Diethyl Ether → 1-Methyl-3-[4-[8-(morpholin-4-yl)-2-[2-(quinolin-2-yl)ethyl]imidazo[1,2-b]pyridazin-3-yl]phenyl]-4,5-dihydro-1H-1,2,4-triazol-5-one

HRID 718648Notes

Reaction equation

HRID 718648 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:26]4[N:27]=[CH:28][CH:29]=[C:30]([N:31]5[CH2:36][CH2:35][O:34][CH2:33][CH2:32]5)[C:25]4=[N:24][C:23]=3[CH2:37][CH2:38][C:39]3[CH:48]=[CH:47][C:46]4[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=4)[N:40]=3)=[CH:18][CH:17]=2)=[N:3]1.CCOCC>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:26]4[N:27]=[CH:28][CH:29]=[C:30]([N:31]5[CH2:32][CH2:33][O:34][CH2:35][CH2:36]5)[C:25]4=[N:24][C:23]=3[CH2:37][CH2:38][C:39]3[CH:48]=[CH:47][C:46]4[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=4)[N:40]=3)=[CH:20][CH:21]=2)=[N:3]1

Participants

4

Reactant 2

HCID 3283Diethyl EtherHCID 1239382441-Methyl-3-[4-[8-(morpholin-4-yl)-2-[2-(quinolin-2-yl)ethyl]imidazo[1,2-b]pyridazin-3-yl]phenyl]-4-[[2-(trimethylsilyl)ethoxy]methyl]-4,5-dihydro-1H-1,2,4-triazol-5-one

Product 1

HCID 1369420711-Methyl-3-[4-[8-(morpholin-4-yl)-2-[2-(quinolin-2-yl)ethyl]imidazo[1,2-b]pyridazin-3-yl]phenyl]-4,5-dihydro-1H-1,2,4-triazol-5-one

Reagents, catalysts & solvents 1

HCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Conditions

Temperature
70 °C

Procedure

A solution of compound 51e (0.20 g, 0.29 mmol) in TFA/DCM (1:3 v/v, 5 mL) was stirred overnight at rt. The mixture was concentrated under reduced pressure, and the residue obtained was treated with Et2O (10 mL). The solids formed were collected by filtration, washed with Et2O (2×20 mL), and treated with MeOH (5 mL) and DIEA (0.5 mL). The resulting solution was stirred at 70° C. for 30 min and allowed to cool to rt. The solids formed were collected by filtration and washed with Et2O (2×20 mL) to obtain the title compound 78 as a white solid. 1H-NMR (300 MHz, DMSO-d6) δ (ppm): 12.30 (s, 1H), 8.21 (d, J=8.7 Hz, 1H), 8.08 (d, J=5.4 Hz, 1H), 7.85-7.92 (m, 4H), 7.76-7.67 (m, 3H), 7.55-7.50 (m, 1H), 7.41 (d, J=8.4 Hz, 1H), 6.34 (d, J=5.7 Hz, 1H), 3.92-3.85 (m, 4H), 3.78-3.70 (m, 4H), 3.39-3.34 (m, 7H). Mass Spectrum (LCMS, ESI pos.): Calcd. for C30H28N8O2: 533.2 (M+H). Found: 533.3.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customthe residue obtained
  3. customThe solids formed
  4. filtrationwere collected by filtration
  5. washwashed with Et2O (2×20 mL)
  6. additiontreated with MeOH (5 mL) and DIEA (0.5 mL)
  7. temperatureto cool to rt
  8. customThe solids formed
  9. filtrationwere collected by filtration
  10. washwashed with Et2O (2×20 mL)

Sources & evidence

ORD record
ord-d6196dd91a434f818f62e7bcdc04a1e9
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

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