling to rt
  7. filtrationthe solids were collected by filtration
  8. washwashed with Et2O

Sources & evidence

ORD record
ord-ae152d60eb024d52ad2b1070cd7e2468
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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